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Spinello Z, Besharat ZM, Mainiero F, Rughetti A, Masuelli L, Ferretti E, Catanzaro G. MiR-326: Role and significance in brain cancers. Noncoding RNA Res 2025; 12:56-64. [PMID: 40115178 PMCID: PMC11925037 DOI: 10.1016/j.ncrna.2025.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 02/17/2025] [Accepted: 02/18/2025] [Indexed: 03/23/2025] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that act as critical regulators of gene expression by repressing mRNA translation. The role of miRNAs in cell physiology spans from cell cycle control to cell proliferation and differentiation, both during development and in adult tissues. Accordingly, dysregulated expression of miRNAs has been reported in several diseases, including cancer, where miRNAs can act as oncogenes or oncosuppressors. Of note, miRNA signatures are also under investigation for classification, diagnosis, and prognosis of cancer patients. Brain tumours are primarily associated with poor prognosis and high mortality, highlighting an urgent need for novel diagnostic, prognostic, and therapeutic tools. Among miRNAs investigated in brain tumours, miR-326 has been shown to act as a tumour suppressor in adult and paediatric brain cancers. In this review, we describe the role of miR-326 in malignant as well as benign cancers originating from brain tissue. In addition, since miR-326 expression can be regulated by other non-coding RNA species, adding a further layer of regulation in the cancer-promoting axis, we discuss this miRNA's role in targeted therapy for brain cancers.
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Affiliation(s)
- Zaira Spinello
- Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy
| | - Zein Mersini Besharat
- Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy
| | - Fabrizio Mainiero
- Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy
| | - Aurelia Rughetti
- Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy
| | - Laura Masuelli
- Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy
| | - Elisabetta Ferretti
- Department of Experimental Medicine, Sapienza University of Rome, 00161, Rome, Italy
| | - Giuseppina Catanzaro
- Department of Life Science, Health, and Health Professions, Link Campus University, 00165, Rome, Italy
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Ma FC, Zhang GL, Chi BT, Tang YL, Peng W, Liu AQ, Chen G, Gao JB, Wei DM, Ge LY. Blood-based machine learning classifiers for early diagnosis of gastric cancer via multiple miRNAs. World J Gastrointest Oncol 2025; 17:103679. [DOI: 10.4251/wjgo.v17.i4.103679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/16/2025] [Accepted: 02/11/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Early screening methods for gastric cancer (GC) are lacking; therefore, the disease often progresses to an advanced stage when patients first start to exhibit typical symptoms. Endoscopy and pathological biopsy remain the primary diagnostic approaches, but they are invasive and not yet widely applicable for early population screening. miRNA is a highly conserved type of RNA that exists stably in plasma. Dysfunction of miRNA is linked to tumorigenesis and progression, indicating that individual miRNAs or combinations of multiple miRNAs may serve as potential biomarkers.
AIM To identify effective plasma miRNA biomarkers and investigate the clinical value of combining multiple miRNAs for early detection of GC.
METHODS Plasma samples from multiple centres were collected. Differentially expressed genes among healthy controls, early-stage GC patients, and advanced-stage GC patients were identified through small RNA sequencing (sRNA-seq) and validated via real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). A Wilcoxon signed-rank test was used to investigate the differences in miRNAs. Sequencing datasets of GC serum samples were retrieved from the Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas databases, and a multilayer perceptron-artificial neural network (MLP-ANN) model was constructed for the key risk miRNAs. The pROC package was used to assess the discriminatory efficacy of the model.
RESULTS Plasma samples of 107 normal, 71 early GC and 97 advanced GC patients were obtained from three centres, and serum samples of 8443 normal and 1583 GC patients were obtained from the GEO database. The sRNA-seq and RT-qPCR experiments revealed that miR-452-5p, miR-5010-5p, miR-27b-5p, miR-5189-5p, miR-552-5p and miR-199b-5p were significantly increased in early GC patients compared with healthy controls and in advanced GC patients compared with early GC patients (P < 0.05). An MLP-ANN model was constructed for the six key miRNAs. The area under the curve (AUC) within the training cohort was 0.983 [95% confidence interval (CI): 0.980–0.986]. In the two validation cohorts, the AUCs were 0.995 (95%CI: 0.987 to nearly 1.000) and 0.979 (95%CI: 0.972–0.986), respectively.
CONCLUSION Potential miRNA biomarkers, including miR-452-5p, miR-5010-5p, miR-27b-5p, miR-5189-5p, miR-552-5p and miR-199b-5p, were identified. A GC classifier based on these miRNAs was developed, benefiting early detection and population screening.
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Affiliation(s)
- Fu-Chao Ma
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Guan-Lan Zhang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Bang-Teng Chi
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Yu-Lu Tang
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Wei Peng
- Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Ai-Qun Liu
- Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Gang Chen
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Jin-Biao Gao
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Dan-Ming Wei
- Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Lian-Ying Ge
- Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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Pant A, Moar K, Arora TK, Dakal TC, Ranga V, Sharma NK, Maurya PK. Deciphering the role of circulating miRNAs in the etiology and pathophysiology of endometriosis: An updated compiled review. Exp Cell Res 2025; 446:114482. [PMID: 40015501 DOI: 10.1016/j.yexcr.2025.114482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 01/28/2025] [Accepted: 02/23/2025] [Indexed: 03/01/2025]
Abstract
Endometriosis is characterized by the presence of endometrial tissue outside of the uterus. It is a benign chronic condition with incapacitating symptoms like infertility and pelvic pain. Endometriosis has a detrimental impact on the reproductive health of women, placing a heavy financial strain on the medical system. It is a multifactorial disorder governed by numerous mechanisms or risk factors that contribute to the pathologies of the disease. With limitations in diagnostics techniques, it is challenging to detect the disease at an initial stage. In around 1 % of endometriotic patients malignant state may reach, leading to severe consequences. To overcome such challenges, at present, numerous circulating miRNAs have been studied in plasma or serum samples from patients with endometriosis to develop a non-invasive diagnostic biomarker-based tool to identify the disease early. Our review compiles the miRNAs in bodily fluids that are linked with endometriosis-related mechanisms, which may serve as a potential biomarker. Some of these mechanisms are common in both cancer and endometriosis. Additionally, we have also emphasised the miRNAs with a putative role in cancer development and progression that could be used as a biomarker. This may further aid in protecting the 1 % of affected females from ovarian, breast, and in some cases endometrial cancer. We have come across several miRNAs associated with multiple mechanisms associated with endometriosis. miR-199a and miRNAs-let-7 family are some of the most common miRNAs that assist in multiple mechanisms such as cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition. Strategic planning and additional investigation into the identified miRNAs would make them a viable therapeutic target for the optimal management of endometriosis.
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Affiliation(s)
- Anuja Pant
- Department of Biochemistry, Central University of Haryana, Mahendergarh, India, 123031
| | - Kareena Moar
- Department of Biochemistry, Central University of Haryana, Mahendergarh, India, 123031
| | - Taruna K Arora
- Reproductive Biology and Maternal Child Health Division, Indian Council of Medical Research, New Delhi, 110029, India
| | - Tikam Chand Dakal
- Genome and Computational Biology Lab, Department of Biotechnology, Mohanlal Sukhadia University, Udaipur, 313001, Rajasthan, India
| | - Vipin Ranga
- DBT-NECAB, Assam Agricultural University, Jorhat, 785013, Assam, India
| | - Narendra Kumar Sharma
- Department of Bioscience and Biotechnology, Banasthali Vidyapith, Tonk, 304022, Rajasthan, India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendergarh, India, 123031.
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Chuang YT, Yen CY, Tang JY, Chang FR, Tsai YH, Wu KC, Chien TM, Chang HW. The modulation of immune cell death in connection to microRNAs and natural products. Front Immunol 2024; 15:1425602. [PMID: 39759512 PMCID: PMC11695430 DOI: 10.3389/fimmu.2024.1425602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 11/27/2024] [Indexed: 01/07/2025] Open
Abstract
Immunogenic cell death (ICD) spatiotemporally regulates damage-associated molecular patterns (DAMPs) derived from dying cancer cells to signal the immune response. Intriguingly, these DAMPs and cytokines also induce cellular responses in non-immune cells, particularly cancer cells. Several ICD-modulating natural products and miRNAs have been reported to regulate the DAMP, cytokine, and cell death responses, but they lack systemic organization and connection. This review summarizes the impacts of natural products and miRNAs on the DAMP and cytokine responses and cancer cell death responses (apoptosis, autophagy, ferroptosis, necroptosis, and pyroptosis). We establish the rationale that ICD inducers of natural products have modulating effects on miRNAs, targeting DAMPs and cytokines for immune and cancer cell death responses. In conclusion, DAMP, cytokine, and cell death responses are intricately linked in cancer cells, and they are influenced by ICD-modulating natural products and miRNAs.
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Affiliation(s)
- Ya-Ting Chuang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yu Yen
- School of Dentistry, Taipei Medical University, Taipei, Taiwan
- Department of Oral and Maxillofacial Surgery, Chi-Mei Medical Center, Tainan, Taiwan
| | - Jen-Yang Tang
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Fang-Rong Chang
- Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hong Tsai
- Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung, Taiwan
| | - Kuo-Chuan Wu
- Department of Computer Science and Information Engineering, National Pingtung University, Pingtung, Taiwan
| | - Tsu-Ming Chien
- School of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Urology, Kaohsiung Gangshan Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsueh-Wei Chang
- Department of Biomedical Science and Environmental Biology, PhD Program in Life Sciences, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
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Arab I, Lim SG, Suk K, Lee WH. LINC01270 Regulates the NF-κB-Mediated Pro-Inflammatory Response via the miR-326/LDOC1 Axis in THP-1 Cells. Cells 2024; 13:2027. [PMID: 39682774 DOI: 10.3390/cells13232027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 11/28/2024] [Accepted: 12/06/2024] [Indexed: 12/18/2024] Open
Abstract
Long intergenic noncoding (LINC)01270 is a 2278 bp transcript belonging to the intergenic subset of long noncoding (lnc)RNAs. Despite increased reports of LINC01270's involvement in different diseases, evident research on its effects on inflammation is yet to be achieved. In the present study, we investigated the potential role of LINC01270 in modulating the inflammatory response in the human monocytic leukemia cell line THP-1. Lipopolysaccharide treatment upregulated LINC01270 expression, and siRNA-mediated suppression of LINC01270 enhanced NF-κB activity and the subsequent production of cytokines IL-6, IL-8, and MCP-1. Interestingly, the knockdown of LINC01270 downregulated expression of leucine zipper downregulated in cancer 1 (LDOC1), a novel NF-κB suppressor. An analysis of the LINC01270/micro-RNA (miRNA)/protein interactome profile identified miR-326 as a possible mediator. Synthetic RNA agents that perturb the interaction among LINC01270, miR-326, and LDOC1 mRNA mitigated the changes caused by LINC01270 knockdown in THP-1 cells. Additionally, a luciferase reporter assay in HEK293 cells further confirmed that LINC01270 knockdown enhances NF-κB activation, while its overexpression has the opposite effect. This study provides insight into LINC01270's role in modulating inflammatory responses to lipopolysaccharide stimulation in THP-1 cells via the miR-326/LDOC1 axis, which negatively regulates NF-κB activation.
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Affiliation(s)
- Imene Arab
- School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
- BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Su-Geun Lim
- School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
- BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Kyoungho Suk
- Brain Science & Engineering Institute, Kyungpook National University, Daegu 41944, Republic of Korea
- Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
- BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea
| | - Won-Ha Lee
- School of Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
- BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea
- Brain Science & Engineering Institute, Kyungpook National University, Daegu 41944, Republic of Korea
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Fang Y, Wu Y, Zhang X, Wei L, Liu L, Chen Y, Chen D, Xu N, Cao L, Zhu J, Chen M, Cheng Y, Sferra TJ, Yao M, Shen A, Peng J. miR-326 overexpression inhibits colorectal cancer cell growth and proteasome activity by targeting PNO1: unveiling a novel therapeutic intervention strategy. Sci Rep 2024; 14:24284. [PMID: 39414903 PMCID: PMC11484865 DOI: 10.1038/s41598-024-75746-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 10/08/2024] [Indexed: 10/18/2024] Open
Abstract
Proteasome inhibition emerges as a promising strategy for cancer prevention. PNO1, pivotal for colorectal cancer (CRC) progression, is involved in proteasome assembly in Saccharomyces cerevisiae. Hence, we aimed to explore the role of PNO1 in proteasome assembly and its up- and down-streams in CRC. Here, we demonstrated that PNO1 knockdown suppressed CRC cells growth, proteasome activities and assembly, as well as CDKN1B/p27Kip1 (p27) degradation. Moreover, p27 knockdown partially attenuated the inhibition of HCT116 cells growth by PNO1 knockdown. The up-stream studies of PNO1 identified miR-326 as a candidate miRNA directly targeting to CDS-region of PNO1 and its overexpression significantly down-regulated PNO1 protein expression, resulting in suppression of cell growth, decrease of proteasome activities and assembly, as well as increasing the stability of p27 in CRC cells. These findings indicated that miR-326 overexpression can suppress CRC cell growth, acting as an endogenous proteasome inhibitor by targeting PNO1.
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Affiliation(s)
- Yi Fang
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Yulun Wu
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Xinran Zhang
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Lihui Wei
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Liya Liu
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China
| | - Youqin Chen
- Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, 44106, USA
| | - Daxin Chen
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Nanhui Xu
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Liujin Cao
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Jie Zhu
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Mian Chen
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Ying Cheng
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Thomas J Sferra
- Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, 44106, USA
| | - Mengying Yao
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Aling Shen
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
| | - Jun Peng
- Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
- Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
- Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China.
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7
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Dong C, Yang L, Zhao G. Circ-PGAM1 Enhances Matrine Resistance of Non-Small Cell Lung Cancer via the miR-326/CXCR5 Axis. Cancer Biother Radiopharm 2024; 39:593-599. [PMID: 36576783 DOI: 10.1089/cbr.2022.0039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Background: Circular RNAs (circ-RNAs) have been demonstrated to influence initiation, drug resistance, and metastasis of tumors. However, the effects of circular-phosphoglycerate mutase 1 (circ-PGAM1) on matrine resistance in nonsmall cell lung cancer (NSCLC) remain unknown. Materials and Methods: The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine gene expression. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cell colony formation assays were used to evaluate NSCLC apoptosis and cell proliferation after indicated treatments, respectively. Results: circ-PGAM1 was upregulated in human NSCLC cell lines (H1299 and A549) compared with the human normal lung epithelial (BEAS-2B) cells. circ-PGAM1 overexpression reversed the matrine treatment-induced inhibition on proliferation of NSCLC cells (A549 and H1299) and rescued the matrine treatment-stimulated apoptosis of these cells. miR-326 was demonstrated to interact with circ-PGAM1. circ-PGAM1 knockdown enhanced the antitumor effect of matrine on NSCLC cell proliferation and apoptosis, which was reversed by miR-326 inhibition. The authors also identified CXCR5 as a key downstream target of miR-326 in A549 cells. Conclusions: circ-PGAM1 enhances matrine resistance of NSCLC cells through the miR-326/CXCR5 axis. The authors' findings provide new insights into NSCLC-targeted therapy.
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Affiliation(s)
- Caijun Dong
- Department of Thoracic Surgery, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Liangwei Yang
- Department of Cardiothoracic Surgery, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Guofang Zhao
- Department of Thoracic Surgery, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China
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Hedayati N, Mafi A, Farahani A, Hashemi M, Nabavi N, Alimohammadi M, Rahimzadeh P, Taheriazam A, Farahani N. The importance of the circRNA/Wnt axis in gliomas: Biological functions and clinical opportunities. Pathol Res Pract 2024; 261:155510. [PMID: 39116573 DOI: 10.1016/j.prp.2024.155510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 07/24/2024] [Accepted: 07/29/2024] [Indexed: 08/10/2024]
Abstract
Gliomas are among the most common cancers in the central nervous system, arising through various signaling pathways. One significant pathway is Wnt signaling, a tightly regulated process that plays a crucial role in gliomagenesis and development. The current study aims to explore the relationship between circular RNAs (circRNAs) and the Wnt/β-catenin signaling pathway in gliomas, considering the growing recognition of circRNAs in disease pathogenesis. A comprehensive review of recent research was conducted to investigate the roles of circRNAs in gliomas, focusing on their expression patterns and interactions with the Wnt signaling pathway. The analysis included studies examining circRNAs' function as microRNA sponges and their impact on glioma biology. The findings reveal that circRNAs are differentially expressed in gliomas and significantly influence the occurrence, growth, and metastasis of these tumors. Specifically, circRNAs interact with the Wnt signaling pathway, affecting glioma development and progression. This interaction highlights the importance of circRNAs in glioma pathophysiology. Understanding the regulatory network involving circRNAs and Wnt signaling offers valuable insights into glioma pathophysiology. CircRNAs hold promise as diagnostic and prognostic biomarkers and may serve as targets for novel therapeutic strategies in glioma treatment.
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Affiliation(s)
- Neda Hedayati
- School of Medicine, Iran University of Medical Science, Tehran, Iran
| | - Alireza Mafi
- Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Aryan Farahani
- Student Research Committee, Faculty of Medicine, Shahid Beheshti University of Medical sciences, Tehran, Iran
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Noushin Nabavi
- Independent Researcher, Victoria, British Columbia, Canada
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Payman Rahimzadeh
- Surgical Research Society (SRS), Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Najma Farahani
- Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran.
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An J, Shi J, Yang C, Luo J, Li Y, Ren J, Lv Y, Zhang Y. Regulation of tumorigenesis and ferroptosis in non-small cell lung cancer by a novel BBOX1-AS1/miR-326/PROM2 axis. Mol Cell Biochem 2024; 479:2143-2155. [PMID: 37639200 DOI: 10.1007/s11010-023-04837-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 08/14/2023] [Indexed: 08/29/2023]
Abstract
Dysregulation of long non-coding RNAs (lncRNAs) is associated with the tumorigenesis and ferroptosis of non-small cell lung cancer (NSCLC). BBOX1 antisense RNA 1 (BBOX1-AS1) functions as an oncogenic driver in NSCLC. Here, we aim to investigate the regulation effect and underlying mechanism of BBOX1-AS1 in NSCLC progression and ferroptosis. RNA expression was detected by quantitative real-time PCR (qRT-PCR), and protein expression was measured by immunoblotting. Cell growth was assessed by CCK-8 and colony formation assays. Transwell assay was applied to evaluate cell invasion and migration. RNA pull-down and dual-luciferase reporter assays were applied to verify the relationship between miR-326 and BBOX1-AS1 or prominin 2 (PROM2). The role of BBOX1-AS1 in NSCLC tumorigenicity was also analyzed by xenograft assays. Silencing BBOX1-AS1 or PROM2 impeded NSCLC cell growth, migration, and invasion. Silencing BBOX1-AS1 induced cell apoptosis and ferroptosis. BBOX1-AS1 up-regulated PROM2 expression, and re-expression of PROM2 reversed the effects of BBOX1-AS1 depletion on cell malignant phenotypes and ferroptosis. BBOX1-AS1 post-transcriptionally modulated PROM2 expression by sponging miR-326. MiR-326 was validated as a mediator of BBOX1-AS1 in regulating NSCLC cell malignant phenotypes and ferroptosis. Additionally, BBOX1-AS1 deficiency in vivo resulted in the suppression of xenograft tumor growth. Together, our study defines a novel BBOX1-AS1/miR-326/PROM2 axis in regulating NSCLC malignant progression and ferroptosis, offering new evidence for the oncogenic role of BBOX1-AS1 in NSCLC. These findings may provide a basis for the future usage of targeting BBOX1-AS1 in NSCLC treatment.
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MESH Headings
- Animals
- Female
- Humans
- Mice
- Carcinogenesis/genetics
- Carcinogenesis/metabolism
- Carcinoma, Non-Small-Cell Lung/pathology
- Carcinoma, Non-Small-Cell Lung/metabolism
- Carcinoma, Non-Small-Cell Lung/genetics
- Cell Line, Tumor
- Cell Proliferation
- Ferroptosis/genetics
- Gene Expression Regulation, Neoplastic
- Lung Neoplasms/pathology
- Lung Neoplasms/metabolism
- Lung Neoplasms/genetics
- Mice, Inbred BALB C
- Mice, Nude
- MicroRNAs/genetics
- MicroRNAs/metabolism
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- RNA, Neoplasm/genetics
- RNA, Neoplasm/metabolism
- RNA, Antisense
- gamma-Butyrobetaine Dioxygenase/genetics
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Affiliation(s)
- Jinlu An
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Jiang Shi
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China.
| | - Chao Yang
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Junfang Luo
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Yuning Li
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Jie Ren
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Yuanjun Lv
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
| | - Yang Zhang
- Department of Geriatric Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, China
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10
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Dai Q, Liu Y, Ding F, Guo R, Cheng G, Wang H. CircRNAs: A promising target for intervention regarding glycolysis in gastric cancer. Heliyon 2024; 10:e34658. [PMID: 39816354 PMCID: PMC11734058 DOI: 10.1016/j.heliyon.2024.e34658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 07/12/2024] [Accepted: 07/14/2024] [Indexed: 01/18/2025] Open
Abstract
Gastric cancer is characterized by a high incidence and mortality rate, with therapeutic efficacy currently constrained by substantial limitations. Aerobic glycolysis in cancer constitutes a pivotal aspect of the reprogramming of energy metabolism in tumor cells and profoundly influences the malignant progression of cancer. CircRNAs, serving as stable endogenous RNA, have been shown to regulate downstream targets by sponging miRNAs, which in turn are involved in the regulation of multiple malignant behaviors in a variety of cancers through the CircRNA-miRNA axis, suggesting that CircRNAs could be used as potential therapeutic targets for cancer. In recent years, it has been shown that some CircRNAs can be involved in the regulation of GC glycolysis, therefore, this paper summarizes the notable roles of some important CircRNAs in the regulation of GC glycolysis in recent years, which may be useful for our understanding of GC progression and the development of new therapeutic strategies.
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Affiliation(s)
- Qian Dai
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
| | - Yulin Liu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Fanghui Ding
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
| | - Rong Guo
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Gang Cheng
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Hua Wang
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
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11
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Farc O, Budisan L, Zaharie F, Țăulean R, Vălean D, Talvan E, Neagoe IB, Zănoagă O, Braicu C, Cristea V. Expression and Functional Analysis of Immuno-Micro-RNAs mir-146a and mir-326 in Colorectal Cancer. Curr Issues Mol Biol 2024; 46:7065-7085. [PMID: 39057062 PMCID: PMC11276483 DOI: 10.3390/cimb46070421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/27/2024] [Accepted: 06/28/2024] [Indexed: 07/28/2024] Open
Abstract
Micro-RNAs (miRNAs) are non-coding RNAs with importance in the development of cancer. They are involved in both tumor development and immune processes in tumors. The present study aims to characterize the behavior of two miRNAs, the proinflammatory miR-326-5p and the anti-inflammatory miR-146a-5p, in colorectal cancer (CRC), to decipher the mechanisms that regulate their expression, and to study potential applications. Tissue levels of miR-326-5p and miR-146a-5p were determined by qrt-PCR (real-time quantitative reverse transcription polymerase chain reaction) in 45 patients with colorectal cancer in tumoral and normal adjacent tissue. Subsequent bioinformatic analysis was performed to characterize the transcriptional networks that control the expression of the two miRNAs. The biomarker potential of miRNAs was assessed. The expression of miR-325-5p and miR-146a-5p was decreased in tumors compared to normal tissue. The two miRNAs are regulated through a transcriptional network, which originates in the inflammatory and proliferative pathways and regulates a set of cellular functions related to immunity, proliferation, and differentiation. The miRNAs coordinate distinct modules in the network. There is good biomarker potential of miR-326 with an AUC (Area under the curve) of 0.827, 0.911 sensitivity (Sn), and 0.689 specificity (Sp), and of the combination miR-326-miR-146a, with an AUC of 0.845, Sn of 0.75, and Sp of 0.89. The miRNAs are downregulated in the tumor tissue. They are regulated by a transcriptional network in which they coordinate distinct modules. The structure of the network highlights possible therapeutic approaches. MiR-326 and the combination of the two miRNAs may serve as biomarkers in CRC.
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Affiliation(s)
- Ovidiu Farc
- Research Center for Functional Genomics, Biomedicine and Translational Medicine “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (O.F.); (I.B.N.); (O.Z.); (C.B.)
| | - Liviuta Budisan
- Research Center for Functional Genomics, Biomedicine and Translational Medicine “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (O.F.); (I.B.N.); (O.Z.); (C.B.)
| | - Florin Zaharie
- Surgical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania; (F.Z.); (R.Ț.); (D.V.)
| | - Roman Țăulean
- Surgical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania; (F.Z.); (R.Ț.); (D.V.)
| | - Dan Vălean
- Surgical Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania; (F.Z.); (R.Ț.); (D.V.)
| | - Elena Talvan
- Faculty of Medicine Lucian Blaga, University of Sibiu, 550169 Sibiu, Romania;
| | - Ioana Berindan Neagoe
- Research Center for Functional Genomics, Biomedicine and Translational Medicine “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (O.F.); (I.B.N.); (O.Z.); (C.B.)
| | - Oana Zănoagă
- Research Center for Functional Genomics, Biomedicine and Translational Medicine “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (O.F.); (I.B.N.); (O.Z.); (C.B.)
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine “Iuliu Hatieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania; (O.F.); (I.B.N.); (O.Z.); (C.B.)
| | - Victor Cristea
- Immunology Department, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania;
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12
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Li P, Cui P, Yue Q, Xu Z, Liu Z. Exploring the potential biological significance of KDELR family genes in lung adenocarcinoma. Sci Rep 2024; 14:14820. [PMID: 38937522 PMCID: PMC11211404 DOI: 10.1038/s41598-024-65425-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 06/20/2024] [Indexed: 06/29/2024] Open
Abstract
The Lys-Asp-Glu-Leu receptor (KDELR) family genes play critical roles in a variety of biological processes in different tumors. Our study aimed to provide a comprehensive analysis of the potential roles of KDELRs in lung adenocarcinoma (LUAD). Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, as well as clinical samples, we conducted a series of analyses and validations using R software tools and various online resources. The results showed that KDELR family genes and proteins were highly expressed and associated with a poor prognosis of LUAD. Promoter hypomethylation and the competing endogenous RNA (ceRNA) network of PCAT6/hsa-miR-326/KDELR1 might be potential causes of aberrant KDELR1 overexpression in LUAD. Three key Transcription factors (TFs) (SPI1, EP300, and MAZ) and a TFs-miRNAs-KDELRs network (involving 11 TFs) might be involved in modulating KDELRs expression abnormalities. Gene Set Enrichment Analysis (GSEA) indicated enrichment of genes highly expressing KDELR1, KDELR2, and KDELR3 in MTORC1_SIGNALING, P53_PATHWAY, and ANGIOGENESIS. Negative correlations between KDELRs expression and CD8 + T cell infiltration, as well as CTLA-4 expression. Our multiple analyses suggested that the KDELRs are important signaling molecules in LUAD. These results provided novel insights for developing prognostic markers and novel therapies of LUAD.
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Affiliation(s)
- Peitong Li
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Pengfei Cui
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Qing Yue
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Zijun Xu
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Ziling Liu
- Cancer Center, The First Hospital of Jilin University, Changchun, China.
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13
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Han T, Liu Y, Zhou J, Guo J, Xing Y, Xie J, Bai Y, Wu J, Hu D. Development of an invasion score based on metastasis-related pathway activity profiles for identifying invasive molecular subtypes of lung adenocarcinoma. Sci Rep 2024; 14:1692. [PMID: 38243040 PMCID: PMC10799059 DOI: 10.1038/s41598-024-51681-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2023] [Accepted: 01/08/2024] [Indexed: 01/21/2024] Open
Abstract
The invasive capacity of lung adenocarcinoma (LUAD) is an important factor influencing patients' metastatic status and survival outcomes. However, there is still a lack of suitable biomarkers to evaluate tumor invasiveness. LUAD molecular subtypes were identified by unsupervised consistent clustering of LUAD. The differences in prognosis, tumor microenvironment (TME), and mutation were assessed among different subtypes. After that, the invasion-related gene score (IRGS) was constructed by genetic differential analysis, WGCNA analysis, and LASSO analysis, then we evaluated the relationship between IRGS and invasive characteristics, TME, and prognosis. The predictive ability of the IRGS was verified by in vitro experiments. Next, the "oncoPredict" R package and CMap were used to assess the potential value of IRGS in drug therapy. The results showed that LUAD was clustered into two molecular subtypes. And the C1 subtype exhibited a worse prognosis, higher stemness enrichment activity, less immune infiltration, and higher mutation frequency. Subsequently, IRGS developed based on molecular subtypes demonstrated a strong association with malignant characteristics such as invasive features, higher stemness scores, less immune infiltration, and worse survival. In vitro experiments showed that the higher IRGS LUAD cell had a stronger invasive capacity than the lower IRGS LUAD cell. Predictive analysis based on the "oncoPredict" R package showed that the high IRGS group was more sensitive to docetaxel, erlotinib, paclitaxel, and gefitinib. Among them, in vitro experiments verified the greater killing effect of paclitaxel on high IRGS cell lines. In addition, CMap showed that purvalanol-a, angiogenesis-inhibitor, and masitinib have potential therapeutic effects in the high IRGS group. In summary we identified and analyzed the molecular subtypes associated with the invasiveness of LUAD and developed IRGS that can efficiently predict the prognosis and invasive ability of the tumor. IRGS may be able to facilitate the precision treatment of LUAD to some extent.
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Affiliation(s)
- Tao Han
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China
| | - Yafeng Liu
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, 232001, China
- Affiliated Cancer Hospital, Anhui University of Science and Technology, Huainan, 232035, China
| | - Jiawei Zhou
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, 232001, China
| | - Jianqiang Guo
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, 232001, China
| | - Yingru Xing
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China
- Department of Clinical Laboratory, Anhui Zhongke Gengjiu Hospital, Hefei, China
| | - Jun Xie
- Affiliated Cancer Hospital, Anhui University of Science and Technology, Huainan, 232035, China
| | - Ying Bai
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China.
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, 232001, China.
| | - Jing Wu
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China.
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, 232001, China.
- Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan, 232001, China.
| | - Dong Hu
- School of Medicine, Anhui University of Science and Technology, Chongren Building, No 168, Taifeng St, Huainan, 232001, China.
- Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, 232001, China.
- Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan, 232001, China.
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14
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Saffari N, Rahgozar S, Faraji E, Sahin F. Plasma-derived exosomal miR-326, a prognostic biomarker and novel candidate for treatment of drug resistant pediatric acute lymphoblastic leukemia. Sci Rep 2024; 14:691. [PMID: 38184700 DOI: 10.1038/s41598-023-50628-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 12/22/2023] [Indexed: 01/08/2024] Open
Abstract
Acute lymphoblastic leukemia (ALL) is a cancer with high incidence rate in pediatrics and drug resistance is a major clinical concern for ALL treatment. The current study was designed to evaluate the role of exosomal miR-326 in diagnosis and treatment of children with B-ALL. Exosomes were isolated from plasma samples of 30 patients and B-ALL cell lines followed by characterization, using nanoparticle tracking analysis, immunoblotting assay and electron microscopy. qPCR showed significantly increased levels of miR-326 in patients exosomes compared with non-cancer controls (P < 0.05, AUC = 0.7500). Moreover, a comparison between the sensitive and drug resistant patients revealed a prognostic value for the exosomal miR326 (P < 0.05, AUC = 0.7755). Co-culture studies on drug resistant patient primary cells and B-ALL cell lines suggested that exosomes with high miR-326 level act as vehicles for reducing cells viability. B-ALL cell line transfection with naked miR-326 mimic confirmed the results, and fluorescence microscopy validated uptake and internalization of exosomes by target cells. The novel introduced features of the exosomal miR-326 address a non-invasive way of diagnosing primary drug resistance in pediatric ALL and advocates a novel therapeutic strategy for this cancer.
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Affiliation(s)
- Neda Saffari
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar jarib Street, Isfahan, 81746-73441, Iran
| | - Soheila Rahgozar
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar jarib Street, Isfahan, 81746-73441, Iran.
| | - Elaheh Faraji
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar jarib Street, Isfahan, 81746-73441, Iran
| | - Fikrettin Sahin
- Department of Genetics and Bioengineering, Yeditepe University, Atasehir, 34755, Istanbul, Turkey
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15
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Huang SH, Hsieh HC, Shieh JM, Su WC, Wang YC. Downregulation of microRNA-326 enhances ZNF322A expression, transcriptional activity and tumorigenic effects in lung cancer. Biofactors 2024; 50:214-227. [PMID: 37647209 DOI: 10.1002/biof.2004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 08/11/2023] [Indexed: 09/01/2023]
Abstract
Zinc finger protein ZNF322A is an oncogenic transcription factor. Overexpression of ZNF322A activates pro-metastasis, cancer stemness, and neo-angiogenesis-related genes to enhance lung cancer progression. However, the upstream regulator of ZNF322A is not well defined. Dysregulation of microRNAs (miRNAs) can mediate cancer cell growth, migration, and invasion to promote tumorigenesis. Here, we uncover the mechanism of miRNA-mediated transcriptional regulation in ZNF322A-driven oncogenic events. ZNF322A harbors several putative miRNA-binding sites in the 3'-untranslated region (UTR). We validated that miR-326 downregulated ZNF322A-3'-UTR luciferase activity and mRNA expression. Furthermore, miR-326 suppressed the expression of ZNF322A-driven cancer-associated genes such as cyclin D1 and alpha-adducin. Reconstitution experiments by ectopic overexpression of ZNF322A abolished miR-326-suppressed cancer cell proliferation and cell migration capacity. Moreover, miR-326 attenuated ZNF322A-induced tumor growth and lung tumor metastasis in vivo. Clinically, the expression of miR-326 negatively correlated with ZNF322A mRNA expression in surgically resected tissues from 120 non-small cell lung cancer (NSCLC) patients. Multivariate Cox regression analysis demonstrated that NSCLC patients with low miR-326/high ZNF322A profile showed poor overall survival. Our results reveal that the deregulated expression of miR-326 leads to hyperactivation of ZNF322A-driven oncogenic signaling. Targeting the miR-326/ZNF322A axis would provide new therapeutic strategies for lung cancer patients.
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Affiliation(s)
- Shih-Hsuan Huang
- Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hung-Chia Hsieh
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Jiunn-Min Shieh
- Division of Chest Medicine, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- The Center of General Education, Chia Nan University of Pharmacy & Science, Tainan, Taiwan
| | - Wou-Chou Su
- Division of Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yi-Ching Wang
- Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
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16
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Pattnaik B, Negi V, Chaudhuri R, Desiraju K, Faizan MI, Akhtar A, Ansari MS, Shakir M, Gheware A, Prakash YS, Guleria R, Ghosh B, Agrawal A, Ahmad T. MiR-326-mediated overexpression of NFIB offsets TGF-β induced epithelial to mesenchymal transition and reverses lung fibrosis. Cell Mol Life Sci 2023; 80:357. [PMID: 37950757 PMCID: PMC11072886 DOI: 10.1007/s00018-023-05005-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 11/13/2023]
Abstract
Idiopathic Pulmonary Fibrosis (IPF) is a progressively fatal and incurable disease characterized by the loss of alveolar structures, increased epithelial-mesenchymal transition (EMT), and aberrant tissue repair. In this study, we investigated the role of Nuclear Factor I-B (NFIB), a transcription factor critical for lung development and maturation, in IPF. Using both human lung tissue samples from patients with IPF, and a mouse model of lung fibrosis induced by bleomycin, we showed that there was a significant reduction of NFIB both in the lungs of patients and mice with IPF. Furthermore, our in vitro experiments using cultured human lung cells demonstrated that the loss of NFIB was associated with the induction of EMT by transforming growth factor beta (TGF-β). Knockdown of NFIB promoted EMT, while overexpression of NFIB suppressed EMT and attenuated the severity of bleomycin-induced lung fibrosis in mice. Mechanistically, we identified post-translational regulation of NFIB by miR-326, a miRNA with anti-fibrotic effects that is diminished in IPF. Specifically, we showed that miR-326 stabilized and increased the expression of NFIB through its 3'UTR target sites for Human antigen R (HuR). Moreover, treatment of mice with either NFIB plasmid or miR-326 reversed airway collagen deposition and fibrosis. In conclusion, our study emphasizes the critical role of NFIB in lung development and maturation, and its reduction in IPF leading to EMT and loss of alveolar structures. Our study highlights the potential of miR-326 as a therapeutic intervention for IPF. The schema shows the role of NFIB in maintaining the normal epithelial cell characteristics in the lungs and how its reduction leads to a shift towards mesenchymal cell-like features and pulmonary fibrosis. A In normal lungs, NFIB is expressed abundantly in the epithelial cells, which helps in maintaining their shape, cell polarity and adhesion molecules. However, when the lungs are exposed to factors that induce pulmonary fibrosis, such as bleomycin, or TGF-β, the epithelial cells undergo epithelial to mesenchymal transition (EMT), which leads to a decrease in NFIB. B The mesenchymal cells that arise from EMT appear as spindle-shaped with loss of cell junctions, increased cell migration, loss of polarity and expression of markers associated with mesenchymal cells/fibroblasts. C We designed a therapeutic approach that involves exogenous administration of NFIB in the form of overexpression plasmid or microRNA-326. This therapeutic approach decreases the mesenchymal cell phenotype and restores the epithelial cell phenotype, thus preventing the development or progression of pulmonary fibrosis.
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Affiliation(s)
- Bijay Pattnaik
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
- Department of Pulmonary, Critical Care & Sleep Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Vinny Negi
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
| | - Rituparna Chaudhuri
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
| | - Koundinya Desiraju
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
| | - Md Imam Faizan
- Multidisciplinary Centre for Advanced Research & Studies, Jamia Millia Islamia, New Delhi, 110025, India
| | - Areej Akhtar
- Multidisciplinary Centre for Advanced Research & Studies, Jamia Millia Islamia, New Delhi, 110025, India
| | - Md Sufyan Ansari
- Multidisciplinary Centre for Advanced Research & Studies, Jamia Millia Islamia, New Delhi, 110025, India
| | - Md Shakir
- Multidisciplinary Centre for Advanced Research & Studies, Jamia Millia Islamia, New Delhi, 110025, India
| | - Atish Gheware
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
| | - Y S Prakash
- Departments of Anesthesiology, Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
| | - Randeep Guleria
- Department of Pulmonary, Critical Care & Sleep Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India
| | - Balaram Ghosh
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India
| | - Anurag Agrawal
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India.
- Trivedi School of Biosciences, Ashoka University, NH 44, Rajiv Gandhi Education City, Sonipat, Haryana, 131029, India.
| | - Tanveer Ahmad
- Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung Disease, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi, 110007, India.
- Multidisciplinary Centre for Advanced Research & Studies, Jamia Millia Islamia, New Delhi, 110025, India.
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17
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Charkiewicz R, Sulewska A, Charkiewicz A, Gyenesei A, Galik B, Ramlau R, Piwkowski C, Stec R, Biecek P, Karabowicz P, Michalska-Falkowska A, Miltyk W, Niklinski J. miRNA-Seq Tissue Diagnostic Signature: A Novel Model for NSCLC Subtyping. Int J Mol Sci 2023; 24:13318. [PMID: 37686123 PMCID: PMC10488146 DOI: 10.3390/ijms241713318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/25/2023] [Accepted: 08/25/2023] [Indexed: 09/10/2023] Open
Abstract
Non-small cell lung cancer (NSCLC) encompasses distinct histopathological subtypes, namely adenocarcinoma (AC) and squamous cell lung carcinoma (SCC), which require precise differentiation for effective treatment strategies. In this study, we present a novel molecular diagnostic model that integrates tissue-specific expression profiles of microRNAs (miRNAs) obtained through next-generation sequencing (NGS) to discriminate between AC and SCC subtypes of NSCLC. This approach offers a more comprehensive and precise molecular characterization compared to conventional methods such as histopathology or immunohistochemistry. Firstly, we identified 31 miRNAs with significant differential expression between AC and SCC cases. Subsequently, we constructed a 17-miRNA signature through rigorous multistep analyses, including LASSO/elastic net regression. The signature includes both upregulated miRNAs (hsa-miR-326, hsa-miR-450a-5p, hsa-miR-1287-5p, hsa-miR-556-5p, hsa-miR-542-3p, hsa-miR-30b-5p, hsa-miR-4728-3p, hsa-miR-450a-1-3p, hsa-miR-375, hsa-miR-147b, hsa-miR-7705, and hsa-miR-653-3p) and downregulated miRNAs (hsa-miR-944, hsa-miR-205-5p, hsa-miR-205-3p, hsa-miR-149-5p, and hsa-miR-6510-3p). To assess the discriminative capability of the 17-miRNA signature, we performed receiver operating characteristic (ROC) curve analysis, which demonstrated an impressive area under the curve (AUC) value of 0.994. Our findings highlight the exceptional diagnostic performance of the miRNA signature as a stratifying biomarker for distinguishing between AC and SCC subtypes in lung cancer. The developed molecular diagnostic model holds promise for providing a more accurate and comprehensive molecular characterization of NSCLC, thereby guiding personalized treatment decisions and improving clinical management and prognosis for patients.
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Affiliation(s)
- Radoslaw Charkiewicz
- Center of Experimental Medicine, Medical University of Bialystok, 15-369 Bialystok, Poland
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland;
| | - Anetta Sulewska
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland;
| | - Alicja Charkiewicz
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; (A.C.); (W.M.)
| | - Attila Gyenesei
- Szentagothai Research Center, Genomic and Bioinformatic Core Facility, H-7624 Pecs, Hungary; (A.G.); (B.G.)
| | - Bence Galik
- Szentagothai Research Center, Genomic and Bioinformatic Core Facility, H-7624 Pecs, Hungary; (A.G.); (B.G.)
| | - Rodryg Ramlau
- Department of Oncology, Poznan University of Medical Sciences, 60-569 Poznan, Poland;
| | - Cezary Piwkowski
- Department of Thoracic Surgery, Poznan University of Medical Sciences, 60-569 Poznan, Poland;
| | - Rafal Stec
- Department of Oncology, Medical University of Warsaw, 02-091 Warsaw, Poland;
| | - Przemyslaw Biecek
- Faculty of Mathematics and Information Science, Warsaw University of Technology, 00-662 Warsaw, Poland;
| | - Piotr Karabowicz
- Biobank, Medical University of Bialystok, 15-269 Bialystok, Poland; (P.K.); (A.M.-F.)
| | | | - Wojciech Miltyk
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; (A.C.); (W.M.)
| | - Jacek Niklinski
- Department of Clinical Molecular Biology, Medical University of Bialystok, 15-269 Bialystok, Poland;
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18
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Ayoufu A, Paierhati P, Qiao L, Zhang N, Abudukeremu M. RUSC1-AS1 promotes the malignant progression of breast cancer depending on the regulation of the miR-326/XRCC5 pathway. Thorac Cancer 2023; 14:2504-2514. [PMID: 37429610 PMCID: PMC10447167 DOI: 10.1111/1759-7714.15035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/24/2023] [Accepted: 06/26/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Many long noncoding RNAs (lncRNAs) are the key regulators for cancer progression, including breast cancer (BC). RUSC1 antisense 1 (RUSC1-AS1) has been found to be highly expressed in BC, but its role and potential molecular mechanism in BC remain to be further elucidated. METHODS Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was utilized to measure RUSC1-AS1, microRNA (miR)-326 and X-ray repair cross-complementing group 5 (XRCC5) expression. Cell proliferation, metastasis, cell cycle, apoptosis and angiogenesis were determined by cell counting kit-8, colony formation, transwell, flow cytometry and tube formation assays. Protein expression was detected by western blot analysis. The targeted relationship between miR-326 and RUSC1-AS1 or XRCC5 was validated using dual-luciferase reporter assay and RIP assay. Xenograft models were constructed to uncover the effect of RUSC1-AS1 on BC tumorigenesis. RESULTS RUSC1-AS1 was upregulated in BC, and its downregulation suppressed BC proliferation, metastasis, cell cycle, angiogenesis, and tumor growth. MiR-326 was confirmed to be sponged by RUSC1-AS1, and its inhibitor reversed the regulation of RUSC1-AS1 silencing on BC progression. XRCC5 could be targeted by miR-326. Overexpression of XRCC5 reversed the inhibitory impacts of miR-326 on BC progression. CONCLUSION RUSC1-AS1 could serve as a sponge of miR-326 to promote BC progression by targeting XRCC5, suggesting that RUSC1-AS1 might be a target for BC treatment.
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Affiliation(s)
- Aisikeer Ayoufu
- Department of Breast Surgery Ward TwoAffiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiChina
| | - Puerkaiti Paierhati
- Department of Breast and Thyroid SurgeryAffiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiChina
| | - Lei Qiao
- Department of Breast and Thyroid SurgeryAffiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiChina
| | - Nan Zhang
- Department of Breast and Thyroid SurgeryAffiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiChina
| | - Muzhapaer Abudukeremu
- Department of Breast and Thyroid SurgeryAffiliated Cancer Hospital of Xinjiang Medical UniversityUrumqiChina
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19
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Abulsoud AI, Elshaer SS, El-Husseiny AA, Fathi D, Abdelmaksoud NM, Abdel Mageed SS, Salman A, Zaki MB, El-Mahdy HA, Ismail A, Elsakka EGE, Abd-Elmawla MA, El-Husseiny HM, Ibrahim WS, Doghish AS. The potential role of miRNAs in the pathogenesis of salivary gland cancer - A Focus on signaling pathways interplay. Pathol Res Pract 2023; 247:154584. [PMID: 37267724 DOI: 10.1016/j.prp.2023.154584] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 05/26/2023] [Accepted: 05/28/2023] [Indexed: 06/04/2023]
Abstract
Salivary gland cancer (SGC) is immensely heterogeneous, both in terms of its physical manifestation and its aggressiveness. Developing a novel diagnostic and prognostic detection method based on the noninvasive profiling of microribonucleic acids (miRs) could be a goal for the clinical management of these specific malignancies, sparing the patients' valuable time. miRs are promising candidates as prognostic biomarkers and therapeutic targets or factors that can advance the therapy of SGC due to their ability to posttranscriptionally regulate the expression of various genes involved in cell proliferation, differentiation, cell cycle, apoptosis, invasion, and angiogenesis. Depending on their biological function, many miRs may contribute to the development of SGC. Therefore, this article serves as an accelerated study guide for SGC and the biogenesis of miRs. Here, we shall list the miRs whose function in SGC pathogenesis has recently been determined with an emphasis on their potential applications as therapeutic targets. We will also offer a synopsis of the current state of knowledge about oncogenic and tumor suppressor miRs in relation to SGC.
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Affiliation(s)
- Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Shereen Saeid Elshaer
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr city, Cairo 11823, Egypt
| | - Ahmed A El-Husseiny
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
| | - Doaa Fathi
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Aya Salman
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Cairo, Egypt
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Menoufia 32897, Egypt
| | - Hesham A El-Mahdy
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Ahmed Ismail
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Elsayed G E Elsakka
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt
| | - Mai A Abd-Elmawla
- Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Hussein M El-Husseiny
- Cooperative Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai Cho, Fuchu-shi, Tokyo 183-8509, Japan; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Elqaliobiya 13736, Egypt
| | - Wael S Ibrahim
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
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20
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Han P, Liu J, Zhao Q, Li H, Zhang T, Li B, Niu X. Circular RNA hsa_circ_0003892 promotes the development of papillary thyroid carcinoma by regulating the miR-326/LASP1 axis. Histol Histopathol 2023; 38:585-595. [PMID: 36394255 DOI: 10.14670/hh-18-546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2023]
Abstract
BACKGROUND Thyroid cancer is the most common malignancy of the endocrine system. Circular RNA (circRNA) is recognized as a key regulator of tumorigenesis in papillary thyroid carcinoma (PTC). Here this work focused on the mechanism of circRNA_0003892 (circ_0003892) in PTC progression. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine circ_0003892, microRNA-326 (miR-326) and LIM and SH3 protein 1 (LASP1) mRNA expression levels in PTC tissues and cell lines. Besides, cell counting kit-8 (CCK-8), EdU and transwell assays were conducted to detect the proliferative, migrative and invasive abilities of PTC cells, respectively. B The targeting relationships between miR-326 and circ_0003892 or LASP1 3'-UTR were verified by dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. RESULTS Circ_0003892 expression was raised in PTC tissues and cells, which was significantly interrelated with larger tumor size and extrathyroidal extension in PTC sufferers. Overexpression of circ_0003892 significantly promoted the malignant biological behaviors of PTC cells. Additionally, miR-326 was a downstream target of circ_0003892, and miR-326 overexpression weakened the promoting effect of circ_0003892 overexpression on the malignant progression of PTC. MiR-326 specifically inhibited LASP1. Circ_0003892 positively regulated LASP1 expression by targeting miR-326. CONCLUSION Circ_0003892 up-regulates LASP1 expression and facilitates PTC progression via competitively binding to miR-326.
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Affiliation(s)
- Peng Han
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Junsong Liu
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Qian Zhao
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Honghui Li
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Ting Zhang
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Baiya Li
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China
| | - Xiaorong Niu
- Department of Otorhinolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
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21
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Wu X, Zhang J, Zhang X, Xiang M, Xu Z, Cao Z. Prognostic value of miR-219-5p in relation to mortality in patients with small cell lung cancer: a retrospective, observational cohort study in China. BMJ Open 2023; 13:e064700. [PMID: 36997257 PMCID: PMC10069522 DOI: 10.1136/bmjopen-2022-064700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/31/2023] Open
Abstract
OBJECTIVES Small cell lung cancer (SCLC) is a lethal human malignancy, and previous studies support the contribution of microRNA to cancer progression. The prognostic value of miR-219-5p in patients with SCLC remains unclear. This study aimed to evaluate the predictive value of miR-219-5p with respect to mortality in patients with SCLC and to incorporate miR-219-5p level into a prediction model and nomogram for mortality. DESIGN Retrospective observational cohort study. SETTING AND PARTICIPANTS Our main cohort included data from 133 patients with SCLC between 1 March 2010 and 1 June 2015 from the Suzhou Xiangcheng People's Hospital. Data from 86 patients with non-SCLC at Sichuan Cancer Hospital and the First Affiliated Hospital of Soochow University were used for external validation. OUTCOME MEASURES Tissue samples were taken during admission and stored, and miR-219-5p levels were measured at a later date. A Cox proportional hazard model was used for survival analyses and for analysing risk factors to create a nomogram for mortality prediction. The accuracy of the model was evaluated by C-index and calibration curve. RESULTS Mortality in patients with a high level of miR-219-5p (≥1.50) (n=67) was 74.6%, while mortality in the low-level group (n=66) was 100.0%. Based on univariate analysis, we included significant factors (p<0.05) in a multivariate regression model: patients with high level of miR-219-5p (HR 0.39, 95% CI 0.26-0.59, p<0.001), immunotherapy (HR 0.44, 95% CI 0.23-0.84, p<0.001) and prognostic nutritional index score >47.9 (HR=0.45, 95% CI 0.24-0.83, p=0.01) remained statistically significant factors for improved overall survival. The nomogram had good accuracy in estimating the risk, with a bootstrap-corrected C-index of 0.691. External validation indicated an area under the curve of 0.749 (0.709-0.788). CONCLUSIONS The miR-219-5p level was associated with a reduced risk of mortality in patients with SCLC. A nomogram incorporating MiR-219-5p level and clinical factors demonstrated good accuracy in estimating the risk of overall mortality. Prospective validation of the prognostic nomogram is needed.
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Affiliation(s)
- Xiangmei Wu
- Endocrinology, Suzhou Xiangcheng People's Hospital, Suzhou, Jiangsu, China
| | - Jigang Zhang
- Traumatology Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Xiaohui Zhang
- Medicine, Respiratory, Emergency and Intensive Care Medicine, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Mengqi Xiang
- Medical Oncology, Medical School of University of Electronic Science and Technology of China, Chengdu, China
| | - Zhihua Xu
- General Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Zhijun Cao
- Urology, Suzhou Ninth People's Hospital, Suzhou, Jiangsu, China
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22
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Circ_0005280 Protects Human Lens Epithelial Cells against H2O2-induced Apoptosis and Oxidative Stress though miR-326/PLCD3 Axis. BIOTECHNOL BIOPROC E 2023. [DOI: 10.1007/s12257-021-0197-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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23
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Ziętara KJ, Lejman J, Wojciechowska K, Lejman M. The Importance of Selected Dysregulated microRNAs in Diagnosis and Prognosis of Childhood B-Cell Precursor Acute Lymphoblastic Leukemia. Cancers (Basel) 2023; 15:428. [PMID: 36672378 PMCID: PMC9856444 DOI: 10.3390/cancers15020428] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 12/30/2022] [Accepted: 01/06/2023] [Indexed: 01/12/2023] Open
Abstract
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a frequent type of childhood hematological malignancy. The disease is classified into several subtypes according to genetic abnormalities. MicroRNAs (miRNAs) are involved in pathological processes (e.g., proliferation, apoptosis, differentiation). A miRNA is a group of short non-coding RNAs with relevant regulatory effects on gene expression achieved by suppression of the translation or degradation of messenger RNA (mRNA). These molecules act as tumor suppressors and/or oncogenes in the pathogenesis of pediatric leukemias. The characteristic features of miRNAs are their stable form and the possibility of secretion to the circulatory system. The role of miRNA in BCP-ALL pathogenesis is still emerging, but several studies have suggested using miRNA expression profiles as biomarkers for diagnosis, prognosis, and response to therapy in leukemia. The dysregulation of some miRNAs involved in childhood acute lymphoid leukemia, such as miR-155, miR-200c, miR-100, miR-181a, miR125b, and miR146a is discussed, showing their possible employment as therapeutic targets. In the current review, the capabilities of miRNAs in non-invasive diagnostics and their prognostic potential as biomarkers are presented.
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Affiliation(s)
- Karolina Joanna Ziętara
- Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland
| | - Jan Lejman
- Independent Public Health Care Facility of The Ministry of Internal Affairs and Administration in Lublin, 20-331 Lublin, Poland
| | - Katarzyna Wojciechowska
- Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-059 Lublin, Poland
| | - Monika Lejman
- Independent Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-059 Lublin, Poland
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24
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Anbazhagan AN, Priyamvada S, Kumar A, Jayawardena D, Borthakur A, Gill RK, Alrefai WA, Dudeja PK, Saksena S. Downregulation of NHE-3 (SLC9A3) expression by MicroRNAs in intestinal epithelial cells. Am J Physiol Cell Physiol 2022; 323:C1720-C1727. [PMID: 36189974 PMCID: PMC9722255 DOI: 10.1152/ajpcell.00294.2022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 09/26/2022] [Accepted: 09/29/2022] [Indexed: 11/22/2022]
Abstract
Na+/H+ exchanger-3 (NHE-3) is the major apical membrane transporter involved in vectorial Na+ absorption in the intestine. Dysregulation of NHE-3 expression and/or function has been implicated in pathophysiology of diarrhea associated with gut inflammation and infections. Therefore, it is critical to understand the mechanisms involved in the regulation of NHE-3 expression. MicroRNAs (miRNAs) are highly conserved small RNAs that can regulate gene expression at the posttranscriptional level. To date, however, very little is known about the regulation of NHE-3 expression by microRNAs. Therefore, current studies were undertaken to examine the potential miRNA candidates that can regulate the expression of NHE-3 in intestinal epithelial cells. In silico analysis, using different algorithms, predicted several miRNAs that target NHE-3. MicroRNAs with highest context and target score, miR-326, miR-744-5p, and miR-330-5p, were selected for the current study. Human NHE-3 gene 3' untranslated region [3'UTR; 160 base pair (bp)] was cloned into pmirGLO vector upstream of luciferase reporter and transiently transfected with mimics of miR-326, miR-744-5p, and miR-330-5p into Caco-2, HT-29, and SK-CO15 cells. Cotransfection of NHE-3 3' UTR with miR-326 and -miR-330-5p mimics resulted in a significant decrease in relative luciferase activity. Transfection of miR-326 and -330-5p mimics into SK-CO15 cells significantly decreased the NHE-3 protein expression, with no change in NHE-3 messenger ribonucleic acid (mRNA) levels. Our findings demonstrate a novel mechanism for posttranscriptional regulation of NHE-3 by miR-326 and -330-5p by translational repression. We speculate that miR-326 and -330-5p dependent pathways may be involved in modulating NHE-3 expression under physiological and pathophysiological conditions.
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Affiliation(s)
- Arivarasu N Anbazhagan
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Shubha Priyamvada
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Anoop Kumar
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
- Jesse Brown VA Medical Center, Chicago, Illinois
| | - Dulari Jayawardena
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Alip Borthakur
- Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia
| | - Ravinder K Gill
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
| | - Waddah A Alrefai
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
- Jesse Brown VA Medical Center, Chicago, Illinois
| | - Pradeep K Dudeja
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
- Jesse Brown VA Medical Center, Chicago, Illinois
| | - Seema Saksena
- Division of Gastroenterology & Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois
- Jesse Brown VA Medical Center, Chicago, Illinois
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25
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Liu X, Zhao X, Yuan Y, Cao Z, Zhu M, Li T, Wu Z. Accurate detection of lung cancer-related microRNA through CRISPR/Cas9-assisted garland rolling circle amplification. J Thorac Dis 2022; 14:4427-4434. [PMID: 36524084 PMCID: PMC9745504 DOI: 10.21037/jtd-22-1405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Accepted: 11/03/2022] [Indexed: 02/19/2024]
Abstract
BACKGROUND MicroRNA (miRNA) is reported to be closely related to a variety of pathophysiological processes for carcinoma and considered a potential biomarker for the diagnosis of lung cancer with brain metastasis. However, developing an accurate and sensitive miRNA detection method has proven to be a challenge. The aim of the present study was to integrate the advantages of rolling circle amplification (RCA), clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nucleases 9 (Cas9), and catalytic hairpin assembly (CHA) technologies to develop an miRNA detection method. METHODS In the present study, we developed a novel approach for the sensitive and accurate detection of miRNA through integrating garland RCA and CRISPR/Cas9-assisted signal generation. In this method, target miRNA cyclized dumbbell padlock and triggered the RCA process to form long single-stranded DNA products with a repeated hairpin structure. Double-stranded DNA sequences (dsDNA) were formed with the addition of complementary sequences. With the assistance of the Cas9 enzyme for specific recognition and cleavage of formed dsDNA, RCA products were disassembled into hairpin probes. The generated hairpin probe could be unfolded by target miRNA to initiate the CHA process for signal generation. RESULTS Through integration of the RCA and CHA processes, the method demonstrated favorable detection performance. The correlation equation between the signal and concentration of target miRNA was determined to be Y=312.3 × lgC + 2108, with a high correlation coefficient of 0.9786. The approach also exhibited high selectivity to the mismatched miRNAs. CONCLUSIONS Our method could be used in the screening, diagnosis, and prognosis of multiple diseases without complicated thermal cycling instrumentation.
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Affiliation(s)
- Xiaoya Liu
- Department of Oncology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xianxian Zhao
- Department of Clinical Laboratory, Southwest Hospital, Army Medical University, Chongqing, China
| | - Ye Yuan
- Department of Clinical Laboratory, Southwest Hospital, Army Medical University, Chongqing, China
| | - Zhenrui Cao
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingxue Zhu
- Department of Pharmacy, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tingting Li
- Breast Disease Center, Southwest Hospital, Army Medical University, Chongqing, China
| | - Zhongjun Wu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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26
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Yang L, Chen Y. Circ_0008717 Sponges miR-326 to Elevate GATA6 Expression to Promote Breast Cancer Tumorigenicity. Biochem Genet 2022; 61:578-596. [PMID: 36001185 DOI: 10.1007/s10528-022-10270-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 08/05/2022] [Indexed: 12/09/2022]
Abstract
Circular RNAs (circRNAs) have been reported to paly roles in the progression and management of breast cancers (BC). This work aimed to detect the role and mechanism of circ_0008717 in BC tumorigenesis. Expression levels of genes and proteins were evaluated by quantitative real-time polymerase chain reaction and western blot. In vitro assays were conducted using cell counting kit-8, colony formation, transwell, tube formation, and flow cytometry assays, respectively. The interaction between miR-326 and circ_0008717 or GATA6 (GATA Binding Protein six) was confirmed by bioinformatics analysis, and dual-luciferase reporter assay and RNA immunoprecipitation assay. The murine xenograft models were established to perform in vivo assay. Circ_0008717 and GATA6 were highly expressed, while miR-326 was lowly expressed in BC tissues and cells. Functionally, knockdown of circ_0008717 not only suppressed breast cancer cell proliferation, angiogenesis, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro, but also hindered tumor growth and EMT process in vivo. Mechanistically, Circ_0008717 directly bound to miR-326, which targeted GATA6. Rescue experiments showed that miR-326 reversed the anticancer action of circ_0008717 knockdown on BC cells. Moreover, miR-326 restoration repressed BC cell growth and metastasis, which were attenuated by GATA6 overexpression. In addition, we also observed that circ_0008717 could regulate GATA6 expression by sponging miR-326. Circ_0008717 promoted breast cancer growth and metastasis through miR-326/GATA6 axis, revealing a potential therapeutic target for breast cancer treatment.
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Affiliation(s)
- Ling Yang
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.,Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, No. 20, Section 3, Renmin South Road, Chengdu, 610041, China
| | - Yuxin Chen
- Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, 610041, China. .,Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, No. 20, Section 3, Renmin South Road, Chengdu, 610041, China.
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Wu H, Du J, Li C, Li H, Guo H, Li Z. Kaempferol Can Reverse the 5-Fu Resistance of Colorectal Cancer Cells by Inhibiting PKM2-Mediated Glycolysis. Int J Mol Sci 2022; 23:3544. [PMID: 35408903 PMCID: PMC8998549 DOI: 10.3390/ijms23073544] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/21/2022] [Accepted: 03/22/2022] [Indexed: 02/04/2023] Open
Abstract
Resistance to 5-Fluorouracil (5-Fu) chemotherapy is the main cause of treatment failure in the cure of colon cancer. Therefore, there is an urgent need to explore a safe and effective multidrug resistance reversal agent for colorectal cancer, which would be of great significance for improving clinical efficacy. The dietary flavonoid kaempferol plays a key role in the progression of colorectal cancer and 5-Fu resistance. However, the molecular mechanism of kaempferol in reversing 5-Fu resistance in human colorectal cancer cells is still unclear. We found that kaempferol could reverse the drug resistance of HCT8-R cells to 5-Fu, suggesting that kaempferol alone or in combination with 5-Fu has the potential to treat colorectal cancer. It is well known that aerobic glycolysis is related to tumor growth and chemotherapy resistance. Indeed, kaempferol treatment significantly reduced glucose uptake and lactic acid production in drug-resistant colorectal cancer cells. In terms of mechanism, kaempferol promotes the expression of microRNA-326 (miR-326) in colon cancer cells, and miR-326 could inhibit the process of glycolysis by directly targeting pyruvate kinase M2 isoform (PKM2) 3'-UTR (untranslated region) to inhibit the expression of PKM2 or indirectly block the alternative splicing factors of PKM mRNA, and then reverse the resistance of colorectal cancer cells to 5-Fu. Taken together, our data suggest that kaempferol may play an important role in overcoming resistance to 5-Fu therapy by regulating the miR-326-hnRNPA1/A2/PTBP1-PKM2 axis.
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Affiliation(s)
- Haili Wu
- College of Life Science, Shanxi University, Taiyuan 030006, China; (H.W.); (J.D.); (C.L.); (H.L.)
| | - Jin’e Du
- College of Life Science, Shanxi University, Taiyuan 030006, China; (H.W.); (J.D.); (C.L.); (H.L.)
| | - Chenglu Li
- College of Life Science, Shanxi University, Taiyuan 030006, China; (H.W.); (J.D.); (C.L.); (H.L.)
| | - Hanqing Li
- College of Life Science, Shanxi University, Taiyuan 030006, China; (H.W.); (J.D.); (C.L.); (H.L.)
| | - Huiqin Guo
- The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China;
| | - Zhuoyu Li
- The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China;
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Zhang K, Fang T, Zhao D, Cen F, Yan X, Jin X. Circular RNA Circ_0008043 promotes the proliferation and metastasis of hepatocellular carcinoma cells by regulating the microRNA (miR)-326/RAB21 axis. Bioengineered 2022; 13:6600-6614. [PMID: 35220907 PMCID: PMC8973620 DOI: 10.1080/21655979.2022.2044260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Circular RNAs (circRNAs) are non-coding RNAs with covalently closed structures that modulate the progression of hepatocellular carcinoma (HCC). Here, we explored whether circ_0008043 regulated the biological function of HCC cells. Quantitative real-time polymerase chain reaction (qPCR) was used to detect circ_0008043, microRNA (miR)-326, and RAB21 levels. Expression of E-cadherin, N-cadherin, and vimentin was assessed using qPCR. Cell proliferation, migration, and invasion were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, and transwell assays. Xenograft tumors were used to evaluate cell growth in vivo. The interaction between miR-326 and circ_0008043 or RAB21 was assessed using dual-luciferase reporter analysis and RNA pull-down analysis. The data illustrated that circ_0008043 and RAB21 were highly expressed, while miR-326 was expressed at less levels in HCC tissues and cells. Interfering with circ_0008043 suppressed cellular proliferation, migration, invasion, and cell growth. Circ_0008043 was confirmed to be an miR-326 sponge that targets RAB21. Rescue experiments showed that inhibiting miR-326 abrogated the effect induced by knockdown of circ_0008043, and overexpressed RAB21 abolished the effect induced by miR-326 overexpression. In summary, silencing of circ_0008043 impeded HCC progression by regulating the miR-326/RAB21 axis. These data suggest that circ_0008043 may have clinical value in the treatment of HCC.
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Affiliation(s)
- Kangjun Zhang
- Hepatic Surgery Department, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China
| | - Taishi Fang
- Hepatic Surgery Department, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China
| | - Dong Zhao
- Hepatic Surgery Department, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China
| | - Fulan Cen
- Department of Intensive Care Unit, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China
| | - Xu Yan
- Hepatic Surgery Department, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China
| | - Xin Jin
- Hepatic Surgery Department, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, China
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hsa_circ_0139402 Promotes Bladder Cancer Progression by Regulating hsa-miR-326/PAX8 Signaling. DISEASE MARKERS 2022; 2022:9899548. [PMID: 35154515 PMCID: PMC8824756 DOI: 10.1155/2022/9899548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 01/04/2022] [Accepted: 01/06/2022] [Indexed: 12/20/2022]
Abstract
Background Bladder cancer (BC) is a malignant and common malignant tumors. However, the prognosis of most patients with bladder cancer is still poor, and it is particularly important to identify early tumor diagnostic and treatment targets. Materials and Methods High-throughput sequencing was used to evaluate the expression level of circRNA in bladder cancer tissue. MTT assay, wound healing assay, and transwell assay were used to detect the cancer cells' proliferation, migration, and invasion affected by hsa_circ_0139402. The possible miRNA targets of hsa_circ_0139402 and downstream genes were detected by bioinformatics methods and dual-luciferase reporting experiment. FISH was used to observe their interaction. Results High-throughput sequencing result showed that the expression of hsa_circ_0139402 was highest in BC tissues and increased in metastatic tissues compared to that of nonmetastatic tissues. MTT assay, wound healing assay, and transwell assay revealed that sh-hsa_circ_0139402 could suppress BC cells' proliferation, invasion, and migration. Bioinformatics analysis, dual-luciferase reporter, and RIP assay showed that hsa_circ_0139402 can bind to hsa-miR-326, and PAX8 is a direct target of hsa-miR-326 in BC cell. Further, cytological studies found that hsa_circ_0139402 enhances BC cells' proliferation, migration, and invasion by targeting PAX8 via hsa-miR-326. Conclusion hsa_circ_0139402 plays a oncogene in BC and that can effectively promote cell proliferation, migration, invasion, and EMT by targeting Paired Box Protein Pax-8 (PAX8) via hsa-miR-326 and provides a potential therapeutic target for BC patients.
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Gao Y, Zhang Q, Sun J, Liang Y, Zhang M, Zhao M, Zhang K, Dong C, Ma Q, Liu W, Li W, Chen Y, Han L, Jin F. Extracellular vesicles derived from PM2.5‐exposed alveolar epithelial cells mediate endothelial adhesion and atherosclerosis in ApoE
−/−
mice. FASEB J 2022; 36:e22161. [PMID: 35061300 DOI: 10.1096/fj.202100927rr] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 12/26/2021] [Accepted: 12/29/2021] [Indexed: 12/23/2022]
Affiliation(s)
- Yongheng Gao
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Qian Zhang
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Jinbo Sun
- Department of Urology General Hospital of the Central Theater Command Wuhan China
| | - Yuan Liang
- Department of Geriatrics 920th Hospital of Joint Logistics Support Force Kunming China
| | - Minlong Zhang
- Department of Respiration The 309th Hospital of the Chinese People's Liberation Army Beijing China
| | - Mingxuan Zhao
- Research Center of Clinical Pharmacology the First Affiliated Hospital of Yunnan University of Chinese Medicine Kunming China
| | - Kailiang Zhang
- Department of Orthopedics Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Chuan Dong
- Department of Orthopedics Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Qiong Ma
- Department of Orthopedics Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Wei Liu
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Wangping Li
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Yanwei Chen
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Luyao Han
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
| | - Faguang Jin
- Department of Respiration Tangdu Hospital Fourth Military Medical University Xi'an China
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Li X, Su S, Ye D, Yu Z, Lu W, Liu L. Hsa_circ_0020850 promotes the malignant behaviors of lung adenocarcinoma by regulating miR-326/BECN1 axis. World J Surg Oncol 2022; 20:13. [PMID: 35012553 PMCID: PMC8750879 DOI: 10.1186/s12957-021-02480-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 12/17/2021] [Indexed: 11/10/2022] Open
Abstract
Background Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown. Methods The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo. Results We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1. Conclusion Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02480-3.
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Affiliation(s)
- Xiaoju Li
- Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China
| | - Shengtian Su
- Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China
| | - Dan Ye
- Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China
| | - Zhigao Yu
- Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China
| | - Wenjing Lu
- Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China
| | - Liang Liu
- Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China.
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Zhang Q, Huang XM, Liao JX, Dong YK, Zhu JL, He CC, Huang J, Tang YW, Wu D, Tian JY. LncRNA HOTAIR Promotes Neuronal Damage Through Facilitating NLRP3 Mediated-Pyroptosis Activation in Parkinson's Disease via Regulation of miR-326/ELAVL1 Axis. Cell Mol Neurobiol 2021; 41:1773-1786. [PMID: 32968928 PMCID: PMC11444004 DOI: 10.1007/s10571-020-00946-8] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/14/2020] [Indexed: 12/30/2022]
Abstract
Parkinson's disease (PD) seriously threatens human's health. Researches have shown a close correlation between long non-coding RNAs (lncRNAs) and PD. However, the biological function of lncRNA homeobox transcript antisense RNA (HOTAIR) in PD remains largely unknown. In this study, we established PD models in vivo and in vitro by using 1-methyl-4-phenyl-2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+) to assess the role of HOTAIR in pyroptotic cell death and neuronal damage. RNA immunoprecipitation (RIP) and dual luciferase reporter assay were used to verify the interaction between miR-326 and HOTAIR or ELAV like RNA binding protein 1 (ELAVL1). LncRNA HOTAIR was upregulated in PD mice and MPP+ induced SH-SY5Y cells. Additionally, knockdown of HOTAIR notably attenuated the symptom of PD in vivo. Downregulation of HOTAIR could obviously promoted cell viability and suppressed NLR family pyrin domain containing 3 (NLRP3) mediated pyroptotic cell death of SH-SY5Y cells in the presence of MPP+. Further, lncRNA HOTAIR positively regulated ELAVL1 expression by targeting miR-326, and downregulation of HOTAIR or ELAVL1 notably suppressed promotive effects of miR-326 inhibitor on MPP+ induced pyroptosis via activation of NLRP3 inflammasome. Collectively, HOTAIR silencing significantly inhibits neuronal damage through repressing NLRP3 mediated pyroptosis activation via regulation of miR-326/ELAVL1 axis in PD, which may contribute to a better understanding of PD pathogenesis and provide new treatment strategies for this disease.
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Affiliation(s)
- Qian Zhang
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Xiao-Mo Huang
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Jian-Xiong Liao
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Yu-Kang Dong
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Jiang-Lan Zhu
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Cun-Cun He
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Jia Huang
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Yao-Wei Tang
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Dan Wu
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China
| | - Jin-Yong Tian
- Department of Emergency, Guizhou Province, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, P.R. China.
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Saliani M, Mirzaiebadizi A, Mosaddeghzadeh N, Ahmadian MR. RHO GTPase-Related Long Noncoding RNAs in Human Cancers. Cancers (Basel) 2021; 13:5386. [PMID: 34771549 PMCID: PMC8582479 DOI: 10.3390/cancers13215386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/21/2021] [Accepted: 10/22/2021] [Indexed: 12/27/2022] Open
Abstract
RHO GTPases are critical signal transducers that regulate cell adhesion, polarity, and migration through multiple signaling pathways. While all these cellular processes are crucial for the maintenance of normal cell homeostasis, disturbances in RHO GTPase-associated signaling pathways contribute to different human diseases, including many malignancies. Several members of the RHO GTPase family are frequently upregulated in human tumors. Abnormal gene regulation confirms the pivotal role of lncRNAs as critical gene regulators, and thus, they could potentially act as oncogenes or tumor suppressors. lncRNAs most likely act as sponges for miRNAs, which are known to be dysregulated in various cancers. In this regard, the significant role of miRNAs targeting RHO GTPases supports the view that the aberrant expression of lncRNAs may reciprocally change the intensity of RHO GTPase-associated signaling pathways. In this review article, we summarize recent advances in lncRNA research, with a specific focus on their sponge effects on RHO GTPase-targeting miRNAs to crucially mediate gene expression in different cancer cell types and tissues. We will focus in particular on five members of the RHO GTPase family, including RHOA, RHOB, RHOC, RAC1, and CDC42, to illustrate the role of lncRNAs in cancer progression. A deeper understanding of the widespread dysregulation of lncRNAs is of fundamental importance for confirmation of their contribution to RHO GTPase-dependent carcinogenesis.
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Affiliation(s)
- Mahsa Saliani
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
- Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad 9177948974, Iran
| | - Amin Mirzaiebadizi
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
| | - Niloufar Mosaddeghzadeh
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
| | - Mohammad Reza Ahmadian
- Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University, 40225 Düsseldorf, Germany
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Abstract
The proliferation, metastasis and therapy response of tumour cells are tightly regulated by interaction among various signalling networks. The microRNAs (miRNAs) can bind to 3'-UTR of mRNA and down-regulate expression of target gene. The miRNAs target various molecular pathways in regulating biological events such as apoptosis, differentiation, angiogenesis and migration. The aberrant expression of miRNAs occurs in cancers and they have both tumour-suppressor and tumour-promoting functions. On the contrary, SOX proteins are capable of binding to DNA and regulating gene expression. SOX2 is a well-known member of SOX family that its overexpression in different cancers to ensure progression and stemness. The present review focuses on modulatory impact of miRNAs on SOX2 in affecting growth, migration and therapy response of cancers. The lncRNAs and circRNAs can function as upstream mediators of miRNA/SOX2 axis in cancers. In addition, NF-κB, TNF-α and SOX17 are among other molecular pathways regulating miRNA/SOX2 axis in cancer. Noteworthy, anti-cancer compounds including bufalin and ovatodiolide are suggested to regulate miRNA/SOX2 axis in cancers. The translation of current findings to clinical course can pave the way to effective treatment of cancer patients and improve their prognosis.
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Lin LN, Zhang QM, Ge YY, Luo B, Xie XX. A Review of miR-326 and Female Related Diseases. Acta Histochem Cytochem 2021; 54:79-86. [PMID: 34276101 PMCID: PMC8275862 DOI: 10.1267/ahc.20-00027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 03/07/2021] [Indexed: 12/16/2022] Open
Abstract
MicroRNA (miRNA), a non-coding single-stranded RNA molecule with 20–23 nucleotides encoded by endogenous genes, plays an essential role in maintaining normal cell function and regulating cell proliferation, differentiation, apoptosis, autophagy, and cell metabolism. The imbalance between miRNA and genes can cause a series of diseases, including malignancies. miRNA-326 (miR-326) is extensively known for its core regulation of various biological processes. This review presents an overview of the highlights of miR-326 in female-related diseases. To understand the impact of miR-326 on female disorders, we search all published studies about miR-326 having a high incidence in female conditions, including cervical cancer, endometrial cancer, breast cancer, intrauterine adhesion, and multiple autoimmune diseases. We aim to learn about the mutual regulation mechanism between miR-326 and related genes and signaling pathways, as well as to elaborate on the value of miR-326 as a potential biomarker and therapeutic target of female diseases. Our results provide reliable evidence and new strategies for treating female tumors and autoimmune diseases.
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Affiliation(s)
- Li-na Lin
- Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University
| | - Qing-mei Zhang
- Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University
- Key Laboratory Research of Preclinical Medicine of Guangxi Colleges and Universities, Guangxi Medical University
| | - Ying-ying Ge
- Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University
- Key Laboratory Research of Preclinical Medicine of Guangxi Colleges and Universities, Guangxi Medical University
| | - Bin Luo
- Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University
- Key Laboratory Research of Preclinical Medicine of Guangxi Colleges and Universities, Guangxi Medical University
| | - Xiao-xun Xie
- Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University
- Key Laboratory Research of Preclinical Medicine of Guangxi Colleges and Universities, Guangxi Medical University
- Key Laboratory of Early Prevention and Treatment of Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education
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MicroRNA-326 attenuates immune escape and prevents metastasis in lung adenocarcinoma by targeting PD-L1 and B7-H3. Cell Death Discov 2021; 7:145. [PMID: 34131111 PMCID: PMC8206349 DOI: 10.1038/s41420-021-00527-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 04/23/2021] [Accepted: 05/23/2021] [Indexed: 12/11/2022] Open
Abstract
Tumor-infiltrating T cells are highly expressive of inhibitory receptor/immune checkpoint molecules that bind to ligand expressed by tumor cells and antigen-presenting cells, and eventually lead to T cell dysfunction. It is a hot topic to restore T cell function by targeting immune checkpoint. In recent years, immunotherapy of blocking immune checkpoint and its receptor, such as PD-L1/PD-1 targeted therapy, has made effective progress, which brings hope for patients with advanced malignant tumor. However, only a few patients benefit from directly targeting these checkpoints or their receptors by small compounds or antibodies. Since the complexity of the regulation of immune checkpoints in tumor cells, further research is needed to identify the novel endogenous regulators of immune checkpoints which can help for developing effective drug target to improve the effect of immunotherapy. Here, we verified that microRNA-326 (miR-326) repressed the gene expression of immune checkpoint molecules PD-L1 and B7-H3 in lung adenocarcinoma (LUAD). We detected that the expression of miR-326 in LUAD tissue was negatively correlated with PD-L1/B7-H3. The repression of PD-L1 and B7-H3 expression through miR-326 overexpression leads to the modification the cytokine profile of CD8+ T cells and decreased migration capability of tumor cells. Meanwhile, the downregulation of miR-326 promoted tumor cell migration. Moreover, blocking PD-L1 and B7-H3 attenuated the tumor-promoting effect induced by miR-326 inhibitor. In tumor-bearing mice, the infiltration of CD8+ T cells was significantly increased and the expression of TNF-α, and IFN-γ was significantly enhanced which contributed to tumor progression after miR-326 overexpression. Collectively, miR-326 restrained tumor progression by downregulating PD-L1 and B7-H3 expression and increasing T cell cytotoxic function in LUAD. Our findings revealed a novel perspective on the complex regulation of immune checkpoint molecules. A new strategy of using miR-326 in tumor immunotherapy is proposed.
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Qi L, Sun B, Yang B, Lu S. circHIPK3 (hsa_circ_0000284) Promotes Proliferation, Migration and Invasion of Breast Cancer Cells via miR-326. Onco Targets Ther 2021; 14:3671-3685. [PMID: 34135597 PMCID: PMC8200520 DOI: 10.2147/ott.s299190] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Accepted: 03/18/2021] [Indexed: 12/31/2022] Open
Abstract
Purpose circHIPK3 has carcinogenic or anti-tumor effects on different cancers. However, there is no relevant research showing whether circHIPK3 was involved in breast cancer (BCa). In this research, the aim was to analyze the function and possible molecular mechanism of circHIPK3 in BCa. Methods The expression of circHIPK3 in human BCa tissues and cells was detected by real-time quantitative PCR (RT-qPCR). CircInteractome and dual-luciferase assays were performed to detect circRNA-miRNA targeting relationship. Ribonuclease R treatment, RT-qPCR, Western blot and immunohistochemistry were performed to determine the stability, expressions, abundance of target genes. Loss-of-function or gain-of-function experiments were used to analyze the effects of circHIPK3 and miR-326 on BCa in vivo and in vitro. In vitro, MCF7 and BT20 cells were transfected with circHIPK3 or sicircHIPK3 or miR-326 mimic; in vivo, female BALB/c mice were subcutaneously injected with MCF7 cells (transfected with CirchipK3 or miR-326 mimic) to establish xenograft models. Results The circular structure of circHIPK3 was abundantly expressed in the cytoplasm and was up-regulated in BCa. Silenced circHIPK3 suppressed malignant phenotype of BCa cells. MiR-326 interacted with circHIPK3 and the two were negatively correlated. Overexpressed circHIPK3 promoted cell viability, proliferation, migration and invasion, but inhibited apoptosis. Moreover, overexpressed circHIPK3 promoted the expressions of EMT-related genes and antiapoptotic genes, but inhibited proapoptotic gene expressions. Overexpressed circHIPK3 promoted tumor growth and Ki-67 levels, inhibited apoptosis in vivo. The above mentioned effects of circHIPK3 were reversed by miR-326 in vitro or in vivo. Conclusion circHIPK3 promoted proliferation, migration and invasion of BCa cells through regulating miR-326.
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Affiliation(s)
- Liqiang Qi
- Department of Breast Surgical Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Bo Sun
- The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Beibei Yang
- The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
| | - Su Lu
- The 2nd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, People's Republic of China
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Zhang J, Zhang Z. Mechanisms of circular RNA circ_0066147 on pancreatic cancer progression. Open Life Sci 2021; 16:495-510. [PMID: 34056113 PMCID: PMC8142380 DOI: 10.1515/biol-2021-0047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 03/09/2021] [Accepted: 03/11/2021] [Indexed: 12/09/2022] Open
Abstract
Background The purpose of the study was to explore the precise parts of circ_0066147 (circular RNA [circRNA] scm-like with four mbt domains 1, circSFMBT1) in pancreatic cancer (PC) progression. Methods Ribonuclease R assay was used to confirm the stability of circ_0066147. circ_0066147, miR-326 and E2F transcription factor 2 (E2F2) expression levels was detected by quantitative reverse-transcription polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration and invasion abilities were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, flow cytometry, wound-healing and transwell assays, respectively. Targeted relationships among circ_0066147, miR-326 and E2F2 were verified by the dual-luciferase reporter or RNA pull-down assay. Results circ_0066147 expression was upregulated in PC tissues and cells. circ_0066147 knockdown inhibited PC cell proliferation, migration, invasion and enhanced apoptosis in vitro, as well as weakened tumor growth in vivo. Mechanistically, circ_0066147 directly targeted miR-326 and circ_0066147 modulated E2F2 expression by miR-326. miR-326 mediated the regulation of circ_0066147 in PC cell behaviors in vitro. Furthermore, E2F2 was a functional target of miR-326 in modulating PC cell behaviors in vitro. Conclusion circ_0066147 regulated PC malignant progression in part depending on the miR-326/E2F2 axis, illuminating circ_0066147 was a potential prognostic marker and therapeutic target for PC management.
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Affiliation(s)
- Jie Zhang
- Second Department of Tumor Intervention, The Second People’s Hospital of Wuhu, No. 259 Jiuhua Middle Road, Jinghu District 241000, Wuhu, Anhui, China
| | - Zhang Zhang
- Second Department of Tumor Intervention, The Second People’s Hospital of Wuhu, No. 259 Jiuhua Middle Road, Jinghu District 241000, Wuhu, Anhui, China
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Zhao X, Tian Z, Liu L. circATP2B1 Promotes Aerobic Glycolysis in Gastric Cancer Cells Through Regulation of the miR-326 Gene Cluster. Front Oncol 2021; 11:628624. [PMID: 33996547 PMCID: PMC8120303 DOI: 10.3389/fonc.2021.628624] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/09/2021] [Indexed: 12/30/2022] Open
Abstract
The discovery of circular RNA (circRNA) enormously complimented the repertoire of traditional gene expression theory. As a type of endogenous noncoding RNA, circRNA participates in the occurrence of many kinds of tumors in addition to regulating their development. The Warburg effect (aerobic glycolysis is taken with priority for cancer cells instead of oxidative phosphorylation) is one of the most important factors involved in the excessive proliferation of gastric cancer cells. Our data showed that circRNA circATP2B1 (also called hsa_circ_000826) was overexpressed in gastric cancer tissues instead of linear ATP2B1 mRNA, and it promoted aerobic glycolysis in gastric cancer cells. Bioinformatic Gene Ontology analysis showed that the potential downstream targets of circATP2B1 include the microRNA miR-326 gene cluster (miR-326-3p/miR-330-5p), which is functionally focused on cell growth and metabolic processes. The expressions of miR-326-3p/miR-330-5p were downregulated in gastric cancer, and circATP2B1 functionally targeted miR-326-3p/miR-330-5p in an RNA-induced silencing complex (RISC) dependent manner. Dual-luciferase reporter assays demonstrated that pyruvate kinase M2 (PKM2) was one of the targets of miR-326-3p/miR-330-5p. As a rate-limiting enzyme in the aerobic glycolytic pathway, PKM2 accelerated gastric cancer cells' glucose uptake and increased cell viability. Taken together, circATP2B1 captured miR-326-3p/miR-330-5p and decreased the suppression of PKM2 by miR-326-3p/miR-330-5p, thus aiding the aerobic glycolysis and proliferation of gastric cancer cells. This study identified a novel molecular pathway in gastric cancer that may provide more targets for reversing cancer metabolic reprogramming, as well as a potential strategy for targeted therapy of gastric cancer.
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Affiliation(s)
- Xihe Zhao
- Department of Clinical Oncology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhong Tian
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Lei Liu
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China
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Chen C, Zong Y, Tang J, Ke R, Lv L, Wu M, Lu J. miR-369-3p serves as prognostic factor and regulates cancer progression of hepatocellular carcinoma. Per Med 2021; 18:375-388. [PMID: 33792408 DOI: 10.2217/pme-2020-0012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Background: The aim of this study was to investigate the role of miR-369-3p in hepatocellular carcinoma (HCC). Materials & methods: The expression levels of miR-369-3p were detected using the quantitative real-time reverse transcription-PCR analysis. The cell counting kit-8 and transwell assays were used to explore the effects of miR-369-3p on cell proliferation, migration and invasion of HCC cells. Results: The miR-369-3p expression was downregulated in HCC tissues and cell lines, in comparison to the normal controls, respectively. In vitro, overexpression of miR-369-3p in Hep 3B and Huh7 cells inhibited cell proliferation, migration and invasion. SOX4 was a direct target of miR-369-3p. Conclusion: Our results suggested that miR-369-3p may be a tumor suppressor in HCC by targeting SOX4.
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Affiliation(s)
- Can Chen
- The Graduate School of Fujian Medical University, Fuzhou, Fujian, 350108, PR China.,Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, 200438, PR China
| | - Yi Zong
- The Graduate School of Fujian Medical University, Fuzhou, Fujian, 350108, PR China.,The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, 200438, PR China
| | - Jiaojiao Tang
- Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, 200438, PR China
| | - Ruisheng Ke
- Department of General Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, 361003, PR China
| | - Lizhi Lv
- Department of Hepatobiliary Surgery, 900 Hospital of the Joint Logistics Team, Fuzhou, 350025, PR China
| | - Mengchao Wu
- Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, 200438, PR China
| | - Junhua Lu
- The 5th Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, 200438, PR China
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Zhang Q, Cheng F, Zhang Z, Wang B, Zhang X. Propofol suppresses non-small cell lung cancer tumorigenesis by regulation of circ-RHOT1/miR-326/FOXM1 axis. Life Sci 2021:119042. [PMID: 33515563 DOI: 10.1016/j.lfs.2021.119042] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 12/22/2020] [Accepted: 01/03/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Lung cancer is a common malignant tumor around the world. Propofol has been found to play an anti-tumor role. Therefore, the purpose of this study is to clarify the role and underlying molecular mechanisms of Propofol in non-small cell lung cancer (NSCLC). METHODS The real-time quantitative polymerase chain reaction (RT-qPCR) assay was conducted to measure the expression levels of circular_RHOT1 (circ-RHOT1), microRNA (miR)-326, and Forkhead Box M1 (FOXM1) in tissues and cells. The proliferation of cell was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and colony forming assays. The flow cytometry assay was used to evaluate cell apoptosis. The migration and invasion of NSCLC cells were determined by transwell assay. The protein expression level of FOXM1 was quantified by western blot assay. The association between miR-326 and circ-RHOT1 or FOXM1 was confirmed by dual-luciferase reporter assay. RESULTS Circ-RHOT1 was increased in NSCLC tissues and cells. Importantly, treatment with Propofol inhibited circ-RHOT1 expression in NSCLC cells. Propofol dose-dependently inhibited proliferation, migration and invasion while induced apoptosis of NSCLC cells, which was abolished by circ-RHOT1 overexpression, FOXM1 overexpression, or miR-326 silencing. MiR-326, interacted with FOXM1, was a target of circ-RHOT1 in NSCLC cells, which was confirmed by dual-luciferase reporter assay. Circ-RHOT1 regulated FOXM1 expression by sponging miR-326 in NSCLC cells. In addition, inhibition of circ-RHOT1 in combined with Propofol impeded tumorigenesis in vivo. CONCLUSION Propofol repressed proliferation, migration and invasion while induced apoptosis of NSCLC cells at least in part by regulation of circ-RHOT1/miR-326/FOXM1 axis in NSCLC cells.
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Affiliation(s)
- Qian Zhang
- Department of Anesthesiology, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang 222000, Jiangsu, China.
| | - Fang Cheng
- Department of Anesthesiology, Lianyungang Oriental Hospital, Lianyungang, Jiangsu, China
| | - Zhaojian Zhang
- Department of Anesthesiology, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang 222000, Jiangsu, China
| | - Bing Wang
- Department of Anesthesiology, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang 222000, Jiangsu, China
| | - Xiaobao Zhang
- Department of Anesthesiology, The First People's Hospital of Lianyungang, 182 Tongguan Road, Lianyungang 222000, Jiangsu, China
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Tu J, Wu F, Chen L, Zheng L, Yang Y, Ying X, Song J, Chen C, Hu X, Zhao Z, Ji J. Long Non-Coding RNA PCAT6 Induces M2 Polarization of Macrophages in Cholangiocarcinoma via Modulating miR-326 and RhoA-ROCK Signaling Pathway. Front Oncol 2021; 10:605877. [PMID: 33552977 PMCID: PMC7859434 DOI: 10.3389/fonc.2020.605877] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Accepted: 11/30/2020] [Indexed: 12/20/2022] Open
Abstract
LncRNAs can act crucial roles in multiple tumors including cholangiocarcinoma (CCA). M2 polarization of macrophages is crucial for their biological roles in immunologic tolerance, which is able to induce tumorigenesis. Given that increasing evidence have suggested that lncRNAs could participate in modulating immune cell differentiation and function. Our current study was aimed to identify the underlying mechanism of lncRNA prostate cancer-associated transcript 6 (PCAT6) in CCA progression via regulating M2 macrophage polarization. PCAT6 has been reported as an oncogene in many cancers. In our work, we observed increased expression of PCAT6 in CCA patients. PCAT6 expression in various types of immune cells derived from CCA patients was tested by quantitative real-time PCR (qRT-PCR). It was revealed that PCAT6 was highly expressed in macrophages, which indicated that PCAT6 might regulate the function of macrophages to promote CCA progression. Then, via establishing CCA xenograft mouse model, we found loss of PCAT6 obviously triggered the immune response and reduced the in vivo tumor growth. In addition, overexpression of PCAT6 led to the M2 polarization of THP-1-differentiated macrophages. Moreover, miR-326 was predicted and proved as a target for PCAT6. In addition, down-regulation of PCAT6 repressed M2 polarization of macrophages, which was reversed by miR-326 inhibitors. The increase of PCAT6 induced the accumulation of ROS, mitochondrial and metabolic dysfunction in macrophages and mimics of miR-326 exhibited an opposite process. RohA has been recognized as a significant regulator of immune cell function. In our current work, we observed that RohA function as a downstream target for miR-326. In conclusion, our study highlighted a significant role of PCAT6/miR-326/RohA in immune response of macrophages in CCA and indicated PCAT6 as a potential target of immunotherapy in CCA.
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Affiliation(s)
- Jianfei Tu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Fazong Wu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Li Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Liyun Zheng
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Yang Yang
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Xihui Ying
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Jingjing Song
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Chunmiao Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China
| | - Xianghua Hu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China
| | - Zhongwei Zhao
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Affiliated Lishui Hospital of Zhejiang University/Clinical College of The Affiliated Central Hospital of Lishui University, Lishui, China.,Department of Interventional Diagnosis and Treatment, The Central Hospital of Zhejiang Lishui, Lishui, China
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Jiang J, Lin H, Shi S, Hong Y, Bai X, Cao X. Hsa_circRNA_0000518 facilitates breast cancer development via regulation of the miR-326/FGFR1 axis. Thorac Cancer 2020; 11:3181-3192. [PMID: 33000910 PMCID: PMC7606003 DOI: 10.1111/1759-7714.13641] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/10/2020] [Accepted: 08/11/2020] [Indexed: 12/11/2022] Open
Abstract
Background Breast cancer (BC) is a heterogeneous malignant tumor that threatens the health of women worldwide. Hsa_circRNA_0000518 (circ_0000518) has been revealed to be upregulated in BC tissues. However, the role and mechanism of circ_0000518 in BC are indistinct. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was implemented to detect the levels of circ_0000518, microRNA (miR)‐326, and fibroblast growth factor receptor 1 (FGFR1) mRNA in BC tissues and cells. Cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, and transwell assays were executed to estimate BC cell proliferation, cell cycle progression, apoptosis, migration, and invasion. The relationship between circ_0000518 or FGFR1 and miR‐326 was verified by dual‐luciferase reporter and/or RNA immunoprecipitation (RIP) assays. The role of circ_0000518 in vivo was confirmed by xenograft assay. Results Circ_0000518 and FGFR1 were upregulated while miR‐326 was downregulated in BC tissues and cells. Circ_0000518 silencing impeded tumor growth in vivo and induced cell cycle arrest, apoptosis, cured proliferation, colony formation, migration, and invasion of BC cells in vitro. Circ_0000518 regulated FGFR1 expression via competitively binding to miR‐326 in BC cells. MiR‐326 inhibitor reversed the inhibitory influence of circ_0000518 knockdown on the malignant behaviors of BC cells. FGFR1 overexpression abolished miR‐326 mimic‐mediated influence on the malignant behaviors of BC cells. Conclusions Circ_0000518 facilitated BC development via regulation of the miR‐326/FGFR1 axis, suggesting that circ_0000518 might be a promising target for BC treatment.
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Affiliation(s)
- Jing Jiang
- The First Department of Breast Cancer, Tianjin Medical University Cancer Institute Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Department of Breast Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Hui Lin
- The First Department of Breast Cancer, Tianjin Medical University Cancer Institute Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.,Department of Thyroid and Breast Surgery, Taizhou Hospital of Zhejiang Province Affiliated to WenZhou Medical University, Taizhou, China
| | - Shenghong Shi
- Department of Breast Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Ying Hong
- Department of Breast Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Xianan Bai
- Department of Breast Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China.,Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
| | - Xuchen Cao
- The First Department of Breast Cancer, Tianjin Medical University Cancer Institute Hospital, National Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.,Tianjin's Clinical Research Center for Cancer, Tianjin, China.,Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China
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Fan Z, Bai Y, Zhang Q, Qian P. CircRNA circ_POLA2 promotes lung cancer cell stemness via regulating the miR-326/GNB1 axis. ENVIRONMENTAL TOXICOLOGY 2020; 35:1146-1156. [PMID: 32511866 DOI: 10.1002/tox.22980] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 05/09/2020] [Accepted: 05/18/2020] [Indexed: 06/11/2023]
Abstract
Circular RNAs (CircRNAs) are a group of noncoding RNAs that have essential function in the development and progression of various cancers. The expression pattern and function of circRNA in lung cancer is not fully understood. In the present study, we aimed to investigate the expression profiles and underlying mechanism of circRNA circ_POLA2 in lung cancer cell stemness. Circ_POLA2 was highly expressed in lung cancer tissues and predicted a poor prognosis in lung cancer patients. Knockdown of circ_POLA2 inhibited the stemness of lung cancer cells, which is evident by the decreased sphere-formation ability, ALDH1 activity, and stemness marker expression, but had no effects on cell viability. Mechanistically, circ_POLA2 functioned as a ceRNA by sponging miR-326. Furthermore, miR-326 negatively regulated G protein subunit beta 1 (GNB1) expression by targeting its 3'-UTR (untranslated region). Intriguingly, we found that GNB1 was overexpressed and associated with poor prognosis in lung cancer patients. Overexpression of GNB1 could antagonize the inhibitory effect of circ_POLA2 knockdown on lung cancer cell stemness. In conclusion, circ_POLA2 promotes lung cancer cell stemness and progression via regulating the miR-326/GNB1 axis, which might serve as a novel therapeutic target for lung cancer patients.
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Affiliation(s)
- Zhaohui Fan
- Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Yongkang Bai
- Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Qian Zhang
- Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
| | - Pudong Qian
- Department of Radiotherapy, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China
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PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs. Life Sci 2020; 256:117899. [DOI: 10.1016/j.lfs.2020.117899] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 05/31/2020] [Accepted: 05/31/2020] [Indexed: 02/07/2023]
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Xu T, Wang M, Jiang L, Ma L, Wan L, Chen Q, Wei C, Wang Z. CircRNAs in anticancer drug resistance: recent advances and future potential. Mol Cancer 2020; 19:127. [PMID: 32799866 PMCID: PMC7429705 DOI: 10.1186/s12943-020-01240-3] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 07/31/2020] [Indexed: 12/13/2022] Open
Abstract
CircRNAs are a novel class of RNA molecules with a unique closed continuous loop structure. CircRNAs are abundant in eukaryotic cells, have unique stability and tissue specificity, and can play a biological regulatory role at various levels, such as transcriptional and posttranscriptional levels. Numerous studies have indicated that circRNAs serve a crucial purpose in cancer biology. CircRNAs regulate tumor behavioral phenotypes such as proliferation and migration through various molecular mechanisms, such as miRNA sponging, transcriptional regulation, and protein interaction. Recently, several reports have demonstrated that they are also deeply involved in resistance to anticancer drugs, from traditional chemotherapeutic drugs to targeted and immunotherapeutic drugs. This review is the first to summarize the latest research on circRNAs in anticancer drug resistance based on drug classification and to discuss their potential clinical applications.
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Affiliation(s)
- Tianwei Xu
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China
| | - Mengwei Wang
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China
| | - Lihua Jiang
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China
| | - Li Ma
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China
| | - Li Wan
- Department of Oncology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, 223300, Jiangsu, China
| | - Qinnan Chen
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China
| | - Chenchen Wei
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China.
| | - Zhaoxia Wang
- Cancer Medical Center, The Second Affiliated Hospital of Nanjing Medical University, Jiangjiayuan road 121#, Nanjing, 210011, Jiangsu, P.R. China.
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Ashrafizadeh M, Hushmandi K, Hashemi M, Akbari ME, Kubatka P, Raei M, Koklesova L, Shahinozzaman M, Mohammadinejad R, Najafi M, Sethi G, Kumar AP, Zarrabi A. Role of microRNA/Epithelial-to-Mesenchymal Transition Axis in the Metastasis of Bladder Cancer. Biomolecules 2020; 10:E1159. [PMID: 32784711 PMCID: PMC7464913 DOI: 10.3390/biom10081159] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 08/03/2020] [Accepted: 08/05/2020] [Indexed: 12/12/2022] Open
Abstract
Bladder cancer (BC) is the 11th most common diagnosed cancer, and a number of factors including environmental and genetic ones participate in BC development. Metastasis of BC cells into neighboring and distant tissues significantly reduces overall survival of patients with this life-threatening disorder. Recently, studies have focused on revealing molecular pathways involved in metastasis of BC cells, and in this review, we focus on microRNAs (miRNAs) and their regulatory effect on epithelial-to-mesenchymal transition (EMT) mechanisms that can regulate metastasis. EMT is a vital process for migration of BC cells, and inhibition of this mechanism restricts invasion of BC cells. MiRNAs are endogenous non-coding RNAs with 19-24 nucleotides capable of regulating different cellular events, and EMT is one of them. In BC cells, miRNAs are able to both induce and/or inhibit EMT. For regulation of EMT, miRNAs affect different molecular pathways such as transforming growth factor-beta (TGF-β), Snail, Slug, ZEB1/2, CD44, NSBP1, which are, discussed in detail this review. Besides, miRNA/EMT axis can also be regulated by upstream mediators such as lncRNAs, circRNAs and targeted by diverse anti-tumor agents. These topics are also discussed here to reveal diverse molecular pathways involved in migration of BC cells and strategies to target them to develop effective therapeutics.
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Affiliation(s)
- Milad Ashrafizadeh
- Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran;
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1419963114, Iran;
| | - Mehrdad Hashemi
- Department of Genetics, Faculty of advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran;
| | - Mohammad Esmaeil Akbari
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran 1989934148, Iran;
| | - Peter Kubatka
- Department of Medical Biology and Division of Oncology—Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Mehdi Raei
- Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran;
| | - Lenka Koklesova
- Department of Obstetrics and Gynecology, Martin University Hospital and Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia;
| | - Md Shahinozzaman
- Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA;
| | - Reza Mohammadinejad
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 55877577, Iran;
| | - Masoud Najafi
- Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran;
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore;
| | - Alan Prem Kumar
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore;
- Cancer Science Institute of Singapore, Centre for Translational Medicine, 14 Medical Drive, #11-01M, Singapore 117599, Singapore
| | - Ali Zarrabi
- Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul 34956, Turkey
- Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, Istanbul 34956, Turkey
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