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Kawamura J, Yamakuchi M, Ueno K, Hashiguchi T, Okamoto Y. MiR-25-3p regulates pulmonary arteriovenous malformation after Glenn procedure in patients with univentricular heart via the PHLPP2-HIF-1α axis. Sci Rep 2025; 15:4138. [PMID: 39900983 PMCID: PMC11790876 DOI: 10.1038/s41598-025-88840-5] [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: 08/21/2024] [Accepted: 01/31/2025] [Indexed: 02/05/2025] Open
Abstract
The detailed mechanism of pulmonary arteriovenous malformations after Glenn surgery (G-PAVMs) in cyanotic congenital heart disease (CHD) remains unclear. Microarray in situ hybridization was performed to assess the miRNA (miRNA) profiles of serum from pediatric patients (0-6 years of age) with G-PAVMs and after the Fontan procedure without G-PAVMs. In addition, we investigated the tube formation, migration, and proliferation of human lung microvascular endothelial cells (HMVEC-L) transfected with miR-25-3p mimic, miR-25-3p inhibitor, or PHLPP2 small interfering RNA, and examined HIF-1α/VEGF-A signaling after hypoxic stimulation. Serum miRNAs that showed ≥ 2-fold higher levels in patients with G-PAVMs than in other patients were selected. MiR-25-3p was significantly upregulated in the pulmonary artery sera of the post-Glenn group than in the post-Fontan group. We identified PHLPP2 as a direct target of miR-25-3p. PHLPP2 expression was significantly decreased in HMVEC-L transfected with miR-25-3p mimic compared to the control cells. HIF-1α and VEGF-A expression levels were increased in HMVEC-L transfected with miR-25-3p mimic compared to the control cells in a PHLPP2/Akt/mTOR signaling-dependent manner after hypoxic stimulation. MiR-25-3p promoted HMVEC-L angiogenesis, proliferation, and migration under hypoxic conditions. MiR-25-3p in the pulmonary arteries may contribute to G-PAVM development.
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Affiliation(s)
- Junpei Kawamura
- Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Munekazu Yamakuchi
- Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan.
| | - Kentaro Ueno
- Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Teruto Hashiguchi
- Department of Laboratory and Vascular Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 890-8544, Japan
| | - Yasuhiro Okamoto
- Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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Chen Y, Chen B, Tu S, Yuan H. miR‑25‑3p serves as an oncogenic in colorectal cancer cells by regulating the ubiquitin ligase FBXW7 function. Oncol Rep 2024; 52:153. [PMID: 39329268 PMCID: PMC11450686 DOI: 10.3892/or.2024.8812] [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: 01/14/2024] [Accepted: 06/12/2024] [Indexed: 09/28/2024] Open
Abstract
Accumulating evidence indicates that the dysregulation of microRNAs (miRNAs or miRs), is associated with human malignancies and suggests a casual role of miRNAs in tumor initiation and progression. Even though it has been discovered that a number of miRNAs play significant parts in the development of colorectal cancer (CRC), it is crucial to comprehend the regulatory functions that other miRNAs play in CRC. Based on GSE183437 and GSE156719 microarray data that were obtained from Gene Expression Omnibus database, candidate miRNAs were researched. The oncogenic effects of miR‑25‑3p in different malignancies have led to its selection for additional investigation in the present study. The expression of miR‑25‑3p was verified by reverse transcription‑quantitative PCR, and its correlation with clinicopathological characteristics in patients with CRC was then investigated. In vitro assays were conducted to investigate the influence of miR‑25‑3p on the proliferative and apoptotic behaviors of HCT116 and Caco‑2 cells. The present data revealed that miR‑25‑3p exhibited one of the most significant upregulations in CRC tissues and cell lines. The expression levels of miR‑25‑3p were found to be intimately correlated with tumor size, distant metastasis, tumor‑node‑metastasis stage, and shorter overall survival rate. In terms of functionality, the downregulation of miR‑25‑3p led to the inhibition of cellular proliferation and the enhancement of apoptosis in both HCT116 and Caco‑2 cell lines. The critical tumor suppressor F‑box and WD repeat containing domain 7 (FBXW7) was identified as a direct molecular target for miR‑25‑3p, with an inverse relationship observed between the two in neoplastic tissues. Subsequent studies demonstrated that the tumor suppressive effects of miR‑25‑3p inhibitor were effectively negated by the silencing of FBXW7. Moreover, the ability of FBXW7 to inhibit the expression of several oncogenes was deemed essential for countering the anticancer effects mediated by miR‑25‑3p downregulation. These findings posit miR‑25‑3p as a promising therapeutic target and prognostic indicator for CRC.
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Affiliation(s)
- Yanbin Chen
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Bingchen Chen
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Shiliang Tu
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Hang Yuan
- General Surgery, Cancer Center, Department of Colorectal Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
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Liu G, Tian J. PAX8-AS1/microRNA-25-3p/LATS2 regulates malignant progression of ovarian cancer via Hippo signaling. Mutat Res 2024; 829:111858. [PMID: 38788314 DOI: 10.1016/j.mrfmmm.2024.111858] [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: 02/21/2024] [Revised: 03/27/2024] [Accepted: 04/18/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND Ovarian cancer (OC) is a frequent malignancy of the female reproductive system. Recently, the aberrant expression of numerous lncRNAs has been confirmed as a key factor for cancer development. The regulatory role of PAX8-AS1 in some cancers has been investigated, but its role in OC progression remains unclear. This study focuses on the role and molecular mechanism of PAX8-AS1 in the malignant progression of OC. METHODS Bioinformatics means were adopted to analyze the expression of PAX8-AS1, microRNA-25-3p, and LATS2 in OC tissues and the binding sites between the three. qRT-PCR was employed to determine the expression of these genes in OC cells. CCK-8, colony formation, scratch healing, and Transwell assays were used to see cell viability, proliferation, migration, and invasion, respectively. Fluorescence in situ Hybridization was performed to probe the subcellular localization of PAX8-AS1. Western blot was applied to evaluate the expression and phosphorylation levels of YAP and TAZ, and an immunofluorescence assay was used to detect the translocation of them. Dual luciferase assay was applied to validate the binding relationship between PAX8-AS1 and microRNA-25-3p, as well as between microRNA-25-3p and LATS2. RESULTS PAX8-AS1 and LATS2 were lowly expressed. MicroRNA-25-3p was highly expressed in OC. PAX8-AS1 was expressed in cytoplasm and regulated LATS2 expression by sponging microRNA-25-3p. Overexpressing PAX8-AS1 can suppress the malignant behaviors of OC cells, whereas treatment with microRNA-mimic can reverse these results. In addition, the phosphorylation levels of YAP and TAZ increased upon oe-LATS2 treatment, and oe-LATS2 could promote YAP and TAZ translocate from the nucleus to cytoplasm. Rescue experiments demonstrated that sh-PAX8-AS1 fostered malignant progression of OC, which was reversed by simultaneous oe-LATS2. CONCLUSION In summary, PAX8-AS1/microRNA-25-3p/LATS2 regulated the malignant progression of OC through Hippo signaling, which suggested that PAX8-AS1/microRNA-25-3p/LATS2 axis may be a novel target for OC treatment.
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Affiliation(s)
- Gang Liu
- Department of Gynaecology, University-Town Hospital of Chongqing Medical University, Chongqing 400000, China
| | - Jing Tian
- Department of Gynaecology, University-Town Hospital of Chongqing Medical University, Chongqing 400000, China.
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Zhao P, Cheng J, Li B, Nie D, Wang H, Li C, Gui S, Zhang Y. Retraction Note: LncRNA PCAT6 regulates the progression of pituitary adenomas by regulating the miR-139-3p/BRD4 axis. Cancer Cell Int 2024; 24:211. [PMID: 38877476 PMCID: PMC11179393 DOI: 10.1186/s12935-024-03398-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2024] [Indexed: 06/16/2024] Open
Affiliation(s)
- Peng Zhao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China.
| | - Jianhua Cheng
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China
| | - Bin Li
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China
| | - Ding Nie
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China
| | - Hongyun Wang
- Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Chuzhong Li
- Beijing Tiantan Hospital, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People's Republic of China
| | - Songbai Gui
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China
| | - Yazhuo Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China
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Cong M, Li J, Wang L, Liu C, Zheng M, Zhou Q, Du M, Ye X, Feng M, Ye Y, Zhang S, Xu W, Lu Y, Wang C, Xia Y, Xie H, Zhang Y, He Q, Gong L, Gu Y, Sun H, Zhang Q, Zhao J, Ding F, Gu X, Zhou S. MircoRNA-25-3p in skin precursor cell-induced Schwann cell-derived extracellular vesicles promotes axon regeneration by targeting Tgif1. Exp Neurol 2024; 376:114750. [PMID: 38492636 DOI: 10.1016/j.expneurol.2024.114750] [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: 12/08/2023] [Revised: 02/20/2024] [Accepted: 03/08/2024] [Indexed: 03/18/2024]
Abstract
Nerve injury often leads to severe dysfunction because of the lack of axon regeneration in adult mammal. Intriguingly a series of extracellular vesicles (EVs) have the obvious ability to accelerate the nerve repair. However, the detailed molecular mechanisms to describe that EVs switch neuron from a transmitter to a regenerative state have not been elucidated. This study elucidated the microRNA (miRNA) expression profiles of two types of EVs that promote nerve regeneration. The functions of these miRNAs were screened in vitro. Among the 12 overlapping miRNAs, miR-25-3p was selected for further analysis as it markedly promoted axon regeneration both in vivo and in vitro. Furthermore, knockdown experiments confirmed that PTEN and Klf4, which are the major inhibitors of axon regeneration, were the direct targets of miR-25-3p in dorsal root ganglion (DRG) neurons. The utilization of luciferase reporter assays and functional tests provided evidence that miR-25-3p enhances axon regeneration by targeting Tgif1. Additionally, miR-25-3p upregulated the phosphorylation of Erk. Furthermore, Rapamycin modulated the expression of miR-25-3p in DRG neurons. Finally, the pro-axon regeneration effects of EVs were confirmed by overexpressing miR-25-3p and Tgif1 knockdown in the optic nerve crush model. Thus, the enrichment of miR-25-3p in EVs suggests that it regulates axon regeneration, proving a potential cell-free treatment strategy for nerve injury.
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Affiliation(s)
- Meng Cong
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Jiyu Li
- Department of Orthopedic Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Lijuan Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Chang Liu
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Mengru Zheng
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Qiang Zhou
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Mingzhi Du
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Xinli Ye
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Min Feng
- Department of Orthopedic Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China
| | - Yujiao Ye
- Medical School of Nantong University, Nantong, Jiangsu 226001, China
| | - Shuyu Zhang
- Medical School of Nantong University, Nantong, Jiangsu 226001, China
| | - Wenqing Xu
- Medical School of Nantong University, Nantong, Jiangsu 226001, China
| | - Yi Lu
- Medical School of Nantong University, Nantong, Jiangsu 226001, China
| | - Cheng Wang
- Medical School of Nantong University, Nantong, Jiangsu 226001, China
| | - Yingjie Xia
- Medical School of Nantong University, Nantong, Jiangsu 226001, China
| | - Huimin Xie
- The Affiliated Nantong Stomatological Hospital of Nantong University, Nantong 226007, China
| | - Yide Zhang
- Department of Geriatrics, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China
| | - Qianru He
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Leilei Gong
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Yun Gu
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Hualin Sun
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Qi Zhang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China
| | - Jian Zhao
- Department of Orthopedic Oncology, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, China.
| | - Fei Ding
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China.
| | - Xiaosong Gu
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China.
| | - Songlin Zhou
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, Jiangsu 226001, China.
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Kim MJ, Lim SG, Cho DH, Lee JY, Suk K, Lee WH. Regulation of inflammatory response by LINC00346 via miR-25-3p-mediated modulation of the PTEN/PI3K/AKT/NF-κB pathway. Biochem Biophys Res Commun 2024; 709:149828. [PMID: 38537596 DOI: 10.1016/j.bbrc.2024.149828] [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: 12/15/2023] [Revised: 03/16/2024] [Accepted: 03/24/2024] [Indexed: 04/13/2024]
Abstract
Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively. Analyses using dual luciferase assay and decoy RNAs that could block RNA-RNA interactions indicated that LINC00346 improves phosphatase and tensin homolog (PTEN) expression by sponging miR-25-3p. Subsequently, PTEN suppresses phosphoinositide-3 kinase (PI3K)-mediated conversion of phosphatidylinositol-4,5-bisphosphate (PIP2) into phosphatidylinositol-3,4,5-trisphosphate (PIP3) as well as consequent activation of protein kinase B (AKT) and NF-κB. Interestingly, database analysis revealed that the expression levels of LINC00346 and PTEN were simultaneously decreased in breast cancer tissues. Further analyses conducted using a breast cancer cell line, MDA-MB-231, confirmed the functional relationship among LINC00346, miR-25-3p, and PTEN in LPS-induced activation of NF-κB. These results indicate that miR-25-3p-sponging activity of LINC00346 affects the balance between PTEN and PI3K as well as the downstream activation of AKT/NF-κB pathway in inflammatory conditions.
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Affiliation(s)
- Min-Ji Kim
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Su-Geun Lim
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Dong-Hyung Cho
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Jun-Yeong Lee
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Kyoungho Suk
- Department of Pharmacology, Brain Science & Engineering Institute, BK21 FOUR KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, 41944, Republic of Korea
| | - Won-Ha Lee
- School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea.
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Rahimipour Anaraki S, Farzami P, Hosseini Nasab SS, Kousari A, Fazlollahpour Naghibi A, Shariat Zadeh M, Barati R, Taha SR, Karimian A, Nabi-Afjadi M, Yousefi B. Natural products and the balancing act of autophagy-dependent/independent ferroptosis in cancer therapy. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:2531-2549. [PMID: 37878043 DOI: 10.1007/s00210-023-02782-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 10/11/2023] [Indexed: 10/26/2023]
Abstract
The control of biological cell death is essential for the body's appropriate growth. The resistance of cells to the apoptotic process presents a new difficulty in the treatment of cancer. To combat cancer cells, researchers are working to find new apoptotic pathways and components to activate. One of the processes of regulated cell death (RCD) is referred to as ferroptosis marked by a decline in the activity of lipid glutathione peroxidase 4 (GPX4) after the buildup of reactive oxygen species (ROS). Since lipid peroxidation is a crucial component of ferroptosis and is required for its start, numerous medicines have been studied, particularly for the treatment of cancer. In this context, autophagy is an additional form of RCD that can govern ferroptosis through shared signaling pathways/factors involved in both mechanisms. In this review, we will explore the molecular mechanisms underlying ferroptosis and its association with autophagy, to gain fresh insights into their interplay in cancer advancement, and the potential of natural products for its treatment.
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Affiliation(s)
| | - Payam Farzami
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Ali Kousari
- Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Andarz Fazlollahpour Naghibi
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | | | - Reza Barati
- Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Taha
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Ansar Karimian
- Faculty of Medicine, Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Bahman Yousefi
- Faculty of Medicine, Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Wei QY, Jin F, Wang ZY, Li BJ, Cao WB, Sun ZY, Mo SJ. MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:1497-1523. [PMID: 38617454 PMCID: PMC11008420 DOI: 10.3748/wjg.v30.i11.1497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/12/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.
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Affiliation(s)
- Qi-Ying Wei
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Feng Jin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhong-Yu Wang
- Department of Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Bing-Jie Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Bo Cao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhi-Yan Sun
- Division of Special Service, Department of Basic Oncology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sai-Jun Mo
- Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Zhong W, Dong S, Wang H, Pan C, Yang S. Functional Mechanism of MicroRNA-25-3p in Hilar Cholangiocarcinoma Cell Proliferation and Migration Through Regulation of Dual Specificity Phosphatase 5. J INVEST SURG 2023; 36:2202768. [PMID: 37394525 DOI: 10.1080/08941939.2023.2202768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 03/15/2023] [Accepted: 04/06/2023] [Indexed: 07/04/2023]
Abstract
OBJECTIVE Hilar cholangiocarcinoma (HCCA) is a highly aggressive biliary tract tumor. microRNAs (miRs) exert dual actions in various cancers. This paper seeks to expound on the functional mechanisms of miR-25-3p/dual specificity phosphatase 5 (DUSP5) in HCCA cell proliferation and migration. METHODS HCCA-related data were downloaded from GEO database to screen out differentially-expressed genes. The potential target miR (miR-25-3p) and its expression in HCCA were analyzed on Starbase. The binding relation between miR-25-3p and DUSP5 was confirmed by dual-luciferase assay. Levels of miR-25-3p and DUSP5 in FRH-0201 cells and HIBEpics were determined by RT-qPCR and Western blot. miR-25-3p and DUSP5 levels were intervened with to explore their effects on FRH-0201 cells. The apoptosis, proliferation, migration, and invasion of FRH-0201 cells were evaluated by TUNEL, CCK8, scratch healing, and Transwell assays. Flow cytometry was conducted to assess FRH-0201 cell cycle. Levels of cell cycle-related proteins were determined by Western blot. RESULTS DUSP5 was weakly-expressed and miR-25-3p was highly-expressed in HCCA samples and cells. miR-25-3p targeted DUSP5. miR-25-3p suppressed FRH-0201 cell apoptosis and increased cell proliferation, migration, and invasion. DUSP5 overexpression partially abrogated miR-25-3p overexpression-exerted effects on FRH-0201 cells. miR-25-3p stimulated G1/S phase transition of FRH-0201 cells by targeting DUSP5. CONCLUSION miR-25-3p regulated HCCA cell cycle and facilitated cell proliferation and migration by targeting DUSP5.
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Affiliation(s)
- Wan Zhong
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Shiyang Dong
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Han Wang
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Chao Pan
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Shiyong Yang
- Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Lu Q, Sun H, Yu Q, Tang D. Circ_PRDM5/miR-25-3p/ANKRD46 axis is associated with cell malignant behaviors in subjects with breast cancer evaluated by ultrasound. J Biochem Mol Toxicol 2023; 37:e23469. [PMID: 37485755 DOI: 10.1002/jbt.23469] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Revised: 06/20/2023] [Accepted: 07/08/2023] [Indexed: 07/25/2023]
Abstract
Circular RNAs (circRNAs) are key RNA molecules in cancer biology. CircRNA PR/SET domain 5 (circ_PRDM5, hsa_circ_0005654) was downregulated in breast cancer (BC) tissues. This study is designed to investigate the functional mechanism of circ_PRDM5 in BC. Ultrasound examinations were performed to evaluate BC patients and normal individuals. Circ_PRDM5, miR-25-3p, and Ankyrin repeat domain 46 (ANKRD46) level detection was carried out by reverse transcription-quantitative polymerase chain reaction. 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay was used for cell viability examination. Cell proliferation was evaluated by ethynyl-2'-deoxyuridine assay and colony formation assay. The protein levels were examined using western blot. Cell migration and invasion abilities were assessed via transwell assay. Target interaction was analyzed via dual-luciferase reporter assay. The role of circ_PRDM5 in vivo was explored via xenograft tumor assay. Circ_PRDM5 expression was downregulated in BC tissues and cells. Overexpression of circ_PRDM5 suppressed proliferation and motility but enhanced apoptosis of BC cells. Circ_PRDM5 served as a sponge of miR-25-3p. Circ_PRDM5 impeded BC cell malignant development via sponging miR-25-3p. Circ_PRDM5 induced ANKRD46 upregulation by targeting miR-25-3p. Inhibition of miR-25-3p retarded BC progression by increasing the ANKRD46 level. Circ_PRDM5 repressed BC tumorigenesis in vivo through mediating the miR-25-3p/ANKRD46 axis. This study evidenced that circ_PRDM5 inhibited cell progression and tumor growth in BC via interacting with mir-25-3p/ANKRD46 network.
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Affiliation(s)
- Qin Lu
- The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Huihui Sun
- The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu, China
| | - Qian Yu
- Huai'an Maternal and Child Health Hospital, Huai'an, Jiangsu, China
| | - Dongdong Tang
- Huaiyin Hospital of Huai'an City, Huai'an, Jiangsu, China
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11
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Liu Y, Hu Y, Zhao C, Lu Q. CircRNA B cell linker regulates cisplatin sensitivity in nonsmall cell lung cancer via microRNA-25-3p/BarH‑like homeobox 2 axis. Anticancer Drugs 2023; 34:640-651. [PMID: 36602424 DOI: 10.1097/cad.0000000000001349] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Cisplatin (DDP) was a commonly used drug in the treatment of nonsmall cell lung cancer (NSCLC). However, the current resistance of patients to DDP seriously affected its therapeutic effect. Circular RNAs (circRNAs) have been reported to regulate drug resistance in cells. The purpose of this paper is to study the effect of circRNA B cell linker (circ_BLNK) in DDP resistance of NSCLC. The abundances of circ_BLNK, microRNA-25-3p (miR-25-3p) and BarH‑like homeobox 2 (BARX2) were examined by quantitative real-time PCR and western blot analysis. Cell proliferation and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, EdU assay and flow cytometry. Transwell assay was applied to assess cell migration and invasion. Protein levels were quantified by western blot analysis. Dual-luciferase reporter assay was enforced to confirm the links among circ_BLNK, miR-25-3p and BARX2. The mice models were enforced to evaluate tumorigenicity. Herein, circ_BLNK and BARX2 were lower-expressed, whereas miR-25-3p was higher-expressed in A549/DDP and H1299/DDP cells than their homologous parental NSCLC cells. Circ_BLNK increases improved DDP sensitivity of NSCLC cells by promoting cell apoptosis and inhibiting proliferation, migration and invasion. Moreover, we confirmed that circ_BLNK regulated BARX2 by inhibiting miR-25-3p. Accordingly, overexpression of circ_BLNK improved DDP sensitivity of NSCLC cells via miR-25-3p/BARX2 axis. Besides, circ_BLNK reduced cell resistance to DDP, thereby inhibiting tumor development in mice. Circ_BLNK promoted the DDP sensitivity of NSCLC via regulating miR-25-3p/BARX2 axis.
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Affiliation(s)
- Yi Liu
- Departments of Thoracic Surgery
| | | | - Chong Zhao
- Respiratory and Critical Care Medicine, Yichun People' s Hospital & The Affiliated Yichun Hospital of Nanchang University, Yichang, China
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12
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Doghish AS, El-Husseiny AA, Abdelmaksoud NM, El-Mahdy HA, Elsakka EGE, Abdel Mageed SS, Mahmoud AMA, Raouf AA, Elballal MS, El-Dakroury WA, AbdelRazek MMM, Noshy M, El-Husseiny HM, Abulsoud AI. The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer. Pathol Res Pract 2023; 246:154529. [PMID: 37196470 DOI: 10.1016/j.prp.2023.154529] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/06/2023] [Accepted: 05/08/2023] [Indexed: 05/19/2023]
Abstract
Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-β signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.
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Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, 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
| | - Nourhan M Abdelmaksoud
- Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Hesham A El-Mahdy
- 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
| | - Sherif S Abdel Mageed
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Abdulla M A Mahmoud
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Ahmed Amr Raouf
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohammed S Elballal
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Walaa A El-Dakroury
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mohamed M M AbdelRazek
- Department of Pharmacognosy, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt
| | - Mina Noshy
- Clinical Pharmacy Department, Faculty of Pharmacy, King Salman International University (KSIU), SouthSinai, Ras Sudr 46612, 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
| | - Ahmed I Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry and Biotechnology, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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13
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Qi F, Shen W, Wei X, Cheng Y, Xu F, Zheng Y, Li L, Qin C, Li X. CSNK1D-mediated phosphorylation of HNRNPA2B1 induces miR-25-3p/miR-93-5p maturation to promote prostate cancer cell proliferation and migration through m 6A-dependent manner. Cell Mol Life Sci 2023; 80:156. [PMID: 37208565 PMCID: PMC11072693 DOI: 10.1007/s00018-023-04798-5] [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: 01/13/2023] [Revised: 04/18/2023] [Accepted: 05/04/2023] [Indexed: 05/21/2023]
Abstract
It has been reported that heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is highly expressed in prostate cancer (PCa) and associated with poor prognosis of patients with PCa. Nevertheless, the specific mechanism underlying HNRNPA2B1 functions in PCa remains not clear. In our study, we proved that HNRNPA2B1 promoted the progression of PCa through in vitro and in vivo experiments. Further, we found that HNRNPA2B1 induced the maturation of miR-25-3p/miR-93-5p by recognizing primary miR-25/93 (pri-miR-25/93) through N6-methyladenosine (m6A)-dependent manner. In addition, both miR-93-5p and miR-25-3p were proven as tumor promoters in PCa. Interestingly, by mass spectrometry analysis and mechanical experiments, we found that casein kinase 1 delta (CSNK1D) could mediate the phosphorylation of HNRNPA2B1 to enhance its stability. Moreover, we further proved that miR-93-5p targeted BMP and activin membrane-bound inhibitor (BAMBI) mRNA to reduce its expression, thereby activating transforming growth factor β (TGF-β) pathway. At the same time, miR-25-3p targeted forkhead box O3 (FOXO3) to inactivate FOXO pathway. These results collectively indicated that CSNK1D stabilized HNRNPA2B1 facilitates the processing of miR-25-3p/miR-93-5p to regulate TGF-β and FOXO pathways, resulting in PCa progression. Our findings supported that HNRNPA2B1 might be a promising target for PCa treatment.
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Affiliation(s)
- Feng Qi
- Department of Urologic Surgery, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Wenyi Shen
- Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiyi Wei
- State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yifei Cheng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Fan Xu
- Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Yuxiao Zheng
- Department of Urologic Surgery, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China
| | - Lu Li
- State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd, Nanjing, China
- Nanjing Simcere Medical Laboratory Science Co., Ltd, Nanjing, China
| | - Chao Qin
- State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Xiao Li
- Department of Urologic Surgery, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
- Department of Scientific Research, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
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14
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Lenda B, Żebrowska-Nawrocka M, Turek G, Balcerczak E. Zinc Finger E-Box Binding Homeobox Family: Non-Coding RNA and Epigenetic Regulation in Gliomas. Biomedicines 2023; 11:biomedicines11051364. [PMID: 37239035 DOI: 10.3390/biomedicines11051364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/26/2023] [Accepted: 05/03/2023] [Indexed: 05/28/2023] Open
Abstract
Gliomas are the most common malignant brain tumours. Among them, glioblastoma (GBM) is a grade four tumour with a median survival of approximately 15 months and still limited treatment options. Although a classical epithelial to mesenchymal transition (EMT) is not the case in glioma due to its non-epithelial origin, the EMT-like processes may contribute largely to the aggressive and highly infiltrative nature of these tumours, thus promoting invasive phenotype and intracranial metastasis. To date, many well-known EMT transcription factors (EMT-TFs) have been described with clear, biological functions in glioma progression. Among them, EMT-related families of molecules such as SNAI, TWIST and ZEB are widely cited, well-established oncogenes considering both epithelial and non-epithelial tumours. In this review, we aimed to summarise the current knowledge with a regard to functional experiments considering the impact of miRNA and lncRNA as well as other epigenetic modifications, with a main focus on ZEB1 and ZEB2 in gliomas. Although we explored various molecular interactions and pathophysiological processes, such as cancer stem cell phenotype, hypoxia-induced EMT, tumour microenvironment and TMZ-resistant tumour cells, there is still a pressing need to elucidate the molecular mechanisms by which EMT-TFs are regulated in gliomas, which will enable researchers to uncover novel therapeutic targets as well as improve patients' diagnosis and prognostication.
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Affiliation(s)
- Bartosz Lenda
- Laboratory of Molecular Diagnostics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, BRaIN Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
| | - Marta Żebrowska-Nawrocka
- Laboratory of Molecular Diagnostics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, BRaIN Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
| | - Grzegorz Turek
- Department of Neurosurgery, Bródnowski Masovian Hospital, Kondratowicza 8, 03-242 Warsaw, Poland
| | - Ewa Balcerczak
- Laboratory of Molecular Diagnostics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, BRaIN Laboratories, Medical University of Lodz, Czechoslowacka 4, 92-216 Lodz, Poland
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15
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Qin B, Bai Q, Yan D, Yin F, Zhu Z, Xia C, Yang Y, Zhao Y. Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer. J Enzyme Inhib Med Chem 2022; 37:1995-2003. [PMID: 35833378 PMCID: PMC9291647 DOI: 10.1080/14756366.2022.2098954] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 11/23/2022] Open
Abstract
A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.
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Affiliation(s)
- Bo Qin
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Qian Bai
- Department of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Dan Yan
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Fanxiang Yin
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Zhu Zhu
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Chaoyuan Xia
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Yang Yang
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Yi Zhao
- Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
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16
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SIX3 function in cancer: progression and comprehensive analysis. Cancer Gene Ther 2022; 29:1542-1549. [PMID: 35764712 DOI: 10.1038/s41417-022-00488-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 05/02/2022] [Accepted: 05/27/2022] [Indexed: 02/04/2023]
Abstract
The homeobox gene family encodes transcription factors that are essential for cell growth, proliferation, and differentiation, and its dysfunction is linked to tumor initiation and progression. Sine oculis homeobox (SIX) belongs to the homeobox gene family, with SIX3 being a core member. Recent studies indicate that SXI3 functions as a cancer suppressor or promoter, which is mainly dependent on SIX3's influence on the signal pathways that promote or inhibit cancer in cells. The low expression of SIX3 in most malignant tumors was confirmed by detailed studies, which could promote the cell cycle, proliferation, migration, and angiogenesis. The recovery or upregulation of SIX3 expression to suppress cancer is closely related to the direct or indirect inhibition of the Wnt pathway. However, in some malignancies, such as esophageal cancer and gastric cancer, SIX3 is a tumor-promoting factor, and repressing SIX3 improves patients' prognosis. This review introduces the research progress of SIX3 in tumors and gives a comprehensive analysis, intending to explain why SIX3 plays different roles in different cancers and provide new cancer therapy strategies.
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17
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Nothnick WB, Peterson R, Minchella P, Falcone T, Graham A, Findley A. The Relationship and Expression of miR-451a, miR-25-3p and PTEN in Early Peritoneal Endometriotic Lesions and Their Modulation In Vitro. Int J Mol Sci 2022; 23:5862. [PMID: 35682544 PMCID: PMC9180609 DOI: 10.3390/ijms23115862] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2022] [Revised: 05/16/2022] [Accepted: 05/18/2022] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND miR-451a can function as a tumor suppresser and has been shown to be elevated in both endometriotic lesion tissue and serum from women with endometriosis. To further explore the role of miR-451a in the pathophysiology of endometriosis, specifically, further evaluating its association with the tumor suppressor, phosphatase and tensin homolog (PTEN), we examined their expression in individual endometriotic lesion tissue to gain insight into their relationship and further explore if miR-451a regulates PTEN expression. METHODS A total of 55 red, peritoneal endometriotic lesions and matched eutopic endometrial specimens were obtained from 46 patients with endometriosis. miR-451a, miR-25-3p and PTEN mRNA levels were assessed by qRT-PCR and reported for each matched eutopic and ectopic sample. To evaluate miR-451a and miR-25-3p expression of miR-25-3p and PTEN, respectively, 12Z cells (endometriotic epithelial cell line) were transfected and miR-25-3p expression was assessed by qRT-PCR, while PTEN protein expression was assessed by Western blotting. RESULTS PTEN and miR-25-3p expression exhibited an inverse relationship, as did miR-25-3p and miR-451a in individual lesions. Over-expression of miR-451a in 12Z cells resulted in down-regulation of miR-25-3p, while up-regulation of miR-25-3p resulted in down-regulation of PTEN protein expression. CONCLUSIONS By assessing individual endometriotic lesion expression, we discovered an inverse relationship between miR-451a, miR-25-3p and PTEN, while in vitro cell transfection studies suggest that miR-451a may regulate PTEN expression via modulating miR-25-3p.
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Affiliation(s)
- Warren B. Nothnick
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; (R.P.); (P.M.); (A.G.)
- Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA;
- Institute for Reproduction and Perinatal Research, Center for Reproductive Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA
| | - Riley Peterson
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; (R.P.); (P.M.); (A.G.)
| | - Paige Minchella
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; (R.P.); (P.M.); (A.G.)
| | - Tommaso Falcone
- Cleveland Clinic, London E1 4DG, UK;
- Cleveland Clinic, Lerner College of Medicine, Cleveland, OH 44101, USA
| | - Amanda Graham
- Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA; (R.P.); (P.M.); (A.G.)
| | - Austin Findley
- Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS 66160, USA;
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18
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Qiu R, Wang W, Li J, Wang Y. Roles of PTEN inactivation and PD-1/PD-L1 activation in esophageal squamous cell carcinoma. Mol Biol Rep 2022; 49:6633-6645. [PMID: 35301651 DOI: 10.1007/s11033-022-07246-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 02/04/2022] [Accepted: 02/08/2022] [Indexed: 02/07/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and developing countries. The purpose of this review is to summarize the roles of inactivation of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), and activation of the programmed cell death protein 1 (PD-1) upon binding to its ligand (PD-L1) in the promotion of ESCC. Studies of ESCC performed in vitro and in vivo indicated that PTEN and PD-L1 function in the regulation of cell proliferation, invasion, and migration; the epithelial-mesenchymal transition; resistance to chemotherapy and radiotherapy; and the PI3K/AKT signaling pathway. Certain genetic variants of PTEN are related to susceptibility to ESCC, and PTEN and PD-L1 also function in ESCC progression and affect the prognosis of patients with ESCC. There is also evidence that the expression of PD-L1 and PTEN are associated with the progression of certain other cancers. Future studies should further examine the relationship of PD-L1 and PTEN and their possible interactions in ESCC.
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Affiliation(s)
- Rong Qiu
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei Province, P. R. China
| | - Wenxi Wang
- Department of Oncology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan Province, China
| | - Juan Li
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei Province, P. R. China
| | - Yuxiang Wang
- Department of Radiation Oncology, Fourth Hospital of Hebei Medical University, No. 12 Jian Kang Road, Shijiazhuang, Hebei Province, P. R. China.
- , No.12, Jiankang Road, 050011, Shijiazhuang, Hebei Province, China.
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19
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Song Y, Liu W, Zhao Y, Zang J, Gao H. Fumonisin B1 exposure induces apoptosis of human kidney tubular epithelial cells through regulating PTEN/PI3K/AKT signaling pathway via disrupting lipid raft formation. Toxicon 2021; 204:31-36. [PMID: 34740561 DOI: 10.1016/j.toxicon.2021.10.013] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 10/18/2021] [Accepted: 10/26/2021] [Indexed: 12/12/2022]
Abstract
Fumonisin B1 (FB1) is a fungal metabolite that causes a variety of toxicological effects to human and animals. In this study, we aimed to investigate the effects of FB1 on kidney injury and clarify the possible mechanism. Human kidney tubular epithelial cells (HK-2) were treated with FB1 for different concentrations. The results demonstrated that FB1 could suppress the viability of HK-2 cells. FB1 could lead to the apoptosis of HK-2 cells in a dose-dependent manner. Furthermore, treatment of FB1 could induce the production of ROS and MDA. And the levels of SOD and GSH were decreased by FB1. The expression of Caspase-3 and Bax increased markedly and BCL2 expression was decreased by FB1 treatment. In addition, FB1 treatment could up-regulate PTEN expression and down-regulate PI3K and AKT expression. Also, FB1 could disrupt lipid raft by decreasing sphingomyelin level. In conclusion, FB1 exposure induces apoptosis of HK-2 cells through regulating PTEN/PI3K/AKT signaling pathway via disrupting lipid raft formation.
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Affiliation(s)
- Yanyan Song
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, 130021, China
| | - Wei Liu
- Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, 130021, China
| | - Yao Zhao
- Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, 130021, China
| | - Junting Zang
- Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, 130021, China
| | - Hang Gao
- Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, 130021, China.
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20
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Chen H, Liu Y, Liu P, Dai Q, Wang P. LINC01094 promotes the invasion of ovarian cancer cells and regulates the Wnt/β-catenin signaling pathway by targeting miR-532-3p. Exp Ther Med 2021; 22:1228. [PMID: 34539824 PMCID: PMC8438678 DOI: 10.3892/etm.2021.10662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 06/04/2021] [Indexed: 12/14/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) participate in the development of ovarian cancer (OC). The present study aimed to explore the roles of long intergenic non-protein coding RNA 1094 (LINC01094) in OC. LINC01094 and microRNA (miR)-532-3p expression in OC tissues and cells were measured using reverse transcription-quantitative PCR. Cell migration and invasion were detected using wound healing assays and Transwell assays, respectively. The binding of LINC01094 or β-catenin to miR-126-5p was detected using a Dual-luciferase reporter assay, and protein expression was confirmed using western blot analysis. The expression level of LINC01094 in patients with OC was higher in OC tissues compared with in adjacent tissues, and LINC01094 was upregulated in OC cell lines. In addition, LINC01094 overexpression promoted the viability, migration, invasion and cell cycle progression of OC cells, and inhibited OC cell apoptosis. Moreover, LINC01094 negatively regulated miR-532-3p in OC cells and tissues. miR-532-3p overexpression decreased the viability, migration, invasion and cell cycle progression of OC cells alongside downregulation of Wnt/β-catenin signaling pathway protein expression, as well as increasing OC cell apoptosis. Inhibition of LINC01094 with small interfering (si)-LINC01094 and overexpression of LINC01094 respectively reversed the effect of miR-532-3p inhibitor and mimics on OC cells. miR-532-3p could directly target β-catenin, and miR-532-3p inhibitor increased β-catenin expression, while si-LINC01094 attenuated this effect. In addition, LINC01094 overexpression promoted tumor growth in vivo by regulating miR-532-3p. Taken together, LINC01094 promoted the growth, migration, invasion and Wnt/β-catenin signaling pathway expression of OC cells by modulating miR-532-3p.
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Affiliation(s)
- Haiyan Chen
- Department of Gynaecology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830011, P.R. China
| | - Yanlin Liu
- Department of Gynaecology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830011, P.R. China
| | - Ping Liu
- Department of Reproductive Medicine, Hainan West Central Hospital, Danzhou, Hainan 571799, P.R. China
| | - Qiuxiang Dai
- Department of Obstetrical and Gynecology, Hainan Modern Women and Children's Hospital, Haikou, Hainan 570300, P.R. China
| | - Peiliang Wang
- Department of Gynaecology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region 830011, P.R. China
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21
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Zhao X, Yang L, Qin L. Methyltransferase-like 3 (METTL3) attenuates cardiomyocyte apoptosis with myocardial ischemia-reperfusion (I/R) injury through miR-25-3p and miR-873-5p. Cell Biol Int 2021; 46:992. [PMID: 34553450 DOI: 10.1002/cbin.11706] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Methyltransferase-like 3 (METTL3) mediated N6 -methyladenosine (m6A) promotes microRNAs (miRNAs) maturation by processing the primary miRNAs, and METTL3 involves in regulating the development of various diseases, including myocardial ischemia-reperfusion (I/R) injury. However, up until now, the association between METTL3 regulated miRNAs and I/R injury is not fully investigated, which makes investigations on this academic issue necessary. In this study, we showed that METTL3 was downregulated in mice I/R myocardial tissues and hypoxic/re-oxygenated (H/R) cardiomyocytes, and upregulation of METTL3 attenuated I/R and H/R-induced cell apoptosis. In addition, we screened out that two miRNAs, including miR-25-3p and miR-873-5p, were positively regulated by METTL3 in cardiomyocytes in a DGCR8-dependent manner. In addition, both miR-25-3p and miR-873-5p were significantly downregulated by I/R and H/R treatments in mice tissues and cardiomyocytes, and overexpression of the above two miRNAs were effective to improve cell viability in cardiomyocytes under H/R stress. Next, we evidenced that METTL3 suppressed H/R-induced cell death via upregulating miR-25-3p and miR-873-5p. Finally, the potential downstream mechanisms were investigated, and we expectedly found that METTL3 activated the PI3K/Akt pathway in H/R-treated cardiomyocytes through modulating miR-25-3p and miR-873-5p, and the PI3K/Akt pathway inhibitor (LY294002) abrogated the protective effects of METTL3 overexpression in cardiomyocytes with H/R treatment. Collectively, we concluded that METTL3 upregulated miR-25-3p and miR-873-5p to activate the PI3K/Akt pathway, resulting in the suppression of I/R injury.
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Affiliation(s)
- Xiangmei Zhao
- Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Lei Yang
- Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
| | - Lijie Qin
- Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan, China
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22
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Song Y, Liu W, Zhao Y, Zang J, Gao H. Ochratoxin A induces human kidney tubular epithelial cell apoptosis through regulating lipid raft/PTEN/AKT signaling pathway. ENVIRONMENTAL TOXICOLOGY 2021; 36:1880-1885. [PMID: 34101318 DOI: 10.1002/tox.23308] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 05/26/2021] [Accepted: 05/30/2021] [Indexed: 06/12/2023]
Abstract
Ochratoxin A (OTA) is a fungal toxin that causes serious threat to human health. OTA could lead to the injury of various tissues, especially kidney injury. However, the toxic effects of OTA on human kidney tubular epithelial cell (HK-2) and the possible mechanism remains poorly understood. This study was to investigate the toxic effects of OTA on HK-2 and elucidate the molecular mechanism. HK-2 cells were treated OTA to evaluate the effect of OTA on cell viability and apoptosis. OTA inhibited the growth of HK-2 in a concentration-dependent manner. With the concentration increased, OTA significantly lead to the apoptosis of HK-2. OTA could increase the levels of reactive oxygen species (ROS) and Malondialdehyde (MDA). Superoxide dismutase (SOD) and glutathione (GSH) activities were decreased by OTA. Furthermore, OTA increased Caspase-3 and Bax expression and decreased BCL2 expression. Compared to the control group, the expression of PTEN was increased and the expression of PI3K and AKT were decreased in OTA treated groups. In addition, we found OTA could disrupt the formation of lipid raft by attenuating sphingomyelin and cholesterol levels. In conclusion, our results indicated that OTA induces apoptosis in HK-2 through regulating PTEN/AKT signaling pathway via disrupting lipid raft formation.
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Affiliation(s)
- Yanyan Song
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, China
| | - Wei Liu
- Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yao Zhao
- Department of Nephrology, The Second Hospital of Jilin University, Changchun, China
| | - Junting Zang
- Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, China
| | - Hang Gao
- Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, China
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23
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Wang J, Li T, Wang B. Exosomal transfer of miR‑25‑3p promotes the proliferation and temozolomide resistance of glioblastoma cells by targeting FBXW7. Int J Oncol 2021; 59:64. [PMID: 34278448 PMCID: PMC8295027 DOI: 10.3892/ijo.2021.5244] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 06/24/2021] [Indexed: 12/18/2022] Open
Abstract
Intrinsic or acquired resistance to temozolomide (TMZ) is a frequent occurrence in patients with glioblastoma (GBM). Accumulating evidence has indicated that the exosomal transfer of proteins and RNAs may confer TMZ resistance to recipient cells; however, the potential molecular mechanisms are not fully understood. Thus, the aim of the present study was to elucidate the possible role of exosomal microRNAs (miRNAs/miRs) in the acquired resistance to TMZ in GBM. A TMZ-resistant GBM cell line (A172R) was used, and exosomes derived from A172R cells were extracted. Exosomal miR-25-3p was identified as a miRNA associated with TMZ resistance. The potential functions of exosomal miR-25-3p were evaluated by reverse transcription-quantitative PCR, as well as cell viability, colony formation and soft agar assay, flow cytometry, western blot analysis, BrdU incorporation assay, tumor xenograft formation, luciferase reporter assay and RNA immunoprecipitation. It was found that A172R-derived exosomes promoted the proliferation and TMZ resistance of sensitive GBM cells. Moreover, miR-25-3p epxression was upregulated in the exosomes of A172R cells and in serum samples of patients with GBM treated with TMZ. The depletion of exosomal miR-25-3p partially abrogated the effects induced by the transfer of exosomes from A172R cells. By contrast, miR-25-3p overexpression facilitated the proliferation and TMZ resistance of sensitive GBM cells. F-box and WD repeat domain-containing-7 (FBXW7) was identified as a direct target of miR-25-3p. FBXW7 knockdown promoted the proliferation and TMZ resistance of GBM cells. Furthermore, the exosomal transfer of miR-25-3p promoted c-Myc and cyclin E expression by downregulating FBXW7. Our results provided a novel insight into exosomal microRNAs in acquired TMZ resistance of GBM cells. Besides, exosomal miR-25-3p might be a potential prognostic marker for GBM patients.
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Affiliation(s)
- Jianxin Wang
- Department of Neurosurgery, Henan Provincial People's Hospital, Henan Provincial Cerebrovascular Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, P.R. China
| | - Tianxiao Li
- Department of Intervention Therapy, Henan Provincial People's Hospital, Henan Provincial Cerebrovascular Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, P.R. China
| | - Bin Wang
- Department of Neurosurgery, Henan Provincial People's Hospital, Henan Provincial Cerebrovascular Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, P.R. China
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24
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Zhang X, He Y, Gu H, Liu Z, Li B, Yang Y, Hao J, Hua R. Construction of a Nine-MicroRNA-Based Signature to Predict the Overall Survival of Esophageal Cancer Patients. Front Genet 2021; 12:670405. [PMID: 34093662 PMCID: PMC8170160 DOI: 10.3389/fgene.2021.670405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Accepted: 03/22/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Esophageal cancer (EC) is a common malignant tumor. MicroRNAs (miRNAs) play a key role in the occurrence and metastasis and are closely related to the prognosis of EC. Therefore, it will provide a powerful tool to predict the overall survival (OS) of EC patients based on miRNAs expression in EC tissues and blood samples. METHODS Five independent databases, TCGA, GSE106817, GSE113486, GSE122497, and GSE112264, were used to construct nine-miRna signature and nomograms for prognosis. The bioinformatics analysis was used to predict the enrichment pathways of targets. RESULTS A total of 132 overexpressed miRNAs and 23 suppressed miRNAs showed significant differential expression in both EC serum and tissue samples compared with normal samples. We also showed that nine miRNAs were related to the prognosis of EC. Higher levels of miR-15a-5p, miR-92a-3p, miR-92a-1-5p, miR-590-5p, miR-324-5p, miR-25-3p, miR-181b-5p, miR-421, and miR-93-5p were correlated to the shorter survival time in patients with EC. In addition, we constructed a risk prediction model based on the levels of nine differentially expressed miRNAs (DEMs) and found that the OS time of EC patients with high-risk score was shorter than that of EC patients with low-risk score. Furthermore, our results showed that the risk prediction scores of EC samples were higher than those of normal samples. Finally, the area under the curve (AUC) was used to analyze the risk characteristics of EC and normal controls. By calculating the AUC and the calibration curve, the RNA signature showed a good performance. Bioinformatics analysis showed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling. Finally, 14 messenger RNAs (mRNAs) were identified as hub targets of nine miRNAs, including BTRC, SIAH1, RNF138, CDC27, NEDD4L, MKRN1, RLIM, FBXO11, RNF34, MYLIP, FBXW7, RNF4, UBE3C, and RNF111. TCGA dataset validation showed that these hub targets were significantly differently expressed in EC tissues compared with normal samples. CONCLUSION We have constructed maps and nomograms of nine-miRna risk signals associated with EC prognosis. Bioinformatics analysis revealed that nine DEMs were associated with several crucial signaling, including p53, FoxO, PI3K-Akt, HIF-1, and TORC1 signaling, in EC. We think that this study will provide clinicians with an effective decision-making tool.
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Affiliation(s)
- Xiaobin Zhang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
- Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yi He
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Haiyong Gu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Zhichao Liu
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Bin Li
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yang Yang
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jie Hao
- Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Rong Hua
- Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
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25
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Liu Y, Shen H, Yuan ST, Liu QH. Role of microRNA-25 in high glucose cultured Müller glia. Int J Ophthalmol 2021; 14:643-648. [PMID: 34012877 DOI: 10.18240/ijo.2021.05.02] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 02/18/2021] [Indexed: 12/14/2022] Open
Abstract
AIM To investigate the role of microRNA-25 (miR-25) in proliferation and apoptosis of retinal Müller glia (MG) under high glucose condition. METHODS The purity of the cultured cells was verified by immunocytochemistry and flow cytometry using antibodies that specifically recognized MG. The expression level of miR-25 under normal and high glucose conditions were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). miR-25 mimics and negative control were transfected into MG and multiple functional experiments including cell counting kit-8 assay, EDU assay, and flow cytometry were conducted to explore the effects of miR-25 on the proliferation and apoptosis of high glucose cultured MG (HGMG). RESULTS Immunocytochemistry and flow cytometry confirmed the high purity of primary cultured MG. RT-PCR results showed that the expression level of miR-25 was significantly repressed in HGMG, while over-expression of miR-25 by miR-25 mimic markedly inhibited the high glucose induced cell apoptosis and promoted the proliferation of MG. CONCLUSION The expression level of miR-25 is significantly downregulated in HGMG and its overexpression could attenuate the high glucose damages on MG by promoting proliferation and reducing apoptosis.
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Affiliation(s)
- Yu Liu
- Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Han Shen
- Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Song-Tao Yuan
- Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Qing-Huai Liu
- Department of Ophthalmology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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26
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Meng J, Zhang C, Zhao T, Shi G, Zhao J, Lin Z. MicroRNA-210 targets FBXO31 to inhibit tumor progression and regulates the Wnt/β-catenin signaling pathway and EMT in esophageal squamous cell carcinoma. Thorac Cancer 2021; 12:932-940. [PMID: 33538099 PMCID: PMC7952796 DOI: 10.1111/1759-7714.13860] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 12/27/2020] [Accepted: 01/10/2021] [Indexed: 12/30/2022] Open
Abstract
Evidence from previous studies showed that the dysregulation of microRNA (miR) is frequently associated with tumor progression. The aberrant miR‐210 expression has been identified in a variety of tumors. However, its biological roles in esophageal squamous cell carcinoma (ESCC) still need further elucidation. Thus, in the current study we explore the roles of miR‐210 in ESCC progression. The findings of our study reveal that miR‐210 is down‐regulated in ESCC, which indicates poor prognosis and aggressive tumor progression. Moreover, miR‐210 restoration was found to enhance ESCC viability, invasion, and migration abilities. F‐Box only protein 31 (FBXO31) was confirmed to be one of the targets of miR‐210 in ESCC cells. Results also revealed that miR‐210 played crucial roles in regulating ESCC cell epithelial‐mesenchymal transition (EMT) and Wnt/β‐catenin signaling. In conclusion, data show that miR‐210 serves as an anti‐ESCC miR via down‐regulation of FBXO31 and regulation of EMT and Wnt signaling, suggesting that the miR‐210/FBXO31 axis may function as promising therapeutic targets and effective prognostic markers for ESCC patients. miR‐210 serves as an anti‐ESCC miR via down‐regulation of FBXO31 and regulation of EMT and Wnt signaling
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Affiliation(s)
- Jing Meng
- Department of Gastroenterology, Rizhao Hospital of TCM, Rizhao, China
| | - Chao Zhang
- Department of Gastroenterology, Rizhao Hospital of TCM, Rizhao, China
| | - Tongquan Zhao
- Department of General Surgery, People's Hospital of Rizhao, Rizhao, China
| | - Guangwen Shi
- Health Management Center, Zhangqiu District People's Hospital, Jinan, China
| | - Jingjing Zhao
- Department of Surgery, Zhangqiu District People's Hospital, Jinan, China
| | - Zhaoxia Lin
- Department of Clinical Laboratory, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
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27
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Balta E, Kramer J, Samstag Y. Redox Regulation of the Actin Cytoskeleton in Cell Migration and Adhesion: On the Way to a Spatiotemporal View. Front Cell Dev Biol 2021; 8:618261. [PMID: 33585453 PMCID: PMC7875868 DOI: 10.3389/fcell.2020.618261] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/21/2020] [Indexed: 12/12/2022] Open
Abstract
The actin cytoskeleton of eukaryotic cells is a dynamic, fibrous network that is regulated by the concerted action of actin-binding proteins (ABPs). In particular, rapid polarization of cells in response to internal and external stimuli is fundamental to cell migration and invasion. Various isoforms of ABPs in different tissues equip cells with variable degrees of migratory and adhesive capacities. In addition, regulation of ABPs by posttranslational modifications (PTM) is pivotal to the rapid responsiveness of cells. In this context, phosphorylation of ABPs and its functional consequences have been studied extensively. However, the study of reduction/oxidation (redox) modifications of oxidation-sensitive cysteine and methionine residues of actin, ABPs, adhesion molecules, and signaling proteins regulating actin cytoskeletal dynamics has only recently emerged as a field. The relevance of such protein oxidations to cellular physiology and pathophysiology has remained largely elusive. Importantly, studying protein oxidation spatiotemporally can provide novel insights into localized redox regulation of cellular functions. In this review, we focus on the redox regulation of the actin cytoskeleton, its challenges, and recently developed tools to study its physiological and pathophysiological consequences.
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Affiliation(s)
- Emre Balta
- Section Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, Germany
| | - Johanna Kramer
- Section Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, Germany
| | - Yvonne Samstag
- Section Molecular Immunology, Institute of Immunology, Heidelberg University, Heidelberg, Germany
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