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1
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Sun Q, Lei X, Yang X. CircRNAs as upstream regulators of miRNA//HMGA2 axis in human cancer. Pharmacol Ther 2024; 263:108711. [PMID: 39222752 DOI: 10.1016/j.pharmthera.2024.108711] [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: 05/22/2024] [Revised: 07/21/2024] [Accepted: 08/30/2024] [Indexed: 09/04/2024]
Abstract
High mobility group protein A2 (HMGA2) is widely recognized as a chromatin-binding protein, whose overexpression is observed in nearly all human cancers. It exerts its oncogenic effects by influencing various cellular processes such as the epithelial-mesenchymal transition, cell differentiation, and DNA damage repair. MicroRNA (miRNA) serves as a pivotal gene expression regulator, concurrently modulating multiple genes implicated in cancer progression, including HMGA2. It also serves as a significant biomarker for cancer. Circular RNA (circRNA) plays a crucial role in gene regulation primarily by sequestering miRNAs and impeding their ability to enhance the expression of other genes, including HMGA2. Increasingly, studies have underscored the vital role of miRNA/HMGA2 interactions in cancer. Given the significance of circRNA as an upstream regulatory mediator and the complexity of regulatory mechanisms, we hereby present a comprehensive overview of the pivotal role of circRNAs as upstream regulators of the miRNA//HMGA2 axis in human cancers. This insight may herald a novel direction for future cancer research.
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Affiliation(s)
- Qiqi Sun
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, China
| | - Xiaoyong Lei
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, China
| | - Xiaoyan Yang
- School of Pharmaceutical Science, Hengyang Medical College, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, China; Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, 28 Western Changsheng Road, Hengyang, Hunan 421001, China.
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2
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Liu B, Liu L, Liu Y. Targeting cell death mechanisms: the potential of autophagy and ferroptosis in hepatocellular carcinoma therapy. Front Immunol 2024; 15:1450487. [PMID: 39315094 PMCID: PMC11416969 DOI: 10.3389/fimmu.2024.1450487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/21/2024] [Indexed: 09/25/2024] Open
Abstract
Ferroptosis is a type of cell death that plays a remarkable role in the growth and advancement of malignancies including hepatocellular carcinoma (HCC). Non-coding RNAs (ncRNAs) have a considerable impact on HCC by functioning as either oncogenes or suppressors. Recent research has demonstrated that non-coding RNAs (ncRNAs) have the ability to control ferroptosis in HCC cells, hence impacting the advancement of tumors and the resistance of these cells to drugs. Autophagy is a mechanism that is conserved throughout evolution and plays a role in maintaining balance in the body under normal settings. Nevertheless, the occurrence of dysregulation of autophagy is evident in the progression of various human disorders, specifically cancer. Autophagy plays dual roles in cancer, potentially influencing both cell survival and cell death. HCC is a prevalent kind of liver cancer, and genetic mutations and changes in molecular pathways might worsen its advancement. The role of autophagy in HCC is a subject of debate, as it has the capacity to both repress and promote tumor growth. Autophagy activation can impact apoptosis, control proliferation and glucose metabolism, and facilitate tumor spread through EMT. Inhibiting autophagy can hinder the growth and spread of HCC and enhance the ability of tumor cells to respond to treatment. Autophagy in HCC is regulated by several signaling pathways, such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs. Utilizing anticancer drugs to target autophagy may have advantageous implications for the efficacy of cancer treatment.
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Affiliation(s)
- Beibei Liu
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ling Liu
- Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yang Liu
- Day Surgery Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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3
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Tang Q, Wu S, Zhao B, Li Z, Zhou Q, Yu Y, Yang X, Wang R, Wang X, Wu W, Wang S. Reprogramming of glucose metabolism: The hallmark of malignant transformation and target for advanced diagnostics and treatments. Biomed Pharmacother 2024; 178:117257. [PMID: 39137648 DOI: 10.1016/j.biopha.2024.117257] [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: 06/11/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 08/15/2024] Open
Abstract
Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the "Warburg effect". The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers.
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Affiliation(s)
- Qing Tang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China.
| | - Siqi Wu
- The First Clinical School of Guangzhou University of Chinese Medicine；Department of Oncology, the First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510000, China; Zhongshan Institute for Drug Discovery, SIMM, CAS, Zhongshan 528400, China
| | - Baiming Zhao
- The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Department of Traditional Chinese Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Zhanyang Li
- School of Biosciences and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Qichun Zhou
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Yaya Yu
- The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Xiaobing Yang
- The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Rui Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Xi Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China
| | - Wanyin Wu
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China.
| | - Sumei Wang
- State Key Laboratory of Traditional Chinese Medicine Syndrome, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, Guangdong Provincial Hospital of Chinese Medicine; State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; The Second Clinical Medical College, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, Guangdong, 510120, P. R. China; Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510120, P. R. China.
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Dawoud A, Elmasri RA, Mohamed AH, Mahmoud A, Rostom MM, Youness RA. Involvement of CircRNAs in regulating The "New Generation of Cancer Hallmarks": A Special Depiction on Hepatocellular Carcinoma. Crit Rev Oncol Hematol 2024; 196:104312. [PMID: 38428701 DOI: 10.1016/j.critrevonc.2024.104312] [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: 10/06/2023] [Revised: 02/01/2024] [Accepted: 02/26/2024] [Indexed: 03/03/2024] Open
Abstract
The concept of 'Hallmarks of Cancer' is an approach of reducing the enormous complexity of cancer to a set of guiding principles. As the underlying mechanism of cancer are portrayed, we find that we gain insight and additional aspects of the disease arise. The understanding of the tumor microenvironment (TME) brought a new dimension and led to the discovery of novel hallmarks such as senescent cells, non-mutational epigenetic reprogramming, polymorphic microbiomes and unlocked phenotypic plasticity. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across all species. Recent studies on the circRNAs have highlighted their crucial function in regulating the formation of human malignancies through a range of biological processes. The primary goal of this review is to clarify the role of circRNAs in the most common form of liver cancer, hepatocellular carcinoma (HCC). This review also addressed the topic of how circRNAs affect HCC hallmarks, including the new generation hallmarks. Finally, the enormous applications that these rapidly expanding ncRNA molecules serve in the functional and molecular development of effective HCC diagnostic biomarkers and therapeutic targets.
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Affiliation(s)
- A Dawoud
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, New Administrative Capital, Egypt; School of Medicine, University of North California, Chapel Hill, NC 27599, USA
| | - R A Elmasri
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, New Administrative Capital, Egypt
| | - A H Mohamed
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, New Administrative Capital, Egypt; Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt
| | - A Mahmoud
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, New Administrative Capital, Egypt; Biotechnology School, Nile University, Giza 12677, Egypt
| | - M M Rostom
- Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo 11835, Egypt
| | - R A Youness
- Molecular Genetics and Biochemistry Department, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), 11835, New Administrative Capital, Egypt.
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Zhang L, He S, Guan H, Zhao Y, Zhang D. Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis. Hepatobiliary Pancreat Dis Int 2024; 23:52-63. [PMID: 37516591 DOI: 10.1016/j.hbpd.2023.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 07/10/2023] [Indexed: 07/31/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is the fourth leading cause of cancer-related deaths worldwide. Previous evidence shows that the expression of circulating RNA ZFR (circZFR) is upregulated in HCC tissues. However, the molecular mechanism of circZFR in HCC is unclear. METHODS Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was employed to detect the expression of circZFR, microRNA-624-3p (miR-624-3p) and WEE1 in HCC tissues and cells. RNase R assay and actinomycin D treatment assay were used to analyze the characteristics of circZFR. For functional analysis, the capacities of colony formation, cell proliferation, cell apoptosis, migration and invasion were assessed by colony formation assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry assay and transwell assay. Western blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition (EMT)-related proteins. The interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft models were established to determine the role of circZFR in vivo. RESULTS circZFR and WEE1 were upregulated, while miR-624-3p expression was reduced in HCC tissues and cells. circZFR could sponge miR-624-3p, and WEE1 was a downstream gene of miR-624-3p. Knockdown of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR-624-3p inhibitor restored this change. Overexpression of WEE1 abolished the inhibitory effect of miR-624-3p mimic on HCC cells. Mechanistically, circZFR acted as a competitive endogenous RNA (ceRNA) to regulate WEE1 expression by targeting miR-624-3p. Furthermore, in vivo studies have illustrated that circZFR knockdown inhibited tumor growth. CONCLUSIONS circZFR knockdown reduced HCC cell proliferation, migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis, suggesting that the circZFR/miR-624-3p/WEE1 axis might be a potential target for HCC treatment.
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Affiliation(s)
- Li Zhang
- Department of General Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Sai He
- Department of Breast Cancer, Shaanxi Provincial Cancer Hospital, Xi'an 710000, China
| | - Hao Guan
- Department of General Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Yao Zhao
- Department of General Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Di Zhang
- Department of General Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
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6
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Feng Y, Xia S, Hui J, Xu Y. Circular RNA circBNC2 facilitates glycolysis and stemness of hepatocellular carcinoma through the miR-217/high mobility group AT-hook 2 (HMGA2) axis. Heliyon 2023; 9:e17120. [PMID: 37360090 PMCID: PMC10285170 DOI: 10.1016/j.heliyon.2023.e17120] [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: 03/14/2023] [Revised: 06/01/2023] [Accepted: 06/07/2023] [Indexed: 06/28/2023] Open
Abstract
Hepatocellular cancer (HCC) accounts for approximately 90% of primary liver carcinoma and is a significant health threat worldwide. Circular RNA basonuclin 2 (circBNC2) is implicated with the progression of several cancers. However, its roles in carcinogenesis and glycolysis are still unclear in HCC. In this study, the levels of circBNC2 and high mobility group AT-hook 2 (HMGA2) were highly expressed, while these of miR-217 were poorly expressed in HCC tissues and cells. Upregulation of circBNC2 was related to poor prognosis and tumor node metastasis (TNM) stage. Knockdown of circBNC2 inhibited the HCC progression. Moreover, knockdown of circBNC2 suppressed the levels of Ras, ERK1/2, PCNA, HK2, and OCT4. Notably, circBNC2 functioned as a molecular sponge of microRNA 217 (miR-217) to upregulate the HMGA2 expression. The inhibitory effects of the circBNC2 silence on the growth and stemness of HCC cells, and levels of PCNA, HK2 and OCT4 were aggravated by the miR-217 overexpression, but neutralized by the HMGA2 overexpression. Besides, silencing of circBNC2 blocked the tumor growth through upregulating the expression of miR-217 and downregulating the levels of HMGA2, PCNA2, HK2 and OCT4 in vivo. Thus, the current data confirmed that circBNC2 sponged miR-217 to upregulate the HMGA2 level, thereby contributing to the HCC glycolysis and progression. These findings might present novel insight into the pathogenesis and treatment of HCC.
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Affiliation(s)
- Yan Feng
- Department of Integrated, Chongqing University Cancer Hospital & Chongqing Cancer Hospital, Chongqing, 400030, China
| | - Shufeng Xia
- Department of Integrated, Chongqing University Cancer Hospital & Chongqing Cancer Hospital, Chongqing, 400030, China
| | - Junlan Hui
- Department of Radiology, The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College, Chongqing, 400030, China
| | - Yan Xu
- Department of Integrated, Chongqing University Cancer Hospital & Chongqing Cancer Hospital, Chongqing, 400030, China
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Hashemi M, Rashidi M, Hushmandi K, Ten Hagen TLM, Salimimoghadam S, Taheriazam A, Entezari M, Falahati M. HMGA2 regulation by miRNAs in cancer: affecting cancer hallmarks and therapy response. Pharmacol Res 2023; 190:106732. [PMID: 36931542 DOI: 10.1016/j.phrs.2023.106732] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 03/13/2023] [Accepted: 03/14/2023] [Indexed: 03/17/2023]
Abstract
High mobility group A 2 (HMGA2) is a protein that modulates the structure of chromatin in the nucleus. Importantly, aberrant expression of HMGA2 occurs during carcinogenesis, and this protein is an upstream mediator of cancer hallmarks including evasion of apoptosis, proliferation, invasion, metastasis, and therapy resistance. HMGA2 targets critical signaling pathways such as Wnt/β-catenin and mTOR in cancer cells. Therefore, suppression of HMGA2 function notably decreases cancer progression and improves outcome in patients. As HMGA2 is mainly oncogenic, targeting expression by non-coding RNAs (ncRNAs) is crucial to take into consideration since it affects HMGA2 function. MicroRNAs (miRNAs) belong to ncRNAs and are master regulators of vital cell processes, which affect all aspects of cancer hallmarks. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs), other members of ncRNAs, are upstream mediators of miRNAs. The current review intends to discuss the importance of the miRNA/HMGA2 axis in modulation of various types of cancer, and mentions lncRNAs and circRNAs, which regulate this axis as upstream mediators. Finally, we discuss the effect of miRNAs and HMGA2 interactions on the response of cancer cells to therapy. Regarding the critical role of HMGA2 in regulation of critical signaling pathways in cancer cells, and considering the confirmed interaction between HMGA2 and one of the master regulators of cancer, miRNAs, targeting miRNA/HMGA2 axis in cancer therapy is promising and this could be the subject of future clinical trial experiments.
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Affiliation(s)
- 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.
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, 4815733971, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, 4815733971, Iran.
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Timo L M Ten Hagen
- Precision Medicine in Oncology (PrMiO), Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, 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.
| | - Maliheh Entezari
- 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.
| | - Mojtaba Falahati
- Precision Medicine in Oncology (PrMiO), Department of Pathology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.
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Wang J, Zheng L, Hu C, Kong D, Zhou Z, Wu B, Wu S, Fei F, Shen Y. CircZFR promotes pancreatic cancer progression through a novel circRNA-miRNA-mRNA pathway and stabilizing epithelial-mesenchymal transition protein. Cell Signal 2023; 107:110661. [PMID: 36990335 DOI: 10.1016/j.cellsig.2023.110661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 03/09/2023] [Accepted: 03/24/2023] [Indexed: 03/29/2023]
Abstract
Pancreatic cancer (PC) ranks third in incidence and seventh in mortality among cancers worldwide. CircZFR has been implicated in various human cancers. Yet, how they affect PC progression is understudied. Herein, we demonstrated that circZFR was upregulated in PC tissues and cells, a feature that was correlated with the poor performance of patients with PC. Functional analyses elucidated that circZFR facilitated cell proliferation and enhanced tumorigenicity of PC. Moreover, we found that circZFR facilitated cell metastasis by differentially regulating the levels of proteins related to epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that circZFR sponged miR-375, thereby upregulating the downstream target gene, GREMLIN2 (GREM2). Additionally, circZFR knockdown resulted in attenuation of the JNK pathway, an effect that was reversed by GREM2 overexpression. Collectively, our findings implicate circZFR as a positive regulator of PC progression through the miR-375/GREM2/JNK axis.
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Affiliation(s)
- Jing Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Liping Zheng
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Chundong Hu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Demiao Kong
- Department of Thoracic Surgery, Guizhou Provincial People's Hospital, No. 83 EastZhongshan Road, Nanming District, Guiyang, Guizhou 550001, China
| | - Zhongcheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Bin Wu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Shaohan Wu
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China
| | - Famin Fei
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China.
| | - Yiyu Shen
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Jiaxing University, No. 1518, Huancheng North Road, Jiaxing 314000, Zhejiang, China.
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9
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Hashemi M, Nadafzadeh N, Imani MH, Rajabi R, Ziaolhagh S, Bayanzadeh SD, Norouzi R, Rafiei R, Koohpar ZK, Raei B, Zandieh MA, Salimimoghadam S, Entezari M, Taheriazam A, Alexiou A, Papadakis M, Tan SC. Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches. Cell Commun Signal 2023; 21:32. [PMID: 36759819 PMCID: PMC9912665 DOI: 10.1186/s12964-023-01053-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 01/15/2023] [Indexed: 02/11/2023] Open
Abstract
Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Video Abstract.
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Affiliation(s)
- Mehrdad Hashemi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Niloufar Nadafzadeh
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Hassan Imani
- Department of Clinical Science, Faculty of Veterinary Medicine, Shahr-E Kord Branch, Islamic Azad University, Tehran, Chaharmahal and Bakhtiari, Iran
| | - Romina Rajabi
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Setayesh Ziaolhagh
- Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Raheleh Norouzi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Reihaneh Rafiei
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Zeinab Khazaei Koohpar
- Department of Cell and Molecular Biology, Faculty of Biological Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - Behnaz Raei
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
| | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, 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.
| | - Athanasios Alexiou
- Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, Australia
- AFNP Med Austria, Vienna, Austria
| | - Marios Papadakis
- Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany.
| | - Shing Cheng Tan
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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10
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Liu Z, Zhang W, Tu C, Li W, Qi L, Zhang Z, Wan L, Yang Z, Ren X, Li Z. Prognostic and clinicopathologic significance of circZFR in multiple human cancers. World J Surg Oncol 2022; 20:268. [PMID: 36008845 PMCID: PMC9413939 DOI: 10.1186/s12957-022-02733-9] [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: 03/22/2022] [Accepted: 08/17/2022] [Indexed: 11/24/2022] Open
Abstract
Background Abnormally expressed in diverse cancers, circZFR has been correlated with clinical outcomes of cancer patients. Aim of this meta-analysis was to elucidate the prognostic role of circZFR in multiple human malignancies. Methods Literature retrieval was conducted by systematically searching on Pubmed, Web of Science, and the Cochrane Library up to December 2nd, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). The reliability of the pooled results was assessed through sensitivity analysis and the publication bias was measured by Begg’s and Egger’s test. Results A total of seventeen studies comprising 1098 Chinese patients were enrolled in this meta-analysis. Results demonstrated that high circZFR expression was correlated with an unfavorable OS (HR = 2.14, 95% CI 1.74, 2.64). High circZFR expression predicted larger tumor size (OR = 2.79, 95% CI 1.52, 5.12), advanced clinical stage (OR = 3.38, 95% CI 1.49, 7.65), tendentiousness of lymph node metastasis (LNM) (OR = 3.08, 95% CI 2.01, 4.71), and malignant grade (OR = 3.18, 95% CI 1.09, 9.30), but not related to age, gender, and distant metastasis (DM). Conclusions High circZFR expression was associated with unfavorable OS and clinicopathologic parameters including tumor size, clinical stage, LNM, and histology grade, implicating a promising prognostic factor in cancers. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02733-9.
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Affiliation(s)
- Zhongyue Liu
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Wenchao Zhang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Chao Tu
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Wenyi Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Lin Qi
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Zhiming Zhang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Lu Wan
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Zhimin Yang
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China
| | - Xiaolei Ren
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China. .,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.
| | - Zhihong Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China. .,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China.
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11
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Matuszyk J. MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy. Mol Med 2022; 28:89. [PMID: 35922756 PMCID: PMC9351108 DOI: 10.1186/s10020-022-00516-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/22/2022] [Indexed: 12/12/2022] Open
Abstract
Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.
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Affiliation(s)
- Janusz Matuszyk
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R. Weigla Street, 53-114, Wroclaw, Poland.
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12
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Abstract
The tumor microenvironment (TME) is a well-recognized system that plays an essential role in tumor initiation, development, and progression. Intense intercellular communication between tumor cells and other cells (especially macrophages) occurs in the TME and is mediated by cell-to-cell contact and/or soluble messengers. Emerging evidence indicates that noncoding RNAs (ncRNAs) are critical regulators of the relationship between cells within the TME. In this review, we provide an update on the regulation of ncRNAs (primarily micro RNAs [miRNAs], long ncRNAs [lncRNAs], and circular RNAs [circRNAs]) in the crosstalk between macrophages and tumor cells in hepatocellular carcinoma (HCC). These ncRNAs are derived from macrophages or tumor cells and act as oncogenes or tumor suppressors, contributing to tumor progression not only by regulating the physiological and pathological processes of tumor cells but also by controlling macrophage infiltration, activation, polarization, and function. Herein, we also explore the options available for clinical therapeutic strategies targeting crosstalk-related ncRNAs to treat HCC. A better understanding of the relationship between macrophages and tumor cells mediated by ncRNAs will uncover new diagnostic biomarkers and pharmacological targets in cancer.
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13
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Niu ZS, Wang WH. Circular RNAs in hepatocellular carcinoma: Recent advances. World J Gastrointest Oncol 2022; 14:1067-1085. [PMID: 35949213 PMCID: PMC9244981 DOI: 10.4251/wjgo.v14.i6.1067] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/22/2021] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Circular RNAs (circRNAs) have covalently closed loop structures at both ends, exhibiting characteristics dissimilar to those of linear RNAs. Emerging evidence suggests that aberrantly expressed circRNAs play crucial roles in hepatocellular carcinoma (HCC) by affecting the proliferation, apoptosis and invasive capacity of HCC cells. Certain circRNAs may be used as biomarkers to diagnose and predict the prognosis of HCC. Therefore, circRNAs are expected to become novel biomarkers and therapeutic targets for HCC. Herein, we briefly review the characteristics and biological functions of circRNAs, focusing on their roles in HCC to provide new insights for the early diagnosis and targeted therapy of HCC.
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Affiliation(s)
- Zhao-Shan Niu
- Laboratory of Micromorphology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
| | - Wen-Hong Wang
- Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong Province, China
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14
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Liu L, Wang H, Yu S, Gao X, Liu G, Sun D, Jiang X. An Update on the Roles of circRNA-ZFR in Human Malignant Tumors. Front Cell Dev Biol 2022; 9:806181. [PMID: 35186956 PMCID: PMC8848330 DOI: 10.3389/fcell.2021.806181] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Accepted: 12/16/2021] [Indexed: 01/11/2023] Open
Abstract
CircRNAs (circular RNAs) are single-stranded RNAs that form covalently closed loops and function as important regulatory elements of the genome through multiple mechanisms. Increasing evidence had indicated that circRNAs, which might serve as either oncogenes or tumor suppressors, played vital roles in the pathophysiology of human diseases, especially in tumorigenesis and progression. CircRNA-ZFR (circular RNA zinc finger RNA binding protein) is a circular RNA that had attracted much attention in recent years. It has been found that circRNA-ZFR was abnormally expressed in a variety of malignant tumors, and its dysregulated expression was closely related to tumor stage, cancer metastasis and patients’ prognosis. Recent studies had shown that aberrantly expressed circRNA-ZFR could regulate the malignant biological behaviors of tumors through various mechanisms; further exploration of circRNA-ZFR expression in tumors and its regulation on malignant biological behaviors such as tumor proliferation, invasion and drug resistance will provide new ideas for clinical tumors diagnosis and treatment.
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15
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MicroRNA-375: potential cancer suppressor and therapeutic drug. Biosci Rep 2021; 41:229736. [PMID: 34494089 PMCID: PMC8458691 DOI: 10.1042/bsr20211494] [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: 06/23/2021] [Revised: 08/31/2021] [Accepted: 09/06/2021] [Indexed: 02/06/2023] Open
Abstract
MiR-375 is a conserved noncoding RNA that is known to be involved in tumor cell proliferation, migration, and drug resistance. Previous studies have shown that miR-375 affects the epithelial-mesenchymal transition (EMT) of human tumor cells via some key transcription factors, such as Yes-associated protein 1 (YAP1), Specificity protein 1 (SP1) and signaling pathways (Wnt signaling pathway, nuclear factor κB (NF-κB) pathway and transforming growth factor β (TGF-β) signaling pathway) and is vital for the development of cancer. Additionally, recent studies have identified microRNA (miRNA) delivery system carriers for improved in vivo transportation of miR-375 to specific sites. Here, we discussed the role of miR-375 in different types of cancers, as well as molecular mechanisms, and analyzed the potential of miR-375 as a molecular biomarker and therapeutic target to improve the efficiency of clinical diagnosis of cancer.
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16
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Liao R, Liu L, Zhou J, Wei X, Huang P. Current Molecular Biology and Therapeutic Strategy Status and Prospects for circRNAs in HBV-Associated Hepatocellular Carcinoma. Front Oncol 2021; 11:697747. [PMID: 34277444 PMCID: PMC8284075 DOI: 10.3389/fonc.2021.697747] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/11/2021] [Indexed: 12/15/2022] Open
Abstract
Circular RNAs (circRNAs) are newly classified noncoding RNA (ncRNA) members with a covalently closed continuous loop structure that are involved in immune responses against hepatitis B virus (HBV) infections and play important biological roles in the occurrence and pathogenesis of HCC progression. The roles of circRNAs in HBV-associated HCC (HBV-HCC) have gained increasing attention. Substantial evidence has revealed that both tissue and circulating circRNAs may serve as potential biomarkers for diagnostic, prognostic and therapeutic purposes. So far, at least four circRNA/miRNA regulatory axes such as circRNA_101764/miR-181, circRNA_100338/miR-141-3p, circ-ARL3/miR-1305, circ-ATP5H/miR-138-5p, and several circulating circRNAs were reported to be associated with HBV-HCC development. Notably, TGF/SMAD, JAK/STAT, Notch and Wnt/β-catenin signaling pathways may play pivotal roles in this HBV-driven HCC via several circRNAs. Moreover, in non-HBV HCC patients or HCC patients partially infected by HBV, numerous circRNAs have been identified to be important regulators impacting the malignant biological behavior of HCC. Furthermore, the role of circRNAs in HCC drug resistance has become a focus of research with the aim of reversing chemoresistance and immune resistance. Herein, we review the molecular biology of circRNAs in HBV-HCC and their potential in therapeutic strategies.
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Affiliation(s)
- Rui Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lei Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jian Zhou
- Department of Hepatobiliary Surgery, The People's Rongchang Hospital, Chongqing, China
| | - Xufu Wei
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ping Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Yun J, Ren J, Liu Y, Dai L, Song L, Ma X, Luo S, Song Y. Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy. Diabetol Metab Syndr 2021; 13:72. [PMID: 34174955 PMCID: PMC8236153 DOI: 10.1186/s13098-021-00692-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 06/14/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Circular RNAs (circRNAs) have been considered as pivotal biomarkers in Diabetic nephropathy (DN). CircRNA ARP2 actin-related protein 2 homolog (circ-ACTR2) could promote the HG-induced cell injury in DN. However, how circ-ACTR2 acts in DN is still unclear. This study aimed to explore the molecular mechanism of circ-ACTR2 in DN progression, intending to provide support for the diagnostic and therapeutic potentials of circ-ACTR2 in DN. METHODS RNA expression analysis was conducted by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell growth was measured via Cell Counting Kit-8 and EdU assays. Inflammatory response was assessed by Enzyme-linked immunosorbent assay. The protein detection was performed via western blot. Oxidative stress was evaluated by the commercial kits. The molecular interaction was affirmed through dual-luciferase reporter and RNA immunoprecipitation assays. RESULTS Circ-ACTR2 level was upregulated in DN samples and high glucose (HG)-treated human renal mesangial cells (HRMCs). Silencing the circ-ACTR2 expression partly abolished the HG-induced cell proliferation, inflammation and extracellular matrix accumulation and oxidative stress in HRMCs. Circ-ACTR2 was confirmed as a sponge for miR-205-5p. Circ-ACTR2 regulated the effects of HG on HRMCs by targeting miR-205-5p. MiR-205-5p directly targeted high-mobility group AT-hook 2 (HMGA2), and HMGA2 downregulation also protected against cell injury in HG-treated HRMCs. HG-mediated cell dysfunction was repressed by miR-205-5p/HMGA2 axis. Moreover, circ-ACTR2 increased the expression of HMGA2 through the sponge effect on miR-205-5p in HG-treated HRMCs. CONCLUSION All data have manifested that circ-ACTR2 contributed to the HG-induced DN progression in HRMCs by the mediation of miR-205-5p/HMGA2 axis.
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Affiliation(s)
- Jie Yun
- Department of Nephrology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Jinyu Ren
- Department of Encephalopathy, Second Hospital Affiliated to Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yufei Liu
- Department of Blood Purification, Second Hospital Affiliated to Heilongjiang University of Chinese Medicine, Harbin, China
| | - Lijuan Dai
- Department of Nephrology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Liqun Song
- Department of Nephrology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xiaopeng Ma
- Department of Nephrology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Shan Luo
- Department of Nephrology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yexu Song
- Department of Science and Technology, Heilongjiang University of Chinese Medicine, No 26, Heping Road, Harbin, 150000, China.
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MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus. BIOLOGY 2021; 10:biology10060534. [PMID: 34203703 PMCID: PMC8232095 DOI: 10.3390/biology10060534] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/08/2021] [Accepted: 06/09/2021] [Indexed: 12/23/2022]
Abstract
Alterations in lipid metabolism within beta cells and islets contributes to dysfunction and apoptosis of beta cells, leading to loss of insulin secretion and the onset of type 2 diabetes. Over the last decade, there has been an explosion of interest in understanding the landscape of gene expression which influences beta cell function, including the importance of small non-coding microRNA sequences in this context. This review sought to identify the microRNA sequences regulated by metabolic challenges in beta cells and islets, their targets, highlight their function and assess their possible relevance as biomarkers of disease progression in diabetic individuals. Predictive analysis was used to explore networks of genes targeted by these microRNA sequences, which may offer new therapeutic strategies to protect beta cell function and delay the onset of type 2 diabetes.
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