MicroRNA-34家族在恶性肿瘤中的作用：从基础到临床
Role of MicroRNA-34 Family in Malignant Tumors: From Bench to Bedside
DOI: 10.12677/ACM.2023.1361347, PDF,   
作者: 井文君：潍坊医学院临床医学院，山东 潍坊；张 雪, 于晓鹏, 杨 帅, 魏红梅：青岛大学附属青岛市中心医院肿瘤综合二科，山东 青岛
关键词: 恶性肿瘤；MicroRNAs；MiRNA-34；EMT；癌症干细胞；Malignant Tumors； MicroRNAs； MiRNA-34； EMT； Cancer Stem Cells
摘要: 随着分子生物学技术及临床研究的进展，发现恶性肿瘤的发生与发展与许多分子通路相关。MicroRNAs (miRNAs)是一种高度保守的单链内源性非编码RNA，它是多种恶性肿瘤中一类重要的调节因子，可以在翻译水平抑制癌基因的表达，从而抑制恶性肿瘤的产生与发展。miRNAs种类繁多，其中，microRNA-34家族(miRNA-34s)在多种恶性肿瘤的增殖、侵袭、迁移中发挥重要作用。本文将结合最新基础及临床研究，探讨miRNA-34s在乳腺癌、肝细胞癌、非小细胞肺癌、胃癌等多种肿瘤中的表达与作用，以及miRNA-34s对癌症转移相关机制——上皮间质转化(EMT)、癌症干细胞(CSCs)、程序性死亡蛋白-1 (PD-L1)的调节方式，并评估microRNA-34家族作为肿瘤治疗新靶点的潜力。
Abstract: With the progress of molecular biology technology and clinical research, it is found that the occur-rence and development of malignant tumors are related to many molecular pathways. MicroRNAs (miRNAs) is a highly conserved single-stranded endogenous non-coding RNA, which is an important regulator in a variety of malignancies, and can inhibit the expression of oncogenes at the transla-tional level, thus inhibiting the occurrence and development of malignancies. There are many kinds of miRNAs, among which, the microRNA-34 family (miRNA-34s) plays an important role in the pro-liferation, invasion, and migration of a variety of malignant tumors. This paper will combine the latest basic and clinical research to explore the expression and role of miRNA-34s in breast cancer, hepatocellular carcinoma, nonsmall-cell lung cancer, gastric cancer and other cancer, and miR-NA-34s to cancer metastasis related mechanism—epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), programmed cell death 1 ligand 1 (PD-L1) regulation, and evaluate the potential of microRNA-34 family as a new target in tumor treatment.
文章引用：井文君, 张雪, 于晓鹏, 杨帅, 魏红梅. MicroRNA-34家族在恶性肿瘤中的作用：从基础到临床[J]. 临床医学进展, 2023, 13(6): 9624-9633. https://doi.org/10.12677/ACM.2023.1361347

参考文献

[1] WHO. China Globocan, 2020.
https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf
[2] WHO. Globocan, 2020.
https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf
[3] Liu, R., Zhang, C., Hu, Z., et al. (2011) A Five-microRNA Signature Identified from Genome-Wide Serum microRNA Expression Profiling Serves as a Fingerprint for Gastric Cancer Diagnosis. European Journal of Cancer, 47, 784-791. [Google Scholar] [CrossRef] [PubMed]
[4] Liu, G., Jiang, C., Li, D., et al. (2014) MiRNA-34a Inhibits EGFR-Signaling-Dependent MMP7 Activation in Gastric Cancer. Tumor Biology, 35, 9801-9806. [Google Scholar] [CrossRef] [PubMed]
[5] Bonetti, P., Climent, M., Panebianco, F., et al. (2019) Dual Role for miR-34a in the Control of Early Progenitor Proliferation and Commitment in the Mammary Gland and in Breast Can-cer. Oncogene, 38, 360-374. [Google Scholar] [CrossRef] [PubMed]
[6] Shen, Z., Zhan, G., Ye, D., et al. (2012) MicroRNA-34a Affects the Occurrence of Laryngeal Squamous Cell Carcinoma by Targeting the Antiapoptotic Gene Survivin. Medical Oncology, 29, 2473-2480. [Google Scholar] [CrossRef] [PubMed]
[7] Ji, Q., Hao, X., Meng, Y., et al. (2008) Restoration of Tumor Suppressor miRNA-34 Inhibits Human p53-Mutant Gastric Cancer Tumorspheres. BMC Cancer, 8, Article No. 266. [Google Scholar] [CrossRef] [PubMed]
[8] Kim, C.H., Kim, H.K., Rettig, R.L., et al. (2011) miRNA Signature Associated with Outcome of Gastric Cancer Patients Following Chemotherapy. BMC Medical Genomics, 4, Article No. 79. [Google Scholar] [CrossRef] [PubMed]
[9] Bartel, D.P. (2004) MicroRNAs: Genomics, Biogenesis, Mecha-nism, and Function. Cell, 116, 281-297. [Google Scholar] [CrossRef] 
[10] He, L. and Hannon, G.J. (2004) MicroRNAs: Small RNAs with a Big Role in Gene Regulation. Nature Reviews Genetics, 5, 522-531. [Google Scholar] [CrossRef] [PubMed]
[11] Miska, E.A. (2005) How microRNAs Control Cell Division, Differentiation and Death. Current Opinion in Genetics & Development, 15, 563-568. [Google Scholar] [CrossRef] [PubMed]
[12] Bartel, D.P. (2009) MicroRNAs: Target Recognition and Regulato-ry Functions. Cell, 136, 215-233. [Google Scholar] [CrossRef] [PubMed]
[13] Pasquinelli, A.E. (2012) MicroRNAs and Their Targets: Recogni-tion, Regulation and an Emerging Reciprocal Relationship. Nature Reviews Genetics, 13, 271-282. [Google Scholar] [CrossRef] [PubMed]
[14] Zhang, L., Liao, Y. and Tang, L. (2019) MicroRNA-34 Family: A Potential Tumor Suppressor and Therapeutic Candidate in Cancer. Journal of Experimental & Clinical Cancer Research, 38, Arti-cle No. 53. [Google Scholar] [CrossRef] [PubMed]
[15] Hayes, J., Peruzzi, P.P. and Lawler, S. (2014) MicroRNAs in Cancer: Biomarkers, Functions and Therapy. Trends in Molecular Medicine, 20, 460-469. [Google Scholar] [CrossRef] [PubMed]
[16] Kasinski, A.L. and Slack, F.J. (2012) miRNA-34 Prevents Cancer Initiation and Progression in a Therapeutically Resistant K-ras and p53-Induced Mouse Model of Lung Adeno-carcinoma. Cancer Research, 72, 5576-5587. [Google Scholar] [CrossRef] 
[17] Jafari, N. and Abediankenari, S. (2017) MicroRNA-34 Dysregulation in Gastric Cancer and Gastric Cancer Stem Cell. Tumor Biology, 39. [Google Scholar] [CrossRef] [PubMed]
[18] Xiong, S., Hu, M., Li, C., Zhou, X. and Chen, H. (2019) Role of miR-34 in Gastric Cancer: From Bench to Bedside (Review). Oncology Reports, 42, 1635-1646. [Google Scholar] [CrossRef] [PubMed]
[19] Rokavec, M., Li, H., Jiang, L. and Hermeking, H. (2014) The p53/miRNA-34 Axis in Development and Disease. Journal of Molecular Cell Biology, 6, 214-230. [Google Scholar] [CrossRef] [PubMed]
[20] Salzman, D.W., Nakamura, K., Nallur, S., et al. (2016) miRNA-34 Ac-tivity Is Modulated through 5’-End Phosphorylation in Response to DNA Damage. Nature Communications, 7, Article No. 10954. [Google Scholar] [CrossRef] [PubMed]
[21] Sun, H., Tian, J., Xian, W., Xie, T. and Yang, X. (2015) miRNA-34a Inhibits Proliferation and Invasion of Bladder Cancer Cells by Targeting Orphan Nuclear Receptor HNF4G. Disease Markers, 2015, Article ID: 879254. [Google Scholar] [CrossRef] [PubMed]
[22] Kaller, M. and Hermeking, H. (2016) Interplay between Transcription Factors and MicroRNAs Regulating Epithelial-Mesenchymal Transitions in Colorectal Cancer. Advances in Experimental Medicine and Biology, 937, 71-92. [Google Scholar] [CrossRef] [PubMed]
[23] Wang, L., Yu, J., Xu, J., Zheng, C., Li, X. and Du, J. (2015) The Analysis of microRNA-34 Family Expression in Human Cancer Studies Comparing Cancer Tissues with Corre-sponding Pericarcinous Tissues. Gene, 554, 1-8. [Google Scholar] [CrossRef] [PubMed]
[24] Brzozowa, M., Mielańczyk, L., Michalski, M., et al. (2013) Role of Notch Signaling Pathway in Gastric Cancer Pathogenesis. Contemporary Oncology (Pozn), 17, 1-5. [Google Scholar] [CrossRef] [PubMed]
[25] Li, S., Wei, X., He, J., et al. (2021) The Comprehensive Landscape of miR-34a in Cancer Research. Cancer and Metastasis Reviews, 40, 925-948. [Google Scholar] [CrossRef] [PubMed]
[26] Zeng, Z., Chen, X., Zhu, D., Luo, Z. and Yang, M. (2017) Low Expression of Circulating MicroRNA-34c Is Associated with Poor Prognosis in Triple-Negative Breast Cancer. Yonsei Medical Journal, 58, 697-702. [Google Scholar] [CrossRef] [PubMed]
[27] Yang, S., Li, Y., Gao, J., et al. (2013) MicroRNA-34 Suppresses Breast Cancer Invasion and Metastasis by Directly Targeting Fra-1. Oncogene, 32, 4294-4303. [Google Scholar] [CrossRef] [PubMed]
[28] Park, E.Y., Chang, E., Lee, E.J., et al. (2014) Targeting of miR34a-NOTCH1 Axis Reduced Breast Cancer Stemness and Chemoresistance. Cancer Research, 74, 7573-7582. [Google Scholar] [CrossRef] 
[29] Li, Y.L., Liu, X.M., Zhang, C.Y., et al. (2017) Mi-croRNA-34a/EGFR Axis Plays Pivotal Roles in Lung Tumorigenesis. Oncogenesis, 6, e372. [Google Scholar] [CrossRef] [PubMed]
[30] Zhao, K., Cheng, J., Chen, B., Liu, Q., Xu, D. and Zhang, Y. (2017) Circulating microRNA-34 Family Low Expression Correlates with Poor Prognosis in Patients with Non-Small Cell Lung Cancer. Journal of Thoracic Disease, 9, 3735-3746. [Google Scholar] [CrossRef] [PubMed]
[31] Takaishi, S., Okumura, T., Tu, S., et al. (2009) Identification of Gastric Cancer Stem Cells Using the Cell Surface Marker CD44. Stem Cells, 27, 1006-1020. [Google Scholar] [CrossRef] [PubMed]
[32] Shi, L., Wang, Z., Geng, X., Zhang, Y. and Xue, Z. (2020) Exosomal miRNA-34 from Cancer-Associated Fibroblasts Inhibits Growth and Invasion of Gastric Cancer Cells in Vitro and in Vivo. Aging (Albany NY), 12, 8549-8564. [Google Scholar] [CrossRef] [PubMed]
[33] Zhou, Y., Huang, T., Siu, H.L., et al. (2017) IGF2BP3 Functions as a Potential Oncogene and Is a Crucial Target of miR-34a in Gastric Carcinogenesis. Molecular Cancer, 16, Article No. 77. [Google Scholar] [CrossRef] [PubMed]
[34] Zhang, Z., Kong, Y., Yang, W., et al. (2016) Upregulation of mi-croRNA-34a Enhances the DDP Sensitivity of Gastric Cancer Cells by Modulating Proliferation and Apoptosis via Tar-geting MET. Oncology Reports, 36, 2391-2397. [Google Scholar] [CrossRef] [PubMed]
[35] Pu, Y., Zhao, F., Wang, H. and Cai, S. (2017) miRNA-34a-5p Promotes Multi-Chemoresistance of Osteosarcoma through Down-Regulation of the DLL1 Gene. Scientific Reports, 7, Article No. 44218. [Google Scholar] [CrossRef] [PubMed]
[36] Krause, C.J., Popp, O., Thirunarayanan, N., Dittmar, G., Lipp, M. and Müller, G. (2016) MicroRNA-34a Promotes Genomic Instability by a Broad Suppression of Genome Maintenance Mechanisms Downstream of the Oncogene KSHV-vGPCR. Oncotarget, 7, 10414-10432. [Google Scholar] [CrossRef] [PubMed]
[37] Wang, A.M., Huang, T.T., Hsu, K.W., et al. (2014) Yin Yang 1 Is a Target of microRNA-34 Family and Contributes to Gastric Carcinogenesis. Oncotarget, 5, 5002-5016. [Google Scholar] [CrossRef] [PubMed]
[38] Murata, H., Kawano, S., Tsuji, S., et al. (1999) Cyclooxygenase-2 Overexpression Enhances Lymphatic Invasion and Metastasis in Human Gastric Carcinoma. The American Journal of Gastroenterology, 94, 451-455. [Google Scholar] [CrossRef] [PubMed]
[39] Bommer, G.T., Gerin, I., Feng, Y., et al. (2007) p53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes. Current Biology, 17, 1298-1307. [Google Scholar] [CrossRef] [PubMed]
[40] Zhang, D.G., Zheng, J.N. and Pei, D.S. (2014) P53/microRNA-34-Induced Metabolic Regulation: New Opportunities in Anticancer Therapy. Molecular Cancer, 13, Article No. 115. [Google Scholar] [CrossRef] [PubMed]
[41] Yamakuchi, M. and Lowenstein, C.J. (2009) miRNA-34, SIRT1 and p53: The Feedback Loop. Cell Cycle, 8, 712-715. [Google Scholar] [CrossRef] [PubMed]
[42] Yamakuchi, M., Ferlito, M. and Lowenstein, C.J. (2008) miRNA-34a Re-pression of SIRT1 Regulates Apoptosis. Proceedings of the National Academy of Sciences of the United States of Amer-ica, 105, 13421-13426. [Google Scholar] [CrossRef] [PubMed]
[43] Soutto, M., Chen, Z., Bhat, A.A., et al. (2019) Activation of STAT3 Signaling Is Mediated by TFF1 Silencing in Gastric Neoplasia. Nature Communications, 10, Article No. 3039. [Google Scholar] [CrossRef] [PubMed]
[44] Rokavec, M., Öner, M.G., Li, H., et al. (2014) IL-6R/STAT3/miR-34a Feedback Loop Promotes EMT-Mediated Colorectal Cancer Invasion and Metastasis. Journal of Clinical Investigation, 124, 1853-1867. [Google Scholar] [CrossRef] 
[45] Shi, L., Fan, B., Chen, D., et al. (2020) Human Cytomegalovirus Protein UL136 Activates the IL-6/STAT3 Signal through miRNA-138 and miRNA-34c in Gastric Cancer Cells. International Journal of Clinical Oncology, 25, 1936-1944. [Google Scholar] [CrossRef] [PubMed]
[46] Chen, Q.Y., Des Marais, T. and Costa, M. (2019) Deregulation of SATB2 in Carcinogenesis with Emphasis on miRNA-Mediated Control. Carcinogenesis, 40, 393-402. [Google Scholar] [CrossRef] [PubMed]
[47] Lau, W.M., Teng, E., Chong, H.S., et al. (2014) CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells. Cancer Research, 74, 2630-2641. [Google Scholar] [CrossRef] 
[48] Wu, Q., Yang, Z., Wang, F., et al. (2013) miR-NA-19b/20a/92a Regulates the Self-Renewal and Proliferation of Gastric Cancer Stem Cells. Journal of Cell Science, 126, 4220-4229. [Google Scholar] [CrossRef] [PubMed]
[49] 赵丽丽, 赵文文, 冯青青, 赵文飞, 张雪, 井文君, 魏红梅. 沉默PD-L1表达对胃癌细胞生物学行为的影响[J]. 国际肿瘤学杂志, 2021, 48(12): 705-710. [Google Scholar] [CrossRef] 
[50] 郭雅文. PD-L1在乳腺癌患者预后中的诊断价值及miRNA-34a对其调控机制的研究[D]: [博士学位论文]. 武汉: 华中科技大学, 2017.
[51] Cortez, M.A., Ivan, C., Valdecanas, D., et al. (2015) PDL1 Regulation by p53 via miRNA-34. Journal of the National Cancer Institute, 108, djv303. [Google Scholar] [CrossRef] [PubMed]
[52] Hong, D.S., Kang, Y.K., Borad, M., et al. (2020) Phase 1 Study of MRX34, a Liposomal miRNA-34a Mimic, in Patients with Advanced Solid Tumours. British Journal of Cancer, 122, 1630-1637. [Google Scholar] [CrossRef] [PubMed]

为你推荐