Yong-Ming He, Ai-Jun Ji, Xiao-Yue Xu, Jian-Wei Lu, Chen Yu, Ye Chen
Departments of aIntegrated TCM & Western Medicine bInternal Medicine-Oncology cPain, JiangSu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu Province, China.
Anticancer Drugs. 2017 Nov;28(10):1067-1078. doi: 10.1097/CAD.0000000000000555.
MicroRNAs (miRNAs) have been reported to be associated with cancer progression and carcinogenesis. They are small, highly conserved, noncoding RNA molecules consisting of 19-25 nucleotides. By binding to complementary binding sites within the 3'-untranslated region of target mRNAs, miRNAs inhibit the translation of mRNAs or promote their degradation. miRNAs play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. Similarly, several studies have shown that miRNAs are involved in regulating various biological processes, including apoptosis, proliferation, cellular differentiation, signal transduction, and carcinogenesis. Among miRNAs, one that may be of particular interest in cancer biology is miR-449a, which has been reported to inhibit tumor growth, invasion, and metastasis, and to promote apoptosis and differentiation through the transforming growth factor-β activated kinase 1, NOTCH, nuclear factor-κB/P65/vascular endothelial growth factor, retinoblastoma-E2F, mitogen-activated protein kinase signaling pathways, WNT-β-catenin signaling, tumor protein P53, and androgen receptor signaling pathways. The miR-449 cluster is located in the second intron of CDC20B on chromosome 5q11.2, a region that has been identified as a susceptibility locus in cancer, and the abnormal expression of miR-449a may be related to the occurrence and development of tumors. As one example, miR-449a has been reported to be involved in the development of carcinoma and may be a potential prognostic indicator. On the basis of the putative pathogenetic relationships between cancer and miR-449a, we consider that miR-449a has the potential to serve as a therapeutic agent for the treatment of some types of cancer. In this review, the role of miR-449a in tumorigenesis and its mechanism of action are explored. Furthermore, its potential as a therapeutic agent in cancer treatment is considered.
据报道，微小RNA（miRNA）与癌症进展和致癌作用相关。它们是由19 - 25个核苷酸组成的小型、高度保守的非编码RNA分子。通过与靶mRNA的3'非翻译区内的互补结合位点结合，miRNA抑制mRNA的翻译或促进其降解。miRNA通过作为癌基因或肿瘤抑制因子发挥作用，在癌症的发生和发展中起关键作用。同样，多项研究表明，miRNA参与调节各种生物学过程，包括细胞凋亡、增殖、细胞分化、信号转导和致癌作用。在miRNA中，miR - 449a可能在癌症生物学中特别受关注，据报道它通过转化生长因子-β激活激酶1、NOTCH、核因子-κB/P65/血管内皮生长因子、视网膜母细胞瘤-E2F、丝裂原活化蛋白激酶信号通路、WNT-β-连环蛋白信号通路、肿瘤蛋白P53和雄激素受体信号通路抑制肿瘤生长、侵袭和转移，并促进细胞凋亡和分化。miR - 449簇位于5号染色体q11.2上CDC20B的第二个内含子中，该区域已被确定为癌症的一个易感位点，miR - 449a的异常表达可能与肿瘤的发生和发展有关。例如，据报道miR - 449a参与了癌的发生，可能是一种潜在的预后指标。基于癌症与miR - 449a之间假定的致病关系，我们认为miR - 449a有潜力作为治疗某些类型癌症的治疗剂。在这篇综述中，探讨了miR - 449a在肿瘤发生中的作用及其作用机制。此外，还考虑了其作为癌症治疗治疗剂的潜力。
