Li Tianqi, Pan Hongjie, Li Runsheng
Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai, China.
Tumour Biol. 2016 Sep;37(9):11667-11677. doi: 10.1007/s13277-016-5144-5. Epub 2016 Jul 20.
MicroRNAs (miRNAs) are a group of endogenous, small (about 22 nucleotides) non-coding RNAs which negatively regulate gene expressions. As one of them, miR-204 originates from the sixth intron of the transient receptor potential melastatin 3 (TRPM3) gene. Therefore, expression of miR-204 is under the control of the TRPM3 promoter and regulated by genetic and epigenetic mechanisms. miR-204 has been found to play the important roles in development of eyes and adipogenesis. Its pathological functions have been observed in a few diseases including pulmonary arterial hypertension, diabetes, and various types of cancers. It is believed that miR-204 acts as a tumor-suppressor via promoting apoptosis, conferring the resistance of cancer cells to chemotherapy, and suppressing the self-renewal of cancer stem cells (CSCs) and the epithelial to mesenchymal transition (EMT). Expression of miR-204 is repressed by its targets XRN1 and TRKB in prostate cancer and endometrial carcinoma, respectively; therefore, they establish an oncogenic feedback loops that play an important role promoting development of cancer. In this review, we summarize our current knowledge regarding miR-204, including its expression, regulation and biological functions, especially focusing our discussion on its role in tumor development and tumor progression.
微小RNA(miRNA)是一类内源性的小(约22个核苷酸)非编码RNA,它们负向调节基因表达。作为其中之一,miR-204源自瞬时受体电位香草酸亚家族成员3(TRPM3)基因的第六个内含子。因此,miR-204的表达受TRPM3启动子的控制,并受遗传和表观遗传机制调节。已发现miR-204在眼睛发育和脂肪生成中发挥重要作用。在包括肺动脉高压、糖尿病和各种类型癌症在内的一些疾病中观察到了它的病理功能。据信,miR-204通过促进细胞凋亡、赋予癌细胞对化疗的抗性以及抑制癌症干细胞(CSC)的自我更新和上皮-间质转化(EMT)而发挥肿瘤抑制作用。在前列腺癌和子宫内膜癌中,miR-204的表达分别被其靶标XRN1和酪氨酸激酶受体B(TRKB)抑制;因此,它们建立了致癌反馈环,在促进癌症发展中起重要作用。在这篇综述中,我们总结了目前关于miR-204的知识,包括其表达、调控和生物学功能,尤其着重讨论其在肿瘤发生和肿瘤进展中的作用。