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微小RNA-128通过靶向小鼠双微体4诱导胰腺癌细胞凋亡。

miR-128 induces pancreas cancer cell apoptosis by targeting MDM4.

作者信息

Han Hongchao, Wang Lisheng, Xu Jie, Wang Aikun

机构信息

Department of General Surgery, The Third People's Hospital, Yancheng, Jiangsu 224000, P.R. China.

Department of Gynecology and Obstetrics, The Third People's Hospital, Yancheng, Jiangsu 224000, P.R. China.

出版信息

Exp Ther Med. 2018 Jun;15(6):5017-5022. doi: 10.3892/etm.2018.6047. Epub 2018 Apr 10.

Abstract

MicroRNAs (miRNA/miRs) are small, non-coding RNA molecules (19-25 nucleotides in length), which function to regulate gene expression. It has been reported that miR-128 serves an important role in regulating cancer cell growth; increasing evidence has indicated that the expression of miR-128 is decreased in pancreatic cancer (PC) cells. However, the specific mechanisms of miR-128 in regulating PC cell growth are unclear. In the present study, it was confirmed that the expression of miR-128 was significantly decreased within PC tissues compared with adjacent normal tissues via reverse transcription-quantitative polymerase chain reaction analysis. In addition, miR-128 mimics inhibited PC MIA-PaCa2 cell growth by enhancing cell apoptosis in a caspase-dependent manner. Furthermore, the results of the present study demonstrated that double minute 4 (MDM4) may be a direct target for miR-128 via a dual luciferase report assay; miR-128 may inhibit MDM4 expression, and increase p53 and cleaved caspase-3 protein expression levels. In summary, the present study indicated that miR-128 is downregulated in PC, and it may be a promising target for future PC diagnosis and treatment.

摘要

微小RNA(miRNA/miRs)是一类小的非编码RNA分子(长度为19 - 25个核苷酸),其功能是调节基因表达。据报道,miR - 128在调节癌细胞生长中起重要作用;越来越多的证据表明,胰腺癌(PC)细胞中miR - 128的表达降低。然而,miR - 128调节PC细胞生长的具体机制尚不清楚。在本研究中,通过逆转录 - 定量聚合酶链反应分析证实,与相邻正常组织相比,PC组织中miR - 128的表达显著降低。此外,miR - 128模拟物通过以半胱天冬酶依赖性方式增强细胞凋亡来抑制PC MIA - PaCa2细胞生长。此外,本研究结果表明,双微体4(MDM4)可能是miR - 128的直接靶点,通过双荧光素酶报告基因检测;miR - 128可能抑制MDM4表达,并增加p53和裂解的半胱天冬酶 - 3蛋白表达水平。总之,本研究表明miR - 128在PC中表达下调,它可能是未来PC诊断和治疗的一个有前景的靶点。

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