miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer.
miR‑448 targets Rab2B and is pivotal in the suppression of pancreatic cancer.
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miR-448 靶向 Rab2B，在抑制胰腺癌中发挥关键作用
DOI：
10.3892/or.2018.6562
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发表时间：
2018-09
期刊：
影响因子：
4.2
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Jin J;Wu Y;Zhou D;Sun Q;Wang W
胰腺癌存活率的改善一直缓慢，患者的死亡率继续上升。据报道，MicroRNA (miR)-448在几种类型的癌症中显著下调。在本研究中，Rab2B是miR-488的靶点，通过生物信息学分析得到证实，并通过荧光素酶报告基因试验得到验证。选取浙江大学医学院第一附属医院确诊的胰腺癌患者72例，收集肿瘤标本及其邻近正常组织进行分析。采用逆转录-聚合酶链式反应分析，定量检测miR-448和Rab2B在这些组织和胰腺癌细胞系中的表达水平。通过细胞转染实现miR-448过表达。western blot检测蛋白表达。分别采用CCK-8法和流式细胞术分析细胞活力、细胞周期和细胞凋亡。结果显示，miR-448与Rab2B在胰腺组织和细胞系中呈负相关。生物信息学分析结果表明，miR-448直接靶向Rab2B。PANC-1细胞中异常的miR-448水平下调Rab2B的表达，显著降低细胞增殖，促进癌细胞凋亡。研究还发现，miR-448模拟物导致G0/G1细胞周期阻滞，并影响细胞周期调节因子的表达，包括cyclin D1、p21和p27。此外，miR-448模拟物导致Akt/哺乳动物雷帕霉素信号通路靶点失活。miR-448模拟诱导细胞凋亡，激活caspase-3、caspase-9和聚adp核糖聚合酶的表达。结果表明，miR-448是Rab2B的负调控因子，促进胰腺癌细胞周期阻滞和细胞凋亡。
Improvements in survival rates for pancreatic cancer have been slow and the morality rate continues to increase in patients. MicroRNA (miR)-448 is reported to be significantly downregulated in several types of cancer. In this study, Rab2B is target of miR-488 was confirmed by bioinformatics analysis and validated using a luciferase reporter assay. A total of 72 cases of pancreatic cancer in patients diagnosed at The First Affiliated Hospital, School of Medicine, Zhejiang University (Hangzhou, China) were enrolled, and cancer specimens and their adjacent normal tissues were collected for analysis. The expression levels of miR-448 and Rab2B in these tissues and in pancreatic cancer cell lines were quantified using reverse transcription-polymerase chain reaction analysis. miR-448 overexpression was achieved by cell transfection. Protein expression was assessed using western blot analysis. Cell viability, cell cycle and apoptosis were analyzed using CCK-8 assay and flow cytometry, respectively. The results revealed a negative correlation between miR-448 and Rab2B in the pancreatic tissues and cell lines. The results of bioinformatics analysis indicated that miR-448 directly targeted Rab2B. Aberrant miR-448 levels in PANC-1 cells downregulated the expression of Rab2B, and significantly decreased cell proliferation and promoted apoptosis of cancer cells. It was also found that miR-448 mimics resulted in G0/G1 cell cycle arrest and affected the expression of cell cycle regulators, including cyclin D1, p21 and p27. In addition, the miR-448 mimics led to inactivation of the Akt/Mammalian target of rapamycin signaling pathway. The miR-448 mimics induced apoptosis and activated the expression of caspase-3, caspase-9 and poly(ADP-ribose) polymerase. The results suggested that miR-448 was a negative regulator of Rab2B and promoted cell cycle arrest and apoptosis in pancreatic cancer.
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作者：
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