miR-144-3p Induces Cell Cycle Arrest and Apoptosis in Pancreatic Cancer Cells by Targeting Proline-Rich Protein 11 Expression via the Mitogen-Activated Protein Kinase Signaling Pathway
miR-144-3p Induces Cell Cycle Arrest and Apoptosis in Pancreatic Cancer Cells by Targeting Proline-Rich Protein 11 Expression via the Mitogen-Activated Protein Kinase Signaling Pathway
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DOI：
10.1089/dna.2017.3656
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发表时间：
2017-08-01
影响因子：
3.1
通讯作者：
Wang, Jianguo
中科院分区：
文献类型：
--
作者：
Li, Jian;Sun, Peisheng;Wang, Jianguo
microRNAs（miRNAs）已被证实参与肿瘤的发生、发展，包括细胞增殖、细胞凋亡和细胞周期阻滞。然而，miR-144- 3 p在胰腺癌（PC）中的潜在作用仍然难以捉摸。在本研究中，我们证明miR-144- 3 p在PC组织和PANC-1细胞中减少，而富含脯氨酸的蛋白11（PRR 11）显著增加。发现miR-144- 3 p模拟物通过将细胞阻滞在细胞周期的S期并诱导PANC-1细胞中的细胞凋亡来抑制细胞增殖。在用miR-144 - 3 p抑制剂处理后，miR-144 - 3 p对细胞增殖和细胞凋亡的影响被逆转。此外，荧光素酶活性测定表明miR-144- 3 p直接靶向PRR 11 3-UTR。此外，用miR-144- 3 p模拟物转染抑制PRR 11的表达。miR-144- 3 p模拟物还上调p-JNK和p-p38的表达，而它们下调p-ERK的表达。miR-144 - 3 p抑制剂可逆转miR-144- 3 p对丝裂原活化蛋白激酶途径蛋白的影响。PRR 11过表达减弱了miR-144- 3 p模拟物对细胞凋亡和细胞周期停滞的影响。增强PRR 11可降低caspase-3的表达。综上所述，我们的研究结果表明miR-1443 p通过靶向PRR 11诱导PC细胞周期阻滞和凋亡。因此，靶向miR-144- 3 p可作为治疗PC的潜在治疗策略。
microRNAs (miRNAs) have been proved to be involved in many events of tumor development and progression, including cell proliferation, cell apoptosis, and cell cycle arrest. However, the potential role of miR-144-3p in pancreatic cancer (PC) remains elusive. In this study, we demonstrated thatmiR-144-3pwas decreased in PC tissues and PANC-1 cells, whereas proline-rich protein 11 (PRR11) was remarkably increased. miR-144-3p mimics were discovered to inhibit cell proliferation by arresting cells at the S-phase of the cell cycle, and inducing cell apoptosis in PANC-1 cells. The effects of miR-144-3p on cell proliferation and cell apoptosis were reversed after treatment with the miR-144-3p inhibitor. Furthermore, a luciferase activity assay indicated that miR-144-3p directly targeted PRR11 3-UTR. Moreover, transfection with miR-144-3p mimics inhibited the expression of PRR11. miR-144-3p mimics also upregulated the expression of p-JNK and p-p38, whereas they downregulated the expression of p-ERK. The effects of miR-144-3p on mitogen-activated protein kinase pathway proteins were reversed by the miR-144-3p inhibitor. PRR11 overexpression attenuated the effect of miR-144-3p mimics on cell apoptosis and cell cycle arrest. The expression of caspase-3was decreased by enhanced PRR11. In summary, our findings indicated thatmiR-1443p induced cell cycle arrest and apoptosis in PC by targeting PRR11. Therefore, the targeting of miR-144-3p could serve as a potential therapeutic strategy for the treatment of PC.