MicroRNA-4268 inhibits cell proliferation via AKT/JNK signalling pathways by targeting Rab6B in human gastric cancer
MicroRNA-4268 inhibits cell proliferation via AKT/JNK signalling pathways by targeting Rab6B in human gastric cancer
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MicroRNA-4268 通过靶向 Rab6B 通过 AKT/JNK 信号通路抑制人胃癌中的细胞增殖
DOI：
10.1038/s41417-019-0118-6
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发表时间：
2019-07
影响因子：
6.4
通讯作者：
Tong Dongdong
中科院分区：
文献类型：
--
作者：
Zhao Lingyu;Xue Meng;Zhang Lu;Guo Bo;Qin Yannan;Jiang Qiuyu;Sun Ruifang;Yang Juang;Wang Lumin;Liu Liying;Wang Xiaofei;Huang Chen;Tong Dongdong
MicroRNAs （miRNAs）在胃癌（GC）的发生和发展中起着至关重要的作用。然而，miR-4268在GC中的生物学功能及其机制尚不清楚。在本研究中，qTR-PCR发现miR-4268在GC组织和细胞系中表达明显下调。过表达miR-4268抑制GC细胞增殖和细胞周期G1/S期转变，诱导细胞凋亡。相反，抑制miR-4268促进细胞增殖和G1-S转变，抑制细胞凋亡。进一步分析发现，在GC组织中miR-4268的表达与Rab6B的表达呈负相关。Rab6B被证实是miR-4268的直接靶点。值得注意的是，在GC细胞中，沉默Rab6B与过表达miR-4268诱导的生物学效应相同。重要的是，miR-4268过表达和Rab6B沉默均抑制AKT/JNK信号通路，从而调节细胞周期调节因子（Cyclin D1和CDK4）。相反，抑制miR-4268可促进AKT/JNK信号通路。MiR-4268过表达也促进了p38 MAPK信号通路。综上所述，miR-4268通过靶向Rab6B抑制AKT/JNK信号通路抑制GC细胞增殖，通过促进p38 MAPK信号通路诱导细胞凋亡。我们的研究结果表明miR-4268在胃癌发病机制中的肿瘤抑制作用以及miR-4268在胃癌治疗中的潜力。
MicroRNAs (miRNAs) play critical roles in the tumorigenesis and progression of gastric cancer (GC). However, the biological function of miR-4268 in GC and its mechanism remain unclear. In the present study, qTR-PCR found that the expression of miR-4268 was significantly downregulated in GC tissues and cell lines. The overexpression of miR-4268 inhibited GC cell proliferation and the cell cycle G1/S phase transition, and induced cell apoptosis. In contrast, inhibition of miR-4268 promoted cell proliferation and G1-S transition, and suppressed cell apoptosis. Further analyses revealed that miR-4268 expression was negatively correlated with Rab6B expression in GC tissues. Rab6B was verified to be a direct target of miR-4268. Notably, silencing Rab6B resulted in the same biological effects in GC cells as those induced by overexpression of miR-4268. Importantly, both miR-4268 overexpression and Rab6B silence inhibited the AKT/JNK signaling pathways, which modulated cell cycle regulators (Cyclin D1 and CDK4). In contrast, inhibition of miR-4268 promoted the AKT/JNK signaling pathways. MiR-4268 overexpression also promoted the p38 MAPK signaling pathway. Taken together, miR-4268 suppresses GC cell proliferation through inhibiting the AKT/JNK signaling pathways by targeting Rab6B and induces cell apoptosis through promoting the p38 MAPK signaling pathway. Our findings indicate a tumor-suppressor role of miR-4268 in GC pathogenesis and the potential of miR-4268 in GC theropy.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
4
作者：
F. Opdam;Arnaud Echard;H. Croes;J.A.J.M. van den Hurk;R. A. V. D. Vorstenbosch;L. Ginsel;B. Goud;Jack A.M. Fransen
通讯作者：
F. Opdam;Arnaud Echard;H. Croes;J.A.J.M. van den Hurk;R. A. V. D. Vorstenbosch;L. Ginsel;B. Goud;Jack A.M. Fransen
影响因子：
11.2
作者：
Hou, Qingsong;Wu, Yong Hui;Tan, Patrick
通讯作者：
Tan, Patrick
影响因子：
6.2
作者：
Liu L;Wang Y;Bai R;Yang K;Tian Z
通讯作者：
Tian Z
DOI：
10.1007/978-3-319-11985-4_10
发表时间：
2014
期刊：
--
影响因子：
--
作者：
A. Evangelista;M. Marques
通讯作者：
A. Evangelista;M. Marques