miR-181 regulates cisplatin-resistant non-small cell lung cancer via downregulation of autophagy through the PTEN/PI3K/AKT pathway.
miR-181 regulates cisplatin-resistant non-small cell lung cancer via downregulation of autophagy through the PTEN/PI3K/AKT pathway.
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DOI：
10.3892/or.2018.6268
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发表时间：
2018-04
期刊：
影响因子：
4.2
通讯作者：
Rong L
中科院分区：
文献类型：
--
作者：
Liu J;Xing Y;Rong L
已发现许多 miRNA 在多种癌症中异常表达或突变，因此被认为是癌基因或抑癌基因。本研究的目的是探讨 miR-181 对顺铂耐药的非小细胞肺癌 (NSCLC) 的影响。在顺铂耐药的 NSCLC 患者中，miR-181 表达显着降低。此外，在顺铂耐药的人肺腺癌细胞系A549/DDP中，miR-181下调促进细胞生长和转移并抑制细胞凋亡，而miR-181过表达则发挥相反作用。此外，miR-181下调通过抑制PTEN/PI3K/AKT/mTOR通路抑制A549/DDP细胞中LC3和ATG5蛋白表达，而miR-181过表达通过促进PTEN/PI3K/AKT/mTOR信号传导恢复LC3和ATG5蛋白表达。反过来，PTEN 抑制剂通过 PI3K/AKT/mTOR 通路调节自噬，降低 miR-181 过表达对 A549/DDP 细胞生长的抗癌作用。因此，miR-181作为一个已确定的限速miRNA靶标，在细胞凋亡的调节中发挥作用，可能成为顺铂耐药NSCLC的新型且重要的调节因子。
A number of miRNAs have been found to be abnormally expressed or mutated in numerous cancers and thus, are considered to act as oncogenes or tumor suppressor genes. The aim of the present study was to investigate the effect of miR-181 on cisplatin-resistant non-small cell lung cancer (NSCLC). In patients with cisplatin-resistant NSCLC, miR-181 expression was found to be markedly decreased. In addition, in the cisplatin-resistant human lung adenocarcinoma cell line A549/DDP, miR-181 downregulation promoted cell growth and metastasis and inhibited cell apoptosis, whereas miR-181 overexpression exerted the opposite effects. Furthermore, miR-181 downregulation suppressed LC3 and ATG5 protein expression in A549/DDP cells through suppression of the PTEN/PI3K/AKT/mTOR pathway, whereas miR-181 overexpression recovered LC3 and ATG5 protein expression by promoting PTEN/PI3K/AKT/mTOR signaling. In turn, PTEN inhibitors reduced the anticancer effects of miR-181 overexpression on A549/DDP cell growth via the regulation of autophagy through the PI3K/AKT/mTOR pathway. Therefore, miR-181 may be a novel and important regulator of cisplatin-resistant NSCLC by serving a role in the regulation of apoptosis, as an established rate-limiting miRNA target.
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影响因子：
11.2
作者：
Voortman J;Goto A;Mendiboure J;Sohn JJ;Schetter AJ;Saito M;Dunant A;Pham TC;Petrini I;Lee A;Khan MA;Hainaut P;Pignon JP;Brambilla E;Popper HH;Filipits M;Harris CC;Giaccone G
通讯作者：
Giaccone G
影响因子：
3.3
作者：
Yamamoto N;Goto K;Nishio M;Chikamori K;Hida T;Maemondo M;Katakami N;Kozuki T;Yoshioka H;Seto T;Tajima K;Tamura T
通讯作者：
Tamura T
影响因子：
2.4
作者：
Kelley, Michael J.;Jha, Gautam;Ready, Neal
通讯作者：
Ready, Neal
影响因子：
3.8
作者：
Belani CP;Yamamoto N;Bondarenko IM;Poltoratskiy A;Novello S;Tang J;Bycott P;Niethammer AG;Ingrosso A;Kim S;Scagliotti GV
通讯作者：
Scagliotti GV
影响因子：
3.6
作者：
Li, Yi Rong;Li, Shiming;Lin, Chi-Chen
通讯作者：
Lin, Chi-Chen