miRNA-133b 的过度调控通过靶向 EGFR 抑制顺铂诱导的非小细胞肺癌细胞的增殖，该调控作用是通过 PI3K/Akt 和 JAK2/STAT3 信号通路实现的。
Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling pathway by targeting EGFR.
机构信息
Department of Respiratory Medicine, Fourth Hospital of Hebei Medical University, Hebei 050011, P.R. China.
Department of Respiratory Medicine, First Hospital of Shijiazhuang, Hebei 050011, P.R. China.
出版信息
Oncol Rep. 2018 Mar;39(3):1227-1234. doi: 10.3892/or.2018.6215. Epub 2018 Jan 15.
The present study determined the anticancer activity and its mechanism of microRNA‑133b on cell proliferation of cisplatin-induced non-small cell lung cancer cells. The expression of microRNA-133b cisplatin‑induced non-small cell lung cancer (NSCLC) tissue was lower than that of para-carcinoma tissue in patients. Overall survival of higher expression in cisplatin-induced NSCLC patients was higher than that of lower expression in cisplatin‑induced NSCLC patients. Over-regulation of microRNA-133b inhibited cell proliferation and LDH activity, induced apoptosis and caspase-3 activity, suppressed the protein expression of EGFR, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and increased Bax protein expression in cisplatin‑induced A549 cells. EGFR inhibitor (lapatinib) suppressed EGFR protein expression, inhibited cell proliferation and LDH activity, and induced apoptosis and caspase-3 activity in cisplatin-induced A549 cells by over-regulation of microRNA-133b. When EGFR protein expression was suppressed, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and increased Bax protein expression in cisplatin-induced A549 cells by over-regulation of microRNA-133b. Altogether, our results indicated that over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced NSCLC by PI3K/Akt and JAK2/STAT3 signaling pathway by targeting EGFR.
本研究旨在确定 microRNA-133b 对顺铂诱导的非小细胞肺癌细胞增殖的抗癌活性及其作用机制。患者中 microRNA-133b 顺铂诱导的非小细胞肺癌 (NSCLC) 组织的表达低于癌旁组织。顺铂诱导的 NSCLC 患者中高表达者的总生存率高于低表达者。microRNA-133b 的过度调节抑制细胞增殖和 LDH 活性，诱导细胞凋亡和 caspase-3 活性，抑制 EGFR、PI3K、p-Akt、p-JAK2 和 p-STAT3 的蛋白表达，降低 cyclin D1 并增加 Bax 蛋白表达在顺铂诱导的 A549 细胞中。EGFR 抑制剂 (拉帕替尼) 通过 microRNA-133b 的过度调节抑制 EGFR 蛋白表达，抑制细胞增殖和 LDH 活性，并诱导细胞凋亡和 caspase-3 活性在顺铂诱导的 A549 细胞中。当 EGFR 蛋白表达受到抑制时，microRNA-133b 的过度调节降低了 cyclin D1 并增加了 Bax 蛋白表达，从而抑制了顺铂诱导的 A549 细胞中的 PI3K/Akt 和 JAK2/STAT3 信号通路。综上所述，我们的研究结果表明，microRNA-133b 的过度调节通过靶向 EGFR 抑制顺铂诱导的 NSCLC 细胞的增殖，该作用是通过 PI3K/Akt 和 JAK2/STAT3 信号通路实现的。
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