miR-15b, a diagnostic biomarker and therapeutic target, inhibits oesophageal cancer progression by regulating the PI3K/AKT signalling pathway

miR-15b 是一种诊断生物标志物和治疗靶点,它通过调节 PI3K/AKT 信号通路来抑制食管癌进展

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作者:Jie Liu, Haiyan Xu, Nan Wang, Mingyan Sun

Abstract

MicroRNA (miR)-15b is an important regulator in several types of cancer, such as gastric cancer, colorectal cancer and oesophageal squamous cell carcinoma. The PI3K/AKT signalling pathway has been implicated in the growth and metastasis of oesophageal cancer (EC). The aim of the present study was to investigate the biological effects of miR-15b in EC, as well as the underlying mechanism involving the PI3K/AKT signalling pathway. The present study included 74 patients with EC and 74 healthy volunteers. The expression of miR-15b in peripheral blood mononuclear cells (PBMCs) and EC cell lines was evaluated via reverse transcription-quantitative PCR. The receiver operating characteristic curve was plotted to determine the diagnostic significance of miR-15b. EC cell viability, apoptosis, migration and invasion were analysed by conducting MTT, flow cytometry and transwell assays, respectively. Protein expression levels were analysed via western blotting. The results indicated that PBMCs isolated from patients with EC had lower miR-15b expression levels compared with PBMCs isolated from healthy volunteers. In patients with EC, miR-15b expression was strongly associated with tumour size, lymph node metastasis, TNM stage, fibrous membrane invasion and histologic grade. The results of the gain/loss-of-function in vitro experiments indicated that miR-15b inhibited EC cell viability, migration and invasion, facilitated EC cell apoptosis and attenuated the PI3K/AKT signalling pathway in EC109 and TE10 cells. Treatment of EC cells with the PI3K/AKT pathway agonist recilisib displayed the opposite effects, blocking the inhibitory function of miR-15b mimic on EC cell viability, migration and invasion. In summary, the results indicated that miR-15b suppressed EC cell viability, migration and invasion, and promoted EC cell apoptosis by inhibiting the PI3K/AKT signalling pathway.

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