Department of Thoracic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Department of Cardiac Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
Mol Med Rep. 2019 Mar;19(3):1491-1500. doi: 10.3892/mmr.2018.9775. Epub 2018 Dec 18.
Increasing evidence suggests that the dysregulation of microRNAs (miRNAs) has an important role in the progression of human cancer, including ESCC. However, the exact functions and mechanisms of miRNAs in ESCC remain largely unclear. The aim of the present study was to investigate the expression and biological functions of miRNAs in ESCC and reveal the underlying molecular mechanisms. miRNA microarray and reverse transcription‑quantitative polymerase chain reaction analyses were performed, which identified and confirmed that miR‑206 was significantly downregulated in ESCC tissues and cell lines. Its low expression was associated with lymph node metastasis, advanced TNM stage and N classification, as well as poorer overall survival in patients with ESCC. CCK‑8 and flow cytometry assays demonstrated that ectopic miR‑206 expression inhibited ESCC cell proliferation and induced cell apoptosis. In addition, MET proto‑oncogene, receptor tyrosine kinase (c‑Met), a well‑known oncogene, was a direct target of miR‑206. An inverse correlation between the levels of miR‑206 and c‑Met mRNA in ESCC tissue samples was confirmed. Notably, c‑Met overexpression inhibited the effects of miR‑206 on the proliferation and apoptosis of ESCC cells. Additionally, it was confirmed that the tumor‑suppressive functions of miR‑206 may have contributed to the inactivation of the c‑Met/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. In conclusion, the findings of the present study suggested that miR‑206 exerts its anti‑cancer functions via the c‑Met/AKT/mTOR signaling pathway, providing a novel candidate prognostic factor and a potential therapeutic target in ESCC.
越来越多的证据表明，微小 RNA（miRNA）的失调在人类癌症的进展中起着重要作用，包括食管鳞癌（ESCC）。然而，miRNA 在 ESCC 中的确切功能和机制在很大程度上仍不清楚。本研究旨在探讨 miRNA 在 ESCC 中的表达和生物学功能，并揭示其潜在的分子机制。进行了 miRNA 微阵列和逆转录-定量聚合酶链反应分析，鉴定并证实 miR-206 在 ESCC 组织和细胞系中显著下调。其低表达与淋巴结转移、晚期 TNM 分期和 N 分类以及 ESCC 患者的总体生存率较差相关。CCK-8 和流式细胞术检测表明，外源性 miR-206 表达抑制 ESCC 细胞增殖并诱导细胞凋亡。此外，原癌基因 MET 受体酪氨酸激酶（c-Met）是 miR-206 的直接靶基因。在 ESCC 组织样本中证实了 miR-206 水平与 c-Met mRNA 之间的负相关。值得注意的是，c-Met 过表达抑制了 miR-206 对 ESCC 细胞增殖和凋亡的影响。此外，还证实了 miR-206 的肿瘤抑制功能可能归因于 c-Met/蛋白激酶 B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路的失活。综上所述，本研究的结果表明，miR-206 通过 c-Met/AKT/mTOR 信号通路发挥其抗癌功能，为 ESCC 提供了一个新的候选预后因素和潜在的治疗靶点。
