Department of Pathology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China.
Department of Pathology, The Third People's Hospital of Mianyang, Mianyang, Sichuan 621000, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11955. Epub 2021 Mar 24.
Esophageal squamous cell carcinoma (ESCC) is one of the most debilitating and invasive tumors. Although previous reports have demonstrated the critical role microRNA‑181a (miR‑181a) serves in the progression of ESCC, how miR‑181a induces epithelial‑mesenchymal transition (EMT) remains to be elucidated. In the present study, the expression profiles of TGF‑β1 and Smad4 proteins in 88 patients with ESCC and 21 adjacent non‑cancerous tissues were analyzed using immunohistochemistry. The expression of miR‑181a in ESCC cells (ECA109 and TE‑1) and HEEC was analyzed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The role of miR‑181a in ESCC was analyzed using miR‑181a mimics and inhibitor in the same system. Migration, proliferation and apoptosis of cells were assessed using wound‑healing assays and cell proliferation assays and flow cytometry, respectively. The expression levels of TGF‑β1 and Smad4 in ESCC cell lines transfected with miR‑181a mimics and inhibitor were measured using RT‑qPCR and western blotting. The expression of E‑cadherin and vimentin was also assessed following transfection. The findings demonstrated that expression of TGF‑β1 was upregulated, in contrast to Smad4 expression which was downregulated. Expression levels of Smad4 affected the prognosis of patients with ESCC. Higher expression of miR‑181a promoted migration and proliferation but inhibited apoptosis of ESCC cells. miR‑181a promoted EMT by modulating Smad4 expression in ESCC cells. Overall, these findings revealed that miR‑181a induced EMT in ESCC via the TGF‑β/Smad pathway in ESCC. Consequently, miR‑181a is a potential novel target against ESCC.
食管鳞状细胞癌（ESCC）是最具侵袭性和致残性的肿瘤之一。尽管之前的报告表明 microRNA-181a（miR-181a）在 ESCC 的进展中起关键作用，但 miR-181a 如何诱导上皮-间充质转化（EMT）仍有待阐明。在本研究中，通过免疫组织化学分析了 88 例 ESCC 患者和 21 例相邻非癌组织中 TGF-β1 和 Smad4 蛋白的表达谱。采用逆转录-定量聚合酶链反应（RT-qPCR）分析了 miR-181a 在 ESCC 细胞（ECA109 和 TE-1）和 HEEC 中的表达。在相同系统中，通过 miR-181a 模拟物和抑制剂分析了 miR-181a 在 ESCC 中的作用。通过划痕愈合试验、细胞增殖试验和流式细胞术分别评估细胞的迁移、增殖和凋亡。通过 RT-qPCR 和 Western blot 测定转染 miR-181a 模拟物和抑制剂的 ESCC 细胞系中 TGF-β1 和 Smad4 的表达水平。转染后还评估了 E-钙粘蛋白和波形蛋白的表达。结果表明，TGF-β1 的表达上调，而 Smad4 的表达下调。Smad4 的表达水平影响 ESCC 患者的预后。miR-181a 表达水平升高促进 ESCC 细胞的迁移和增殖，但抑制凋亡。miR-181a 通过调节 ESCC 细胞中的 Smad4 表达促进 EMT。总之，这些发现表明，miR-181a 通过 TGF-β/Smad 通路在 ESCC 中诱导 EMT。因此，miR-181a 是一种针对 ESCC 的潜在新型靶点。
