Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Thoracic Surgery and Urology, Shigatse People's Hospital, Shigatse, China.
Thorac Cancer. 2024 Oct;15(30):2206-2216. doi: 10.1111/1759-7714.15427. Epub 2024 Sep 17.
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors, with high incidence and poor prognosis. Revealing mechanisms of ESCC progression and developing new therapeutic targets remains crucial. The aim of this study was to elucidate the molecular mechanism of miR-30c-5p in regulating the malignant progression of ESCC.
TCGA, GEO, and other datasets were used to analyze the differential expression of miR-30c-5p in ESCC and adjacent tissues, and its impact on prognosis. Then the effects of miR-30c-5p on the proliferation, migration, and invasion of TE-1 and Eca9706 cells were investigated through proliferation experiments, transwell and wounding healing assays. The regulatory mechanism of miR-30c-5p on the PI3K/AKT signaling pathway and its interaction in cancer progression were investigated through Western blots, dual-luciferase reporter assay, and rescue experiments.
miR-30c-5p was significantly downregulated in ESCC tissue and represented a poor prognosis. miR-30c-5p mimic significantly inhibited the proliferation, migration, and invasion ability of ESCC, while miR-30c-5p inhibitor significantly promoted tumor cell progression. Through bioinformatic analysis and experimental results, miR-30c-5p interacted directly with PIK3CA mRNA and inhibited subsequent signaling pathway activation. PIK3CA activator could eliminate the inhibitory effects of miR-30c-5p mimic on the progression of ESCC, while PIK3CA inhibitors could rescue the promoting effect of miR-30c-5p inhibitor group cells.
In summary, we found that miR-30c-5p inhibited the proliferation, invasion and migration of ESCC by inhibiting PI3K/AKT signaling pathway for the first time, and this study is expected to provide a novel insight and potential therapeutic target for managing ESCC.
食管鳞状细胞癌(ESCC)是最常见的恶性肿瘤之一,发病率高,预后差。揭示 ESCC 进展的机制并开发新的治疗靶点仍然至关重要。本研究旨在阐明 miR-30c-5p 在调控 ESCC 恶性进展中的分子机制。
使用 TCGA、GEO 和其他数据集分析 miR-30c-5p 在 ESCC 及相邻组织中的差异表达及其对预后的影响。然后通过增殖实验、Transwell 和划痕愈合实验研究 miR-30c-5p 对 TE-1 和 Eca9706 细胞增殖、迁移和侵袭的影响。通过 Western blot、双荧光素酶报告基因检测和挽救实验研究 miR-30c-5p 对 PI3K/AKT 信号通路的调控机制及其在癌症进展中的相互作用。
miR-30c-5p 在 ESCC 组织中显著下调,预示预后不良。miR-30c-5p 模拟物显著抑制 ESCC 的增殖、迁移和侵袭能力,而 miR-30c-5p 抑制剂则显著促进肿瘤细胞的进展。通过生物信息学分析和实验结果,发现 miR-30c-5p 与 PIK3CA mRNA 直接相互作用,抑制后续信号通路的激活。PI3KCA 激活剂可以消除 miR-30c-5p 模拟物对 ESCC 进展的抑制作用,而 PI3KCA 抑制剂可以挽救 miR-30c-5p 抑制剂组细胞的促进作用。
综上所述,我们首次发现 miR-30c-5p 通过抑制 PI3K/AKT 信号通路抑制 ESCC 的增殖、侵袭和迁移,本研究有望为 ESCC 的治疗提供新的思路和潜在的治疗靶点。