miR-30c-5p 通过抑制 PI3K/AKT 信号通路抑制食管鳞状细胞癌的进展

IF 2.3 3区 医学 Q3 ONCOLOGY Thoracic Cancer Pub Date : 2024-09-18 DOI:10.1111/1759-7714.15427
Haochun Shi, Binyang Pan, Jiaqi Liang, Benjie Cai, Gujie Wu, Yunyi Bian, Guangyao Shan, Shencheng Ren, Yiwei Huang, Weigang Guo
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引用次数: 0

摘要

背景食管鳞状细胞癌(ESCC)是最常见的恶性肿瘤之一,发病率高、预后差。揭示 ESCC 的进展机制和开发新的治疗靶点仍然至关重要。本研究旨在阐明miR-30c-5p调控ESCC恶性进展的分子机制。方法利用TCGA、GEO等数据集分析miR-30c-5p在ESCC和邻近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和创伤愈合实验研究了miR-30c-5p对TE-1和Eca9706细胞增殖、迁移和侵袭的影响。结果miR-30c-5p在ESCC组织中显著下调,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,miR-30c-5p与PIK3CA mRNA直接相互作用,抑制了后续信号通路的激活。PIK3CA激活剂可消除miR-30c-5p模拟物对ESCC进展的抑制作用,而PIK3CA抑制剂可挽救miR-30c-5p抑制剂组细胞的促进作用。结论综上所述,我们首次发现miR-30c-5p通过抑制PI3K/AKT信号通路来抑制ESCC的增殖、侵袭和迁移,这项研究有望为治疗ESCC提供新的见解和潜在的治疗靶点。
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miR‐30c‐5p inhibits esophageal squamous cell carcinoma progression by repressing the PI3K/AKT signaling pathway
BackgroundEsophageal 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.MethodsTCGA, 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.ResultsmiR‐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.ConclusionsIn 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.
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来源期刊
Thoracic Cancer
Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM
CiteScore
5.20
自引率
3.40%
发文量
439
审稿时长
2 months
期刊介绍: Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.
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