首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (5): 762-767.doi: 10.3969/j.issn.1006-7795.2023.05.009

• 恶性肿瘤诊治进展 • 上一篇    下一篇

miR-150靶向调控IGF2BP2对肝癌恶性表型的影响机制

谭宇博,苏卜伊努尔·吐尔洪,黄静,张婷婷,刘俊杰,沙娅·玛哈提*   

  1. 新疆医科大学第一附属医院肿瘤中心,省部重点中亚高发病成因与防治国家重点实验室, 乌鲁木齐 830054
  • 收稿日期:2023-07-18 出版日期:2023-10-20 发布日期:2023-10-26
  • 通讯作者: 沙娅·玛哈提 E-mail:sasa870716@126.com
  • 基金资助:
    新疆维吾尔自治区自然科学基金青年项目(2021D01C351),新疆医科大学大学生创新创业基金项目(CX2021010),省部重点中亚高发病成因与防治国家重点实验室青年项目(SKL-HIDCA-2019-33),省部重点中亚高发病成因与防治国家重点实验室面上项目(SKL-HIDCA-2020-SC5)

The mechanism of miR-150 targeted regulation of IGF2BP2 on the malignant phenotype of liver cancer

Tan Yubo, Suboyinuer Tuerhong, Huang Jing, Zhang Tingting, Liu Junjie, Shaya Mahati*   

  1. Department of Tumor Center, First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathgenesis, Prevention and Treatment of High Incidence Diseases in Central Asia,Urumqi 830054, China
  • Received:2023-07-18 Online:2023-10-20 Published:2023-10-26
  • Supported by:
    This study was supported by Xinjiang Natural Science Foundation Youth Project (2021D01C351),Xinjiang Medical University Student Innovation Venture Fund Project (CX2021010),Young Project of State Key Laboratory of Pathgenesis, Prevention and Treatment of High Incidence Diseases in Central Asia (SKL-HIDCA-2019-33),Project of State Key Laboratory of Pathgenesis, Prevention and Treatment of High Incidence Diseases in Central Asia(SKL-HIDCA-2020-SC5).

摘要: 目的  本研究旨在阐明miR-150在肝细胞癌(hepatocellular carcinoma, HCC)中的作用和靶点。方法  采用热图分析方法,从癌症基因组图谱(The Cancer Genome Atlas)数据库下载的6组HCC组织与邻近肝组织之间差异表达的miRNA。采用实时定量聚合酶链反应检测miR-150在HCC组织和细胞系中的表达;采用侵袭小室试验评估HCC细胞的增殖、侵袭和迁移潜能。此外,利用TargetScan软件用于预测miR-150的潜在靶标,并通过蛋白印迹(Western blotting)和荧光素酶法测定miR-150与其靶基因的关系。结果  通过热图分析法,发现在HCC组织中有31个miRNA表达异常,其中miR-150表达差异最为显著,且与患者预后密切相关。细胞实验上,高表达miR-150可通过调节胰岛素样生长因子2-mRNA结合蛋白2 (recombinant insulin like growth factor 2 mRNA binding protein 2,IGF2BP2) 的表达显著降低人肝癌细胞株SMMC-7721和HepG2细胞的增殖、迁移和侵袭能力。结论  miR-150通过调控IGF2BP2抑制HCC细胞的增殖、迁移和侵袭,为HCC提供了新的治疗靶点。

关键词: 肝癌, miR-150, IGF2BP2, 侵袭转移

Abstract: Objective  To elucidate the impacts and targets of miR-150 in hepatocellular carcinoma (HCC). Methods  Heatmap analysis was utilized for screening the differentially expressed miRNAs between six sets of HCC tissues and adjacent liver tissues downloaded from The Cancer Genome Atlas database. Quantitative real-time polymerase chain reaction was employed for assessing miR-150 expression in HCC tissues and cell lines. Then, cell counting Kit-8 assay and Transwell assay separately were conducted to evaluate the proliferation, invasion and migration potential of HCC cells. Besides, TargetScan software was utilized for predicting the potential targets of miR-150. Moreover, the relationship between miR-150 and its target genes were determined by Western blotting and luciferase reporter assay. Results  We identified 31 deregulated miRNAs (including the most significantly down-regulated miR-150) in HCC tissues. MiR-150 expression was significantly reduced in HCC tissues and cell lines. Highly expressed miR-150 significantly increased the 5-year survival rate of HCC patients. Meanwhile, miR-150 induced a significant reduction of the cell proliferation, migration, and invasion potentials of human hepatocarcinoma cells (SMMC-7721and HepG2). We found miR-150 directly target recombinant insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) and decrease human phosphorylation phosphotylinosital 3-kinase and protein kinase B signal (p-PI3K/Akt) pathway. Conclusions  These results suggested that miR-150 restrained proliferation, migration, and invasion of HCC cells by regulating IGF2BP2, providing a new therapeutic target for HCC.

Key words: hepatocellular carcinoma, miR-150, IGF2BP2, migration and invasion

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