miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFβR2

• Hao-Tian Liu ^[1] ; Cheng-Piao Luo ^[2] ; Meng-Jie Jiang ^[1] ; Zhu-Jian Deng ^[1] ; Yu-Xian Teng ^[1] ; Jia-Yong Su ^[1] ; Li-Xin Pan ^[1] ; Liang Ma ^[1] ; Ping-Ping Guo ^[1] ; Jian-Hong Zhong ^[1]
  1. [1] Guangxi Medical University

     Guangxi Medical University

     China

     
  2. [2] Department of Pathology, Guangxi Medical University Cancer Hospital, Nanning, China
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 25, Nº. 10 (October), 2023, págs. 2960-2971
• Idioma: inglés
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• Resumen

  • Objective Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor β receptor 2 (TGFβR).

    Methods We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial–mesenchymal transition (EMT) were assessed, while its effects on TGFβR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay.

    Results Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFβR2.

    Conclusion The miRNA miR-17-5p can negatively regulate the expression of TGFβR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC.