Biomedical Experimental Center, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University School of Health Science Center, Xi'an 710061, Shaanxi, China.
Crit Rev Eukaryot Gene Expr. 2023;33(3):71-84. doi: 10.1615/CritRevEukaryotGeneExpr.v33.i3.70.
Hepatocellular carcinoma (HCC) is one common cancer in the world. Previous studies have shown that miR-17 family members are elevated in most tumors and promote tumor progression. However, there is no comprehensive analysis of the expression and functional mechanism of the microRNA-17 (miR-17) family in HCC. The aim of this study is to comprehensively analyze the function of the miR-17 family in HCC and the molecular mechanism of its role. Bioinfoimatics analysis of the miR-17 family expression profile and its relationship to clinical significance using The Cancer Genome Atlas (TCGA) database, and this result was confirmed using quantitative real-time polymerase chain reaction. miR-17 family members were tested for functional effects through transfection of miRNA precursors and inhibitors, and monitoring cell viability and migration by cell count and wound healing assays. In addition, we using dual-luciferase assay and Western blot demonstrated the targeting relationship between the miRNA-17 family and RUNX3. These members of miR-17 family were highly expressed in HCC tissues, and the overexpression of the miR-17 family promoted the proliferation and migration of SMMC-7721 cells, whereas treatment with anti-miR17 inhibitors caused the opposite effects. Notably, we also found that inhibitors anti-each member of miR-17 can suppress the expression of the entire family member. In addition, they can bind to the 3' untranslated region of RUNX3 to regulate its expression at the translational level. Our results proved that miR-17 family has oncogenic characteristics, overexpression every member of the family contributed to HCC cell proliferation and migration by reducing the translation of RUNX3.
肝细胞癌（HCC）是世界上一种常见的癌症。先前的研究表明，miR-17 家族成员在大多数肿瘤中升高，并促进肿瘤进展。然而，miR-17 家族在 HCC 中的表达和功能机制尚未进行全面分析。本研究旨在全面分析 miR-17 家族在 HCC 中的功能及其作用的分子机制。使用癌症基因组图谱（TCGA）数据库进行 miR-17 家族表达谱及其与临床意义的生物信息学分析，并通过定量实时聚合酶链反应验证该结果。通过转染 miRNA 前体和抑制剂测试 miR-17 家族成员的功能影响，并通过细胞计数和划痕愈合测定监测细胞活力和迁移。此外，我们通过双荧光素酶测定和 Western blot 证实了 miRNA-17 家族与 RUNX3 之间的靶向关系。miR-17 家族成员在 HCC 组织中高表达，miR-17 家族的过表达促进了 SMMC-7721 细胞的增殖和迁移，而抗 miR17 抑制剂的处理则产生了相反的效果。值得注意的是，我们还发现抗每个 miR-17 成员的抑制剂都可以抑制整个家族成员的表达。此外，它们可以与 RUNX3 的 3'非翻译区结合，从而在翻译水平上调节其表达。我们的结果证明 miR-17 家族具有致癌特征，家族成员的过表达通过降低 RUNX3 的翻译促进 HCC 细胞的增殖和迁移。
