General Medicine Department, Yantaishan Hospital, Yantai, China.
Health management center, Qingdao Central Hospital, Qingdao, China.
Neoplasma. 2020 Sep;67(5):1042-1053. doi: 10.4149/neo_2020_191019N1062. Epub 2020 Jun 2.
microRNA-34a (miR-34a) and microRNA-1251-5p (miR-125a-5p) were considered as tumor suppressors in hepatocellular carcinoma (HCC). Nevertheless, the modulatory mechanisms of miR-34a and miR-125a-5p in HCC haven't been completely understood. The levels of metastasis-associated with colon cancer 1 (MACC1) and miRNAs (miR-34a and miR-125a-5p) were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and the levels of associated proteins were detected by western blot assay. Cell proliferation and metastasis were examined via Cell Counting Kit-8 (CCK-8) and transwell assays, respectively. Cell apoptosis was measured through flow cytometry. The effect of MACC1 on HCC in vivo was explored via xenograft assay. Dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay were implemented to explore the target correlation. The expression of MACC1 was upregulated in HCC tissues and cells. Knockdown of MACC1 inhibited proliferation and metastasis but expedited apoptosis of HCC cells and the repression of tumor growth in vivo was evoked by MACC1 downregulation. Both miR-34a and miR-125a-5p directly targeted MACC1 and repressed the expression of MACC1 in HCC cells. Overexpression of miR-34a or miR-125a-5p restrained cell proliferation and metastasis while induced apoptosis by downregulating MACC1 in HCC cells. miR-34a and miR-125a-5p repressed phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signal pathway via reducing MACC1 in HCC cells. miR-34a and miR-125a-5p refrained proliferation and metastasis while motivated apoptosis in HCC cells through the PI3K/AKT/mTOR pathway by repressing MACC1. miR-34a and miR-125a-5p might be splendid biomarkers in the therapeutic strategies for HCC.
微小 RNA-34a（miR-34a）和微小 RNA-1251-5p（miR-125a-5p）被认为是肝癌（HCC）中的肿瘤抑制因子。然而，miR-34a 和 miR-125a-5p 在 HCC 中的调节机制尚未完全阐明。通过定量实时聚合酶链反应（qRT-PCR）测定转移相关结肠癌基因 1（MACC1）和 miRNA（miR-34a 和 miR-125a-5p）的水平，并通过 Western blot 检测相关蛋白的水平。通过细胞计数试剂盒-8（CCK-8）和 Transwell 测定分别检测细胞增殖和转移。通过流式细胞术测量细胞凋亡。通过异种移植试验探索 MACC1 对 HCC 的体内作用。实施双荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）试验以探索靶标相关性。MACC1 在 HCC 组织和细胞中表达上调。MACC1 敲低抑制 HCC 细胞的增殖和转移，但加速细胞凋亡，并通过下调 MACC1 抑制体内肿瘤生长。miR-34a 和 miR-125a-5p 均可直接靶向 MACC1，并抑制 HCC 细胞中 MACC1 的表达。miR-34a 或 miR-125a-5p 的过表达通过下调 HCC 细胞中的 MACC1 来抑制细胞增殖和转移，同时诱导细胞凋亡。miR-34a 和 miR-125a-5p 通过降低 HCC 细胞中的 MACC1 来抑制 PI3K/蛋白激酶 B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路，从而抑制 HCC 细胞的增殖和转移，同时通过该通路诱导细胞凋亡。miR-34a 和 miR-125a-5p 通过抑制 MACC1，可能成为 HCC 治疗策略中的良好生物标志物。
