Hua Shengni, Quan Yingyao, Zhan Meixiao, Liao Huaxin, Li Yong, Lu Ligong
Zhuhai Interventional Medical Center, Zhuhai Precision Medical Center, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Zhuhai, 519000 China.
2Biomedicine Institute, College of Life Science, Jinan University, Guangzhou, 510632 China.
Cancer Cell Int. 2019 Jul 30;19:203. doi: 10.1186/s12935-019-0919-6. eCollection 2019.
() is an antioxidant enzyme reportedly overexpressed in hepatocellular carcinoma (HCC); however, the detailed function and mechanisms of TXNRD1 in HCC remain obscure. In this study, we investigated the miR-125b-5p-specific regulation of levels and its effect on HCC cells.
We detected miR-125b-5p levels in human HCC tissue samples through quantitative reverse transcription polymerase chain reaction (qRT-PCR), and in vitro experiments were employed to investigate the effect of miR-125b-5p on HCC cell proliferation, migration, and invasion. Additionally, we examined miR-125b-5p-mediated changes in TXNRD1 levels by qRT-PCR and western blotting, and a dual luciferase-reporter assay was conducted to confirm direct targeting of the 3' untranslated region of TXNRD1 mRNA by miR-125b-5p.
miR-125b-5p expression was reduced in HCC tissues relative to that in matched para-carcinoma tissues; this finding was verified in HCC cohorts from the Gene Expression Omnibus and The Cancer Genome Atlas. Additionally, low miR-125b-5p expression was associated with poor prognosis in HCC patients, and gene-set enrichment analysis indicated that miR-125b-5p levels were associated with HCC proliferation and metastasis. As predicted, overexpressing miR-125b-5p restrained the proliferation, migration, and invasion of Huh7 and SK-Hep-1 cells and forced expression of the miR-125b-5p-downregulated TXNRD1 mRNA and protein levels in HCC cells. Moreover, dual luciferase-reporter assays revealed that miR-125b-5p targets to directly regulate its expression, whereas overexpression abolishes the inhibitory effect of miR-125b-5p on HCC cell proliferation, migration, and invasion.
These results demonstrated miR-125b-5p as a tumor suppressor in HCC through its inhibition of , thereby suggesting it as a potential target for the clinical treatment of HCC.
据报道，（）是一种抗氧化酶，在肝细胞癌（HCC）中过表达；然而，TXNRD1在HCC中的详细功能和机制仍不清楚。在本研究中，我们研究了miR-125b-5p对TXNRD1水平的特异性调控及其对HCC细胞的影响。
我们通过定量逆转录聚合酶链反应（qRT-PCR）检测了人HCC组织样本中的miR-125b-5p水平，并采用体外实验研究了miR-125b-5p对HCC细胞增殖、迁移和侵袭的影响。此外，我们通过qRT-PCR和蛋白质印迹法检测了miR-125b-5p介导的TXNRD1水平变化，并进行了双荧光素酶报告基因测定以确认miR-125b-5p直接靶向TXNRD1 mRNA的3'非翻译区。
与配对的癌旁组织相比，HCC组织中miR-125b-5p表达降低；这一发现已在来自基因表达综合数据库和癌症基因组图谱的HCC队列中得到验证。此外，低miR-125b-5p表达与HCC患者的不良预后相关，基因集富集分析表明miR-125b-5p水平与HCC增殖和转移相关。如预期的那样，过表达miR-125b-5p抑制了Huh7和SK-Hep-1细胞的增殖、迁移和侵袭，并使HCC细胞中miR-125b-5p下调的TXNRD1 mRNA和蛋白质水平强制表达。此外，双荧光素酶报告基因测定表明，miR-125b-5p靶向TXNRD1以直接调节其表达，而TXNRD1过表达消除了miR-125b-5p对HCC细胞增殖、迁移和侵袭的抑制作用。
这些结果表明miR-125b-5p通过抑制TXNRD1在HCC中作为肿瘤抑制因子，从而提示其作为HCC临床治疗的潜在靶点。
