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Background Thioredoxin reductase 1 ( TXNRD1 ) 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 TXNRD1 levels and its effect on HCC cells. Methods 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. Results 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 TXNRD1 to directly regulate its expression, whereas TXNRD1 overexpression abolishes the inhibitory effect of miR-125b-5p on HCC cell proliferation, migration, and invasion. Conclusions These results demonstrated miR-125b-5p as a tumor suppressor in HCC through its inhibition of TXNRD1 , thereby suggesting it as a potential target for the clinical treatment of HCC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0919-6) contains supplementary material, which is available to authorized users.

This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.