miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1

Abstract

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.

Dysregulation of microRNA expression during the progression of colorectal tumors

“…28 However, another study demonstrated that expression of miRNA-125b-5p is correlated with a poor prognosis in hepatocellular carcinoma patients by targeting thioredoxin-1 (TXNRD1), a key molecule associated with intracellular redox homeostasis that promotes energy and carbohydrate metabolism. 29 In this study, miRNA-125b-5p was upregulated in invasive CRC, compared with samples isolated from normal samples, although this finding was not consistent with previous studies. 28,29 Regarding miRNA-143-3p, we demonstrated that its expression was correlated with invasive CRCs compared with intramucosal carcinomas.…”

“…29 In this study, miRNA-125b-5p was upregulated in invasive CRC, compared with samples isolated from normal samples, although this finding was not consistent with previous studies. 28,29 Regarding miRNA-143-3p, we demonstrated that its expression was correlated with invasive CRCs compared with intramucosal carcinomas. A previous study revealed that miRNA-143-3p overexpression suppressed cell proliferation, migration and invasion in CRC.…”

Downregulation of circular RNA circPVT1 restricts cell growth of hepatocellular carcinoma through downregulation of Sirtuin 7 via microRNA‐3666

“…For example, a recent study reports that circPVT1 also functions as a sponge of miR‐203 in HCC . Interestingly, other reported target miRNAs of circPVT1, such as miR‐145 and miR‐125b, play a key role in HCC progression . Therefore, whether circPVT1 regulates HCC progression through these miRNAs warrants further validation.…”

<p>The Emerging Roles of miR-125b in Cancers</p>

“…The downregulation of miR-125b causes the overexpression of EIF5A2, which is known to be associated with proliferation and poor prognosis in patients with CRC and NSCLC. 39,[69][70][71] MiR-100 reduces the protein level of Angpt2, which is an essential molecule for angiogenesis, by blocking the mTOR/p70S6K signaling pathway. It has been demonstrated that miR-125b can cause excessive angiogenesis by affecting the proliferation of endothelial cells.…”