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Alcoholic hepatitis (AH) is identified as an inflammatory syndrome with high morbidity and mortality as a result of severe hepatocellular dysfunction and liver injury. Accumulated studies indicated that miRNAs are involved in AH. The potential effect of miR‐451a in AH mice was examined in the current study. A mice AH model was established and the miR‐451a expression in AH mice compared with the sham group was tested by real‐time polymerase chain reaction (qRT‐PCR). AH mice were injected with pre‐miR‐451a lentivirus for miR‐451a overexpression and histone deacetylase (HDAC8) lentivirus for HDAC8 overexpression in AH mice. The underlying mechanisms were explored by searching the potential target genes of miR‐451a in miRanda database and then we confirmed this. We found that miR‐451a expression was significantly decreased in AH mice compared with the sham group. Moreover, miR‐451a overexpression alleviated alcohol‐induced liver inflammation and injuries of AH mice. Additionally, further mechanism exploration disclosed that HDAC8 was a target of miR‐451a. The protective effect of miR‐451a on AH in AH mice was abolished by HDAC8 overexpression. In summary, miR‐451a ameliorates AH via repressing HDAC8‐mediated proinflammatory response.

Abnormal expression of microRNAs (miRNAs) is frequently occurred in prostate cancer (PCa). This study was aimed to investigate the biological roles of miR‐451a in PCa. Quantitative real‐time PCR (qRT‐PCR) and Western blot were employed to investigate the expression levels of miR‐451a and proteasome (prosome, macropain) subunit, beta type, 8 (PSMB8) in PCa cell lines. Luciferase activity reporter assay was used to verify the connection between miR‐451a and PSMB8. in vitro functional experiments were performed to measure the effects of miR‐451a or PSMB8 on PCa cell proliferation, colony formation ability, cell invasion, and cell apoptosis. miR‐451a expression was downregulated, whereas PSMB8 expression was upregulated in PCa cell lines. Luciferase activity reporter assay confirmed the direct connection between miR‐451a and PSMB8. Overexpression of miR‐451a inhibits PCa cell proliferation, colony formation, cell invasion and promotes cell apoptosis, while the overexpression of PSMB8 caused the opposite effects. Moreover, rescue experiments confirmed PSMB8 was a functional target of miR‐451a. In conclusion, this study provides novel insights into the role of miR‐451a in PCa, and the results demonstrated miR‐451a could inhibit PCa progression by targeting PSMB8.

Recent analyses of our microRNA (miRNA) expression signatures obtained from several types of cancer have provided novel information on their molecular pathology. In renal cell carcinoma (RCC), expression of microRNA-451a (miR-451a) was significantly downregulated in patient specimens and low expression of miR-451a was significantly associated with poor prognosis of RCC patients (P = .00305) based on data in The Cancer Genome Atlas. The aims of the present study were to investigate the antitumor roles of miR-451a and to identify novel oncogenic networks it regulated in RCC cells. Ectopic expression of miR-451a significantly inhibited cancer cell migration and invasion by RCC cell lines, suggesting that miR-451a had antitumor roles. To identify oncogenes regulated by miR-451a in RCC cells, we analyzed genome-wide gene expression data and examined information in in silico databases. A total of 16 oncogenes and were found to be possible targets of miR-451a regulation. Interestingly, high expression of 9 genes (PMM2, CRELD2, CLEC2D, SPC25, BST2, EVL, TBX15, DPYSL3, and NAMPT) was significantly associated with poor prognosis. In this study, we focused on phosphomannomutase 2 (PMM2), which was the most strongly associated with prognosis. Overexpression of PMM2 was detected in clinical specimens and Spearman's rank test indicated a negative correlation between the expression levels of miR-451a and PMM2 (P = .0409). Knockdown of PMM2 in RCC cells inhibited cancer cell migration and invasion, indicating overexpression of PMM2 could promote malignancy. Analytic strategies based on antitumor miRNAs is an effective tool for identification of novel pathways of cancer.

We previously demonstrated that acidic bile activates NF‐κB, deregulating the expression of oncogenic miRNA markers, in pre‐malignant murine laryngopharyngeal mucosa. Here, we hypothesize that the in vitro exposure of human hypopharyngeal cells to acidic bile deregulates cancer‐related miRNA markers that can be reversed by BAY 11‐7082, a pharmacologic NF‐κB inhibitor. We repetitively exposed normal human hypopharyngeal primary cells and human hypopharyngeal keratinocytes to bile fluid (400 μmol/L), at pH 4.0 and 7.0, with/without BAY 11‐7082 (20 μmol/L). We centred our study on the transcriptional activation of oncogenic miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375, miR‐451a and NF‐κB‐related genes, previously linked to acidic bile‐induced pre‐neoplastic events. Our novel findings in vitro are consistent with our hypothesis demonstrating that BAY 11‐7082 significantly reverses the acidic bile‐induced oncogenic miRNA phenotype, in normal hypopharyngeal cells. BAY 11‐7082 strongly inhibits the acidic bile‐induced up‐regulation of miR‐192 and down‐regulation of miR‐451a and significantly decreases the miR‐21/375 ratios, previously related to poor prognosis in hypopharyngeal cancer. This is the first in vitro report that NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in normal human hypopharyngeal cells, suggesting that acidic bile‐induced events are directly or indirectly dependent on NF‐κB signalling.