Our meta-analysis provided the evidence that miR-21, miR-200c, miR-125b, miR-148b, miR-365, miR-124, miR-32, miR-146a, and miR-375 can act as prognostic biomarkers in NSCLC.

Histone deacetylase inhibitors (HDACIs) are emerging as a novel class of anti-tumor drugs. But the effect of HDACIs in tumors treatment has been disappointing, which mainly due to the acquisition of resistance to HDACIs. However, the underlying mechanisms have not been clearly understood. In this study, it was found that HDACIs SAHA and TSA increased P-gp expression in CRC cells, which has been well known to contribute to drug resistant. The mechanisms underlying these effects were investigated. We showed that HDACIs enhanced transcriptional activity of P-gp protein encoding gene ABCB1. HDACIs treatment also increased the protein and mRNA expression of STAT3, but not PXR, CAR, Foxo3a or β-catenin, which are known to be involved in ABCB transcription regulation. Interestingly, knockdown of STAT3 significantly attenuated HDACIs-induced P-gp up-regulation in colorectal cancer cells, suggesting that STAT3 plays a crucial role in HDACIs-up-regulated P-gp. Furthermore, this study revealed for the first time that HDACIs enhanced the stability of ABCB1 at post-transcriptional level. Taken together, these results proved that HDACIs induced P-gp expression by two distinct ways, transcriptional activation and mRNA stabilization. Our results suggested that more attention should be paid to the cancer treatment using HDACIs since they will induce multidrug resistance in cancer cells.

micro (mi)‑RNAs are a class of small non‑coding RNAs that regulate gene expression by binding to the 3'‑untranslated region of mRNA, which may lead to mRNA degradation or transcription regulation. Previous studies indicated that miRNAs are important for the pathogenesis of human cancer. miR‑375 has been implicated in various tumor types; however, the biological activity in human non‑small cell lung carcinoma (NSCLC) cells remains to be fully elucidated. The purpose of the present study was to investigate the biological importance of miR‑375 in human NSCLC cells. The expression of miRNAs and mRNA was determined using reverse transcription‑quantitative polymerase chain reaction. Cell proliferation was analyzed using a Cell Counting kit‑8 assay. Cell apoptosis was analyzed using a fluorescence‑activated cell sorting assay. The migration and invasion abilities of cells were evaluated using an in vivo mouse model. Dual‑luciferase assay and western blotting were used to determine the potential target of miR‑375. The results indicated that the expression of miR‑375 in human NSCLC cells was significantly downregulated and induction of miR‑375 may inhibit the proliferation of human NSCLC cells by inducing apoptosis. An animal model was used to determine that the upregulation of miR‑375 inhibited the migration and invasion of A549 human NSCLC cells in vivo. It was also determined that human epidermal growth factor receptor 2 (HER‑2) was a direct target gene of miR‑375 and induction of miR‑375 may reduce the expression of HER‑2 in human NSCLC cells. These findings suggested that miR‑375 may act as a potential therapeutic target for human NSCLC cancer in the future.

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