MiR-27a-3p enhances the cisplatin sensitivity in hepatocellular carcinoma cells through inhibiting PI3K/Akt pathway.

MicroRNAs (miRNAs) play an important role in drug resistance, and it is reported that miR-27a-3p regulated the sensitivity of cisplatin in breast cancer, lung cancer and ovarian cancer. However, the relationship between miR-27a-3p and chemosensitivity of cisplatin in hepatocellular carcinoma (HCC) was unclear, especially the underlying mechanism was unknown. In the present study, we analyzed miR-27a-3p expression levels in 372 tumor tissues and 49 adjacent tissues in HCC samples from TCGA database, and found that the miR-27a-3p was down-regulated in HCC tissues. The level of miR-27a-3p was associated with metastasis, Child-Pugh grade and race. MiR-27a-3p was regarded as a favorable prognosis indicator for HCC patients. Then, miR-27a-3p was overexpressed in HepG2 cell, and was knocked down in PLC cell. Next, we conducted a series of in vitro assays, including MTT, apoptosis and cell cycle assays to observe the biological changes. Further, inhibitor rate and apoptosis rate were detected with pre- and post-cisplatin treatment in HCC. The results showed that overexpression of miR-27a-3p repressed the cell viability, promoted apoptosis and increased the percentage of cells in G0/G1 phase. Importantly, overexpression of miR-27a-3p significantly increased the inhibitor rate and apoptosis rate with cisplatin intervention. Besides, we found that miR-27a-3p added cisplatin sensitivity potentially through regulating PI3K/Akt signaling pathway. Taken together, miR-27a-3p acted as a tumor suppressor gene in HCC cells, and it could be useful for modulating cisplatin sensitivity in chemotherapy.

Yang Y ，Yang Z ，Zhang R ，Jia C ，Mao R ，Mahati S ，Zhang Y ，Wu G ，Sun YN ，Jia XY ，Aimudula A ，Zhang H ，Bao Y ... -  《-》

MiR-128-3p overexpression sensitizes hepatocellular carcinoma cells to sorafenib induced apoptosis through regulating DJ-1.

Guo XL ，Wang HB ，Yong JK ，Zhong J ，Li QH ... -  《-》

MicroRNA-27a-3p inhibits cell viability and migration through down-regulating DUSP16 in hepatocellular carcinoma.

MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down-regulated expression of miR-27a-3p in hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK-8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR-27a-3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay. miR-27a-3p up-regulation by transfection with miR-27a-3p mimics attenuated SMMC-7721 and HepG2 cell viability, invasion as well as migration, obviously. Moreover, we found that dual specificity phosphatase 16 (DUSP16), also known as mitogen-activated protein kinase phosphatase 7 (MKP-7), is a target of miR-27a-3p. DUSP16 expression was obvious decrease by miR-27a-3p at both transcriptional and protein levels in both SMMC-7721 and HepG2 cells. DUSP16 expression in tissues of HCC was up-regulated in comparison with that in tissues of adjacent liver based on the TCGA database. Overexpression of DUSP16 significantly reversed the cell changes in viability, invasion and migration which resulted from miR-27a-3p up-regulation in SMMC-7721 and HepG2 cells. Our findings contribute to current understanding of the functions of miR-27a-3p and suggest a mechanism by which miR-27a-3p plays an anti-tumor role in the development of HCC by targeting DUSP16.

Li JM ，Zhou J ，Xu Z ，Huang HJ ，Chen MJ ，Ji JS ... -  《-》

Midazolam inhibits proliferation and accelerates apoptosis of hepatocellular carcinoma cells by elevating microRNA-124-3p and suppressing PIM-1.

Recently, the impact of microRNAs (miRNAs) has been identified in hepatocellular carcinoma (HCC), this study was designed to assess the effects of miR-124-3p and midazolam (MDZ) in HCC with the involvement of PIM-1. HepG2 human HCC cells were selected for our study, which were treated with different concentrations of MDZ. The gain- and loss-of-function experiments were performed to elucidate the migration, invasion, proliferation, colony formation ability, cell cycle, and apoptosis of HepG2 cells upon treatment of MDZ, miR-124-3p mimics, or miR-124-3p inhibitor. The expression levels of miR-124-3p, PIM-1, Bax, Bcl-2, P21, and Ki-67 in HepG2 cells were assessed by reverse transcription quantitative polymerase chain reaction and western blot analysis. Moreover, HepG2 cell growth in vivo was measured by subcutaneous tumorigenesis in nude mice, and the target relation between miR-124-3p and PIM-1 was evaluated using dual luciferase reporter gene assay. We have found that after treated with overexpression of miR-124-3p and MDZ, there exhibited elevated miR-124-3p, declined expression of PIM-1, attenuated migration, invasion, proliferation and colony formation ability, and promoted apoptosis of HepG2 cells. Additionally, it could be observed that the tumor volume and weight were all reduced upon treatment of overexpression of miR-124-3p and MDZ. Meanwhile, the results in the HepG2 cells that treated with down-regulated miR-124-3p were the opposite. Furthermore, PIM-1 was found to be a target gene of miR-124-3p. Our study found that MDZ could inhibit proliferation and accelerate apoptosis of HCC cells by elevation of miR-124-3p and suppressing PIM-1, which may be an effective method in the treatment of HCC.

Qi Y ，Yao X ，Du X 《-》

MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A.

Ohta K ，Hoshino H ，Wang J ，Ono S ，Iida Y ，Hata K ，Huang SK ，Colquhoun S ，Hoon DS ... -  《Oncotarget》