EndMT has an important effect on metastasis and progression of tumor. This work will elucidate the effect of miR-494 on EndMT and development of HCC. Therefore, the differential miRNA expression among non-tumorous, para-tumorous and tumorous tissues was analyzed. Moreover, luciferase activities of SIRT3 3′UTR treated with miR-494 were determined. Then human hepatoma cell lines were dealt with mimics or inhibitors of miR-494, migration and proliferation ability were assessed. The expression of SIRT3 and markers of mesenchymal cell were analyzed. The influences of miR-494 on development of HCC through inducing EndMT by targeting SIRT3 and TGF-β/SMAD signaling pathways in hepatoma cell lines were investigated. Xenograft mice were used to explore the potential roles of miR-494 on EndMT and development of HCC in vivo. Our results showed that, compared with non-tumorous tissues, 17 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. In tumor tissues, the miR-494 expression level was much more than the expression of para-tumorous and non-tumorous tissues. MiR-494 suppressed SIRT3 expression, additionally enhanced expression of mesenchymal cell markers, while exerted effects on cell proliferation and migration of hepatoma cell lines. Moreover, the antagomir of miR-494 could protect against development process in xenogarft murine model. In conclusions, our work demonstrated that miR-494 targeted to SIRT3, and was a crucial mediator of EndMT and development of HCC through regulating SIRT3/TGF-β/SMAD signaling pathway. It suggested that aim at SIRT3/TGF-β/SMAD signaling pathway through suppressing the miR-494 expression level, was a feasible therapy strategy for HCC.

Non‑alcoholic fatty liver disease (NAFLD) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress and lipotoxicity. The present study aimed to elucidate the effect of Quaking 5 (QKI 5) as mediated by Sirtuin 1 (SIRT1) on triglyceride (TG) synthesis in the liver of an NAFLD mouse model. A high‑fat diet‑induced NAFLD model was established in mice, and mouse hepatocytes were isolated to characterize the effects of QKI 5 mediated by SIRT1 on TG synthesis in the liver. Body weight and liver wet weight were recorded. In addition, serum levels of total cholesterol, TG, alanine aminotransferase and aspartate aminotransferase were assessed using an automatic biochemistry analyzer. Hematoxylin and eosin staining was performed to observe the histological morphological alterations of the liver tissues. The concentration of SIRT1 in the serum was also detected. The NAFLD activity score (NAS) was used to evaluate disease severity. The synthesis of TGs in cells or tissues was determined, and the protein levels of SIRT1, QKI 5, peroxisome proliferator‑activated receptor (PPAR)α and Forkhead box protein O1 (FoxO1) were examined. The expression levels of SIRT1 or QKI 5, and the acetylation level of QKI 5 were decreased in the mouse model of NAFLD. QKI 5 was deacetylated by SIRT1, which contributed in suppressing the progression of NAFLD in the mice, and inhibiting TG synthesis in vivo and in vitro via the PPARα/FoxO1 signaling pathway. Taken together, the results of the present study demonstrated that SIRT1 deacetylated QKI 5, an RNA‑binding protein significantly affecting the synthesis of TG in the liver of the NAFLD mouse model. Furthermore, it activated transcription factor FOXO1 through post‑transcriptional regulation of the expression of PPARα and further inhibited the synthesis of TGs, thereby restraining the progression of NAFLD.

Background: EMT has a crucial effect on the progression and metastasis of tumors. This work will elucidate the role of miR-425 in EMT and the development of TNBC. Methods: The differential miRNA expression among non-tumor, para-tumor (adjacent tissue of tumor) and tumor tissues was analyzed. The luciferase activities of TGF-β1 3′UTR treated with miR-425 were determined. Then human breast cancer cell lines were treated with mimics or inhibitors of miR-425, and then the cell proliferation and migration, and invasion ability were assessed. The expression of TGF-β1 and markers of epithelial cells and mesenchymal cells were analyzed. The influences of miR-425 on the development of TNBC through inducing EMT by targeting the TGF-β1/SMAD3 signaling pathway in TNBC cell lines were investigated. Furthermore, xenograft mice were used to explore the potential roles of miR-425 on EMT and the development of TNBC in vivo. Results: Compared with non-tumor tissues, 9 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. The relative expression of miR-425 in tumor tissues was obviously much lower than that in para-tumor and non-tumor tissues. MiR-425 suppressed TGF-β1 expression, and further inhibited expression of mesenchymal cell markers, while it exerted effects on cell proliferation and migration of TNBC cell lines. Moreover, the agomir of miR-425 could protect against the development process in a murine TNBC xenograft model. Conclusions: Our results demonstrated that miR-425 targets TGF-β1, and was a crucial suppressor on EMT and the development of TNBC through inhibiting the TGF-β1/SMAD3 signaling pathway. This suggests that aiming at the TGF-β1/SMAD3 signaling pathway by enhancing relative miR-425 expression, is a feasible therapy strategy for TNBC.

A prospective method of treatment for cancer is to inhibit oncogene signaling pathways with microRNA (miRNA or miR). In the present study, whether the expression of STAT2, AdipoR1/AMPK/SIRT1 pathway of glioma is regulated by miR-3908 was explored. To confirm whether the predicted miR-3908 is matched with STAT2 and AdipoR1, 3'UTR luciferase activity of STAT2 and AdipoR1 was assessed. In the presence of the mimics or inhibitors of miR-3908, cell function of glioma cells, such as proliferation, growth, migration, invasion and apoptosis were analyzed. The expression of AdipoR1 and its downstream AMPK/SIRT1 pathway proteins or STAT2 were examined. Luciferase reporter analysis showed that miR-3908 directly target STAT2 and AdipoR1. miR-3908 suppressed expression of STAT2 or AdipoR1 and downregulated AdipoR1 pathway genes, including AMPK, p-AMPK and SIRT1. miR-3908 inhibited tumorigenicity, migration, growth and invasion in glioma cell lines U251 and U87 as well as increased apoptosis of these cells. The pathways related to tumorigenicity and tumor progression, STAT2 and AdipoR1/AMPK/SIRT1 could be restrained by miR-3908. In conclusion, restoration of miR-3908 expression induced suppression of cancer progression and glioblastoma tumorigenicity. The present study discovered novel tumorigenesis associated with miR-3908, which may represent a new target in treatment for glioblastoma.

The mechanisms of lipid raft regulation by microRNAs in breast cancer are not fully understood. This work focused on the evaluation and identification of miR-3908, which may be a potential biomarker related to the migration of breast cancer cells, and elucidates lipid-raft-regulating cell migration in breast cancer. To confirm the prediction that miR-3908 is matched with AdipoR1, we used 3’-UTR luciferase activity of AdipoR1 to assess this. Then, human breast cancer cell line MCF-7 was cultured in the absence or presence of the mimics or inhibitors of miR-3908, after which the biological functions of MCF-7 cells were analyzed. The protein expression of AdipoR1, AMPK, and SIRT-1 were examined. The interaction between AdipoR1 and Flotillin-1, or its effects on lipid rafts on regulating cell migration of MCF-7, was also investigated. AdipoR1 is a direct target of miR-3908. miR-3908 suppresses the expression of AdipoR1 and its downstream pathway genes, including AMPK, p-AMPK, and SIRT-1. miR-3908 enhances the process of breast cancer cell clonogenicity. miR-3908 exerts its effects on the proliferation and migration of MCF-7 cells, which are mediated by lipid rafts regulating AdipoR1’s ability to bind Flotillin-1. miR-3908 is a crucial mediator of the migration process in breast cancer cells. Lipid rafts regulate the interactions between AdipoR1 and Flotillin-1 and then the migration process associated with miR-3908 in MCF-7 cells. Our findings suggest that targeting miR-3908 and the lipid raft, may be a promising strategy for the treatment and prevention of breast cancer.

To investigate whether the mechanism by which a microRNA, miR-520a, suppresses the replication of hepatitis B virus (HBV) involves the regulation of the serine/threonine kinase (AKT) gene. The effects of miR-520a on the proliferation, mitotic index and apoptosis of the HBV-replicating human hepatocellular carcinoma cell line HepG2.2.15 were measured using standard laboratory methods including flow cytometry. The effects of miR-520a on HBV transcription and replication were assessed using methods including immunoassays and reverse transcription–polymerase chain reaction. The effect of small interfering RNA (siRNA) to AKT on the levels of AKT mRNA and protein were also evaluated. In HepG2.2.15 cells, miRNA-520a reduced HBV transcription and replication by reducing AKT levels. MiRNA-520a decreased cell proliferation and mitosis entry of cells and increased apoptosis in HepG2.2.15 cells. AKT levels were reduced significantly by its siRNA, which resulted in suppression of HBV replication in HepG2.2.15 cells. MiRNA-520a inhibited AKT gene expression and suppressed HBV transcription and replication. These findings suggest that miRNA-520a may be a novel target for the treatment of HBV infection because miRNA-520a reduced HepG2.2.15 cell survival and inhibited HBV replication associated with the AKT signalling pathway.