TGF-β1 regulating miR-205/miR-195 expression affects the TGF-β signal pathway by respectively targeting SMAD2/SMAD7

Abstract

Transforming growth factor-β (TGF-β) proteins are important cytokines in the occurrence and development of tumors. However, its neural functions in glioma are still not understood. In the present study, we evaluated the effects of TGF-β1 on glioma cell line U87. miR-205 and miR-195 were involved in TGF-β1 signaling pathway. Quantitative real-time PCR was used to detect miR-205 and miR-195 levels in human glioma tissue samples and U87 cells treated with different concentrations of TGF-β1. Enzyme-linked immunosorbent assay (ELISA) was performed to determine TGF-β1 in the glioma patients peripheral blood. In vitro, U87 cells were transfected with mimics or inhibitors of miR-205 and miR-195. SMAD proteins were assayed by western blotting. Luciferase assay and co-immunoprecipitation (Co-IP) were used to determine the relationships between miR-205 and SMAD2, miR-195 and SMAD7. Effects of miR-205 and miR-195 on glioma cell proliferation and invasion using colony forming and cell migration assays. It was shown that miR-205 was decreased in glioma tissue, but miR-195 and TGF-β1 was increased. In addition, TGF-β1 concentration was negatively correlated with miR-205 mRNA level, but positively correlated with miR-195 mRNA. In addition, miR-205 was downregulated and miR-195 was upregulated by TGF-β1 in a dose-dependent manner. miR-205 and miR-195 targeted and inhibited SMAD2 and SMAD7 expression, respectively, in U87. High expression of miR-205 but not miR-195 reduced SMAD2 and SMAD4 heteromer formation. In addition, it was also shown that miR-205 overexpression inhibited U87 proliferation and invasion efficiently. All the results suggested that miR-205 and miR-195 participated in the TGF-β1 signaling pathway and showed opposite effects in glioma. These findings contribute to the understanding of TGF-β1 function in glioma.

MiR‐195 and miR‐497 suppress tumorigenesis in lung cancer by inhibiting SMURF2‐induced TGF‐β receptor I ubiquitination

“…To identify the molecular mechanism of miR‐195 and miR‐497 in cancer, we selected the SMURF2 gene among the components of TGF‐β signaling as putative targets of miR‐195 and miR‐497 using prediction databases. In fact, many studies have reported that TGF‐β signaling promotes miR‐195 and miR‐497 expression (Chen et al , ; Duan and Chen, ; Song et al , ), and miR‐195/497 targets other proteins associated with TGF‐β signaling. We analyzed the expression of the SMURF2 gene in tumor and paired normal lung tissues from primary NSCLC patients in the NCBI GEO database (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21933) and lung cancer cell lines.…”

MicroRNA-195 Activates Hepatic Stellate Cells In Vitro by Targeting Smad7

“…With regard to HSCs, Sekiya found that, during primary HSCs (pHSCs) activation, miR-195 was downregulated on the 10th day compared with the 1st day, and miR-195 could decrease cyclin E expression and inhibit cell proliferation induced by interferon-B [ 21 ]. Duan and Chen demonstrated that miR-195 was upregulated by TGF- β 1 in a dose-dependent manner enhancing glioma cell invasion and proliferation in U87 cells [ 22 ]. Growing evidence has demonstrated that miR-195 plays an important role in the neoplastic disease; however, studies on the relationship between miR-195 and liver fibrosis are far from enough.…”

Role of MiR-205/PTEN in cisplatin-resistant esophageal squamous cell carcinoma

“…Furthermore, the results in this study showed that p-AKT was a downstream factor of PTEN. In addition to PTEN/p-AKT signaling pathway, TGF-β signaling pathway also regulates miRNA-205 expression [19], suggesting a possible interaction between different cell signaling pathways.…”