LncRNA MAGI2-AS3 inhibits bladder cancer progression by targeting the miR-31-5p/TNS1 axis.

In this study, we performed bioinformatics analysis to identify the competing endogenous RNAs (ceRNAs) that regulate bladder cancer (BCa) progression. RNA-sequencing data analysis identified 2451 differentially expressed mRNAs, 174 differentially expressed lncRNAs, and 186 microRNAs (miRNAs) in BCa tissues (n=414) compared to the normal urothelial tissues (n=19) from the TGCA database. CeRNA network analysis of the differentially expressed lncRNAs and mRNAs showed strong positive correlation between lncRNA MAGI2-AS3 and Tensin 1 (TNS1) mRNA in BCa tissues. Bioinformatics analysis also showed that both MAGI2-AS3 and TNS1 mRNA sequences contain miR-31-5p binding sites. Furthermore, we observed significantly lower MAGI2-AS3 and TNS1 mRNA expression and higher miR-31-5p expression in the BCa tissues and cell lines (T24 and J82) compared with their corresponding controls. Functional and biochemical experiments in BCa cell lines including luciferase reporter assays showed that MAGI2-AS3 upregulated TNS1 by sponging miR-31-5p. Transwell assays showed that the MAGI2-AS3/miR-31-5p/TNS1 axis regulated migration and invasion ability of BCa cell lines. Moreover, immunohistochemical staining of paired BCa and normal urothelial tissues showed that low expression of TNS1 correlated with advanced tumor (T) stages and lymph node metastasis in BCa. In conclusion, our study demonstrates that the MAGI2-AS3/miR-31-5p/TNS1 axis regulates BCa progression.

Tensin1 expression and function in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) constitutes a major cause of morbidity and mortality. Genome wide association studies have shown significant associations between airflow obstruction or COPD with a non-synonymous SNP in the TNS1 gene, which encodes tensin1. However, the expression, cellular distribution and function of tensin1 in human airway tissue and cells are unknown. We therefore examined these characteristics in tissue and cells from controls and people with COPD or asthma. Airway tissue was immunostained for tensin1. Tensin1 expression in cultured human airway smooth muscle cells (HASMCs) was evaluated using qRT-PCR, western blotting and immunofluorescent staining. siRNAs were used to downregulate tensin1 expression. Tensin1 expression was increased in the airway smooth muscle and lamina propria in COPD tissue, but not asthma, when compared to controls. Tensin1 was expressed in HASMCs and upregulated by TGFß1. TGFß1 and fibronectin increased the localisation of tensin1 to fibrillar adhesions. Tensin1 and α-smooth muscle actin (αSMA) were strongly co-localised, and tensin1 depletion in HASMCs attenuated both αSMA expression and contraction of collagen gels. In summary, tensin1 expression is increased in COPD airways, and may promote airway obstruction by enhancing the expression of contractile proteins and their localisation to stress fibres in HASMCs.

Tensin-3 Regulates Integrin-Mediated Proliferation and Differentiation of Tonsil-Derived Mesenchymal Stem Cells.

Human palatine tonsils are potential tissue source of multipotent mesenchymal stem cells (MSCs). The proliferation rate of palatine tonsil-derived MSCs (TMSCs) is far higher than that of bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs (ADSCs). In our previous study, we had found through DNA microarray analysis that tensin-3 (TNS3), a type of focal adhesion protein, was more highly expressed in TMSCs than in both BMSCs and ADSCs. Here, the role of TNS3 in TMSCs and its relationship with integrin were investigated. TNS3 expression was significantly elevated in TMSCs than in other cell types. Cell growth curves revealed a significant decrease in the proliferation and migration of TMSCs treated with siRNA for TNS3 (siTNS3). siTNS3 treatment upregulated p16 and p21 levels and downregulated SOX2 expression and focal adhesion kinase, protein kinase B, and c-Jun N-terminal kinase phosphorylation. siTNS3 transfection significantly reduced adipogenic differentiation of TMSCs and slightly decreased osteogenic and chondrogenic differentiation. Furthermore, TNS3 inhibition reduced active integrin beta-1 (ITGß1) expression, while total ITGß1 expression was not affected. Inhibition of ITGß1 expression in TMSCs by siRNA showed similar results observed in TNS3 inhibition. Thus, TNS3 may play an important role in TMSC proliferation and differentiation by regulating active ITGß1 expression.