Transforming growth factor-β-induced miR?143 expression in regulation of non-small cell lung cancer cell viability and invasion capacity in vitro and in vivo

摘要

Altered expression of miRNAs contributes to development and progression of non-small cell lung cancer (NSCLC), while transforming growth factor-β (TGF-β) promotes NSCLC cell epithelial-mesenchymal transition. This study aimed to investigate the effects of TGF-β-induced miR?143 expression in regulation of NSCLC cell viability, invasion capacity in?vitro, and xenograft formation and growth in nude mice. NSCLC A549 cells treated with TGF-β were subjected to miRNA microarray analysis and miR?143 was selected for further study of tumor cell viability, wound healing, invasion capacity in?vitro, and tumor growth in nude mice. TGF-β treatment upregulated expression of 16 miRNAs and downregulated expression of 42 miRNAs in A549 cells. qRT-PCR and in?situ hybridization data showed that miR?143 was significantly downregulated in 24 NSCLC and lymph node metastatic tumor tissues, but upregulated by TGF-β treatment in A549 cells. In vitro experiments showed that miR?143 expression could significantly suppress NSCLC cell viability and invasion capacity, and nude mouse experiments confirmed the in?vitro data. Bioinformatic data predicted that Smad3, CD44 and K-Ras were the targeting genes of miR?143. TGF-β-induced miR?143 expression was associated with suppressed expression of Smad3, CD44, and K-Ras. This study sheds light on the role of TGF-β in upregulation of miR?143 and the role of miR?143 in NSCLC progression, indicating that the target of miR?143 expression could be further studied as a novel therapeutic strategy for future control of NSCLC.