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

Altered expression of miRNAs contributes to development and progression of non-small cell lung cancer (NSCLC), while transforming growth factor-beta (TGF-beta) promotes NSCLC cell epithelial-mesenchymal transition. This study aimed to investigate the effects of TGF-13-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-beta 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-beta 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-beta 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-beta-induced miR-143 expression was associated with suppressed expression of Smad3, CD44, and K-Ras. This study sheds light on the role of TGF-43 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.