A regulatory loop involving miR-29c and Sp1 elevates the TGF-β1 mediated epithelial-to-mesenchymal transition in lung cancer

Specificity protein1 (Sp1) is required for TGF-beta-induced epithelial-to-mesenchymal transition (EMT) which has been demonstrated to aggravate the progression of cancer including lung cancer. microRNA-29c (miR-29c) is identified to inhibit EMT, but the correlation between miR-29c and Sp1 in human lung cancer remain incompletely clarified. Here, we confirmed decreased expression of miR-29c and enhanced expression of Sp1 in lung cancer tissues (n = 20) and found that Sp1 could be targeted and inhibited by miR-29c. Besides, the expression of miR-29c was down-regulated in high-metastatic lung cancer cell lines and TGF-beta 1treated cells. The inhibition of miR-29c or overexpression of Sp1 in 95C and A549 cells dramatically enhanced the cell migration and invasion, and also induced the decrease in the expression of epithelial markers, e.g. thyroid transcription factor 1 (TTF-1) and E-cadherin, together with an increase in mesenchymal markers including vimentin, a-smooth muscle actin (a-SMA), which could be restored by overexpression of miR-29c mimics during the TGF-beta-induced EMT. Moreover, dual-luciferase reporter assay was performed and the results indicated that miR-29c/Sp1 could form an autoregulatory loop with TGF-beta 1, which impaired TGFB1 transcription. Furthermore, miR-29c overexpression could abrogate the tumor progression and inhibit the Sp1/TGF-beta expressions in vivo, indicating that miR-29c could be a tumor suppressor and repress the Sp1/TGF-beta axis-induced EMT in lung cancer.