No abstract

TGFβR1 plays an important role in TGF-β signaling transduction and serves as a tumor suppressor. Our previous studies show that reduced expression of TGFβR1 is common in non-small cell lung cancer (NSCLC) and TGFβR1 variants confer risk of NSCLC. However, the epigenetic mechanisms underlying the role of TGFβR1 in NSCLC carcinogenesis are still elusive. We investigated the function and regulation of TGF-β signaling-based miRNAs in NSCLC. Computational algorithms predicted that the 3'-untranslated region (3'-UTR) of TGFβR1 is a target of miR-142-3p. Here a luciferase reporter assay confirmed that miR-142-3p can directly bind to 3'-UTR of TGFβR1. Overexpression of miR-142-3p in NSCLC A549 cells suppressed expression of TGFβR1 mRNA and protein, while knockdown of endogenous miR-142-3p led to increased expression of TGFβR1. On TGF-β1 stimulation, stable overexpression of miR-142-3p attenuated phosphorylation of SMAD3, an indispensable downstream effector in canonical TGF-β/Smad signaling, via repression of TGFβR1 in A549 cells. Furthermore, miR-142-3p-mediated down-regulation of TGFβR1 weakened TGF-β-induced growth inhibition effect, and this effect was reversed by stable knockdown of endogenous miR-142-3p in A549 cells. In NSCLC tissues, miR-142-3p expression was increased and inversely correlated with TGFβR1 expression. These data demonstrate that miR-142-3p influences the proliferation of NSCLC cells through repression of TGFβR1.

MicroRNAs are novel small noncoding RNA molecules that regulate gene expression at the post-transcriptional level. Compelling evidence reveals that there is a causative link between microRNAs deregulation and cancer development and progression. The present study aims to explore the function of miR-206 in the proliferation, apoptosis, motility, and invasion of nonsmall cell lung cancer. Using real-time PCR, we detected the miR-206 expression of normal lung tissues, tumor tissues, human normal bronchial epithelial cell line, and six lung cancer cell lines (LCCLs). Then, we evaluated the role of miR-206 in cell proliferation, apoptosis, and invasion using Cell Counting Kit-8 assay, Annexin-V/FITC assay, wound healing, and Transwell assay in LCCLs. As a result, miR-206 expression level was lower in high metastasis tumors and 95D than low metastasis tumors and normal lung tissues as well as other LCCLs. After miR-206 was upregulated in LCCLs, cell proliferation was notably attenuated and apoptosis was significantly increased. Furthermore, overexpression of miR-206 inhibited migration and invasion of lung cancer cells. In conclusion, our data suggest that expression level of miR-206 was inversely correlated with metastatic potential of lung cancer. Anat Rec, 294:88-92, 2011. V V C 2010 Wiley-Liss, Inc.