MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma
Journal
PLoS ONE
Journal Volume
9
Journal Issue
5
Date Issued
2014
Author(s)
Abstract
Non-small cell lung cancers (NSCLCs) cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R), TGF-beta receptor type-1 (TGFBR1), and epidermal growth factor receptor (EGFR), are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer. ? 2014 Wang et al.
SDGs
Other Subjects
epidermal growth factor receptor; membrane receptor; microRNA; microRNA 133a; protein kinase B; somatomedin C receptor; transforming growth factor beta receptor 1; unclassified drug; cell surface receptor; microRNA; MIRN133 microRNA, human; oncoprotein; protein kinase B; animal experiment; animal model; article; bronchus mucosa; cancer cell line; cancer growth; cancer inhibition; cancer prognosis; cancer survival; cell growth; cell invasion; controlled study; correlation analysis; epithelium cell; gene expression; human; human cell; human tissue; lung non small cell cancer; major clinical study; mouse; nonhuman; protein expression; signal transduction; survival rate; survival time; tumor invasion; Carcinoma, Non-Small-Cell Lung; cell proliferation; down regulation; gene silencing; genetics; Lung Neoplasms; metabolism; metastasis; pathology; prognosis; tumor cell line; tumor invasion; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Gene Knockdown Techniques; Humans; Lung Neoplasms; MicroRNAs; Neoplasm Invasiveness; Neoplasm Metastasis; Oncogene Proteins; Prognosis; Proto-Oncogene Proteins c-akt; Receptors, Cell Surface; Signal Transduction
Type
journal article