MicroRNA-183 promotes migration and invasion of CD133+/CD326+ lung adenocarcinoma initiating cells via PTPN4 inhibition

• Published in: Tumor biology Vol. 37; no. 8; pp. 11289 - 11297
• Main Authors: Zhu, Conghui, Deng, Xi, Wu, Jingbo, Zhang, Jianwen, Yang, Hongru, Fu, Shaozhi, Zhang, Yan, Han, Yunwei, Zou, Yuanmei, Chen, Zhengtang, Lin, Sheng
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-08-2016
• Subjects: AC133 Antigen; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Animals; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Cell Line, Tumor; Cell Movement; Epithelial Cell Adhesion Molecule; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic - genetics; Heterografts; Humans; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mice; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Neoplasm Invasiveness - genetics; Neoplastic Stem Cells - pathology; Original Article; Protein Tyrosine Phosphatase, Non-Receptor Type 4 - biosynthesis; Real-Time Polymerase Chain Reaction; Tumor-initiating cells; miR-183; CD133/CD326; Cancer stem-like cells; PTPN4
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-016-4955-8

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide and is a leading cause of lung cancer mortality due to early stage metastases. Cancer stem-like cells (CSLCs) or tumor-initiating cells (TICs) are rare subpopulation cells that are responsible for maintaining tumor growth and invasion leading to recurrence and metastasis. Previous studies revealed that miR-183 can mediate the invasiveness and growth of NSCLC. However, the exact role of miR-183 in regulating the biological behavior of CSLCs in NSCLC remains unclear. In the present study, we explored the regulation of protein tyrosine phosphatase non-receptor type 4 (PTPN4) by miR-183 in vitro using luciferase reporter assays, and we further analyzed the effects of miR-183 on the invasiveness of CSLCs in vitro and in vivo using transwell and bioluminescence assays. Following our finding that miR-183 binds to PTPN4 messenger RNA (mRNA) to prevent its translation through the 3′-untranslated region (UTR), we found that overexpression of miR-183 in CSLCs decreased PTPN4 protein levels while inhibition of miR-183 increased PTPN4 protein levels. The suppression of PTPN4 levels in CSLCs by miR-183 paralleled with a significant promotion in their motility in vitro and in vivo, while anti-sense miR-183 increased PTPN4 levels in CSLCs, which paralleled with a significant decrease in their invasiveness. Furthermore, correlation analysis between miR-183 and PTPN4 in clinical samples demonstrated a statistically significant inverse correlation between PTPN4 mRNA levels and miR-183. In brief, our data indicate that miR-183 plays a pro-invasive role by inverse regulation of PTPN4, and this axis may be a new therapeutic target for suppressing the metastatic capability of CSLCs in NSCLC.