MicroRNA-183 promotes migration and invasion of CD133+/CD326+ lung adenocarcinoma initiating cells via PTPN4 inhibition
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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.
KeywordsmiR-183 PTPN4 CD133/CD326 Cancer stem-like cells Tumor-initiating cells
This work was supported by the National Natural Science Foundation of China (NSFC81201682).
Compliance with ethical standards
The care and use of mice was performed in accordance with ethical guidelines of Southwest Medical University.
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