MicroRNA-21 (miR-21) expression promotes growth, metastasis, and chemo- or radioresistance in non-small cell lung cancer cells by targeting PTEN

Abstract

MicroRNAs (miRNAs) regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. In our previous study, we have shown that expression of serum microRNA (miR)-21 is correlated with TNM stage and lymph node metastasis and might be an independent prognostic factor for NSCLC patients. However, the roles of miR-21 overexpression in NSCLC development are still unclear. The purpose of this study is to investigate the effect of miR-21 and determine whether miR-21 can be a therapeutic target for human NSCLC. Taqman real-time quantitative RT-PCR assay was performed to detect miR-21 expression in NSCLC cell lines and tissues. Next, the effects of miR-21 expression on NSCLC cell characteristics including growth, invasion, and chemo- or radioresistance were also determined. Results showed that miR-21 is commonly upregulated in NSCLC cell lines and tissues with important functional consequences. In addition, we found that anti-miR-21 could significantly inhibit growth, migration and invasion, and reverse chemo- or radioresistance of NSCLC cells, while miR-21 mimics could increase growth, promote migration and invasion, and enhance chemo- or radioresistance of NSCLC cells. Meanwhile, miR-21 mimics could inhibit expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3'-untranslated region (UTR)-based reporter construct in A549 cells, while anti-miR-21 could increase expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3'-UTR-based reporter construct in A549 cells. Furthermore, overexpression of PTEN could mimic the same effects of anti-miR-21 in NSCLC cells, and siRNA-mediated downregulation of PTEN could rescue the effects on NSCLC cells induced by anti-miR-21. Taken together, these results provide evidence to show the promotion role of miR-21 in NSCLC development through modulation of the PTEN signaling pathway.

MiR-21 Upregulation Induced by Promoter Zone Histone Acetylation is Associated with Chemoresistance to Gemcitabine and Enhanced Malignancy of Pancreatic Cancer Cells

“…microRNA-21 has been suggested to function as an oncogene because it is overexpressed in many types of malignancy such as lung cancer (Liu et al, 2013), ovarian cancer (Iorio et al, 2007), colon cancer (Slaby et al, 2007), gastric cancer (Chan et al, 2008) and esophageal squamous cell carcinoma (Hiyoshi et al, 2009). Particularly, it had a high expression in the more aggressive PDAC cell and tissue samples .…”

MicroRNAs and Their Impact on Radiotherapy for Cancer

“…Furthermore, PTEN is a known target of miR-21. Mimics of miR-21 inhibited PTEN expression and enhanced radioresistance in non-small cell lung cancer cells (59), and inhibition of miR-21 increased radiosensitivity via PTEN in esophageal cancer (60). An additional miRNA that potentially targets PTEN is miR-205.…”

Over-Expression of miR-21 and Lower PTEN Levels in Wilms’ Tumor with Aggressive Behavior

“…Meng et al (2006Meng et al ( , 2007 first demonstrated that miR-21 can regulate the tumor suppressor gene PTEN in bile duct carcinoma and hepatocellular carcinoma cells and promote the invasion and migration of tumor cells, which showed that PTEN is a latent target gene of miR-21. Later PTEN was proved to be a target gene of miR-21 in other tumors (Zhang et al 2010;Li et al 2013b;Liu et al 2013 Our study determined a significantly negative correlation between the expression of miR-21 and the PTEN protein in WT tissues. The high miR-21 level had a significant correlation with age (> 24 months), UH tumor type and lymphatic metastasis; the low PTEN protein level was significantly associated with age (> 24 months), late clinical stage and UH tumor type.…”