MicroRNA-193a-3p and -5p suppress the metastasis of human non-small-cell lung cancer by downregulating the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway.

Abstract

The metastatic cascade is a complex and multistep process with many potential barriers. Recent evidence has shown that microRNAs (miRNAs) are involved in carcinogenesis and tumor progression in non-small-cell lung cancer (NSCLC). In this study, by comparing the miRNA expression profiles of SPC-A-1sci (high metastatic) and SPC-A-1 (weakly metastatic) cells, we demonstrated that the downregulation and function of miR-193a-3p and miR-193a-5p in NSCLC metastasis and the expression of these miRNAs was suppressed in NSCLC compared with corresponding non-tumorous tissues. Decreased miR-193a-3p/5p expression was significantly associated with tumor node metastasis (TNM) and lymph node metastasis. Furthermore, functional assays showed that the overexpression of miR-193a-3p/5p inhibited NSCLC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and lung metastasis formation in vivo. In addition, we discovered that ERBB4 and S6K2 were the direct targets of miR-193a-3p and that PIK3R3 and mTOR were the direct targets of miR-193a-5p in NSCLC. We also observed that miR-193a-3p/5p could inactivate the AKT/mTOR signaling pathway. Thus, miR-193a-3p/5p functions as a tumor suppressor and has an important role in NSCLC metastasis through ERBB signaling pathway.

• Authors: T Yu, J Li, M Yan, L Liu, H Lin, F Zhao, L Sun, Y Zhang, Y Cui, F Zhang, J Li, X He, M Yao
• Journal: Oncogene (Oncogene) Vol. 34 Issue 4 Pg. 413-23 (Jan 22 2015) ISSN: 1476-5594 [Electronic] England
• PMID: 24469061 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN193 microRNA, human
• MicroRNAs
• MTOR protein, human
• PIK3R3 protein, human
• ERBB4 protein, human
• Receptor, ErbB-4
• Ribosomal Protein S6 Kinases
• TOR Serine-Threonine Kinases

Topics

• Animals
• Carcinoma, Non-Small-Cell Lung (genetics, pathology, secondary)
• Cell Line, Tumor
• Down-Regulation
• Epithelial-Mesenchymal Transition
• Humans
• Lung Neoplasms (genetics, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• MicroRNAs (physiology)
• Neoplasm Invasiveness
• Neoplasm Metastasis (prevention & control)
• Phosphatidylinositol 3-Kinases (physiology)
• Receptor, ErbB-4 (physiology)
• Ribosomal Protein S6 Kinases (physiology)
• Signal Transduction (physiology)
• TOR Serine-Threonine Kinases (physiology)