MicroRNA-300 targets hypoxia inducible factor-3 alpha to inhibit tumorigenesis of human non-small cell lung cancer.

Abstract

Non-small cell lung cancer (NSCLC) is one of the most deadly human cancers. MicroRNA-300 acts as both tumor promoter and suppressor in different types of cancer. Here, we try to identify the function of microRNA-300 in human NSCLC. We compared MicroRNA-300 levels between tumor tissues versus paired adjacent non-tumor lung tissues from NSCLC patients, and in NSCLC versus normal lung cell lines. Effects of microRNA-300 on cell proliferation, invasion and migration were examined in vitro, and on tumor growth in vivo using a xenograft mouse model. Potential mRNA targets of microRNA-300 were predicted and underlying mechanism was explored. MicroRNA-300 expression was lower in both NSCLC tissues and cell lines. Overexpression of microRNA-300 inhibited proliferation, invasion and migration of NSCLC cells in vitro, and tumor growth in vivo. MicroRNA-300 could directly bind to the 3'-UTR of hypoxia inducible factor-3 alpha (HIF3α) mRNA, and inhibit both its mRNA and protein expressions. Restoring HIF3α expression could rescue the inhibitory effects of microRNA-300 on tumorigenesis of NSCLC both in vitro and in vivo. MicroRNA-300 is a tumor suppressor microRNA in NSCLC by downregulating HIF3α expression. Both microRNA-300 and HIF3α may serve as potential therapeutic targets in NSCLC treatment.

• Authors: Y Zhang, Y Guo, C Yang, S Zhang, X Zhu, L Cao, W Nie, H Yu
• Journal: Neoplasma (Neoplasma) 2017 Vol. 64 Issue 4 Pg. 554-562 ISSN: 0028-2685 [Print] Slovakia
• PMID: 28485161 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• Basic Helix-Loop-Helix Transcription Factors
• HIF3A protein, human
• MIRN300 microRNA, human
• MicroRNAs
• Repressor Proteins

Topics

• Animals
• Apoptosis Regulatory Proteins
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Carcinogenesis
• Carcinoma, Non-Small-Cell Lung (genetics, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• Lung Neoplasms (genetics, pathology)
• Mice
• MicroRNAs (genetics)
• Repressor Proteins
• Xenograft Model Antitumor Assays