MicroRNA-148a reduces tumorigenesis and increases TRAIL-induced apoptosis in NSCLC.

Abstract

Nonsmall cell lung cancer (NSCLC) is one of the leading causes of death worldwide. TNF-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in malignant cells without inducing significant toxicity in normal cells. However, several carcinomas, including lung cancer, remain resistant to TRAIL. MicroRNAs (miRNAs) are small noncoding RNAs of ∼ 24 nt that block mRNA translation and/or negatively regulate its stability. They are often aberrantly expressed in cancer and have been implicated in increasing susceptibility or resistance to TRAIL-induced apoptosis by inhibiting key functional proteins. Here we show that miR-148a is down-regulated in cells with acquired TRAIL-resistance compared with TRAIL-sensitive cells. Enforced expression of miR-148a sensitized cells to TRAIL and reduced lung tumorigenesis in vitro and in vivo through the down-modulation of matrix metalloproteinase 15 (MMP15) and Rho-associated kinase 1 (ROCK1). These findings suggest that miR-148a acts as a tumor suppressor and might have therapeutic application in the treatment of NSCLC.

• Authors: Pooja Joshi, Young-Jun Jeon, Alessandro Laganà, Justin Middleton, Paola Secchiero, Michela Garofalo, Carlo M Croce
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 28 Pg. 8650-5 (Jul 14 2015) ISSN: 1091-6490 [Electronic] United States
• PMID: 26124099 (Publication Type: Journal Article)

Chemical References

• MIRN148 microRNA, human
• MicroRNAs
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human

Topics

• Apoptosis (physiology)
• Carcinogenesis
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Line, Tumor
• DNA Methylation
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• MicroRNAs (physiology)
• TNF-Related Apoptosis-Inducing Ligand (physiology)