RASSF1C regulates miR-33a and EMT marker gene expression in lung cancer cells.

Abstract

RASSF1C functions as an oncogene in lung cancer cells by stimulating proliferation and migration, and reducing apoptosis. Further, RASSF1C up-regulates important protein-coding and non-coding genes involved in lung cancer cell growth, including the stem cell self-renewal gene, piwil1, and small noncoding PIWI-interacting RNAs (piRNAs). In this article, we report the identification of microRNAs (miRNAs) that are modulated in lung cancer cells over-expressing RASSF1C. A lung cancer-specific miRNA PCR array screen was performed to identify RASSF1C target miRNA-coding genes using RNA isolated from the lung cancer cell line H1299 stably over-expressing RASSF1C and corresponding control. Several modulated miRNA genes were identified that are important in cancer cell proliferation and survival. Among the miRNAs down-regulated by RASSF1C is miRNA-33a-5p (miRNA-33a), which functions as a tumor suppressor in lung cancer cells. We validated that over-expression of RASSF1C down-regulates miR-33a expression and RASSF1C knockdown up-regulates miR-33a expression. We found that RASSF1C over-expression also increases β-catenin, vimentin, and snail protein levels in cells over-expressing miR-33a. In addition, we found that RASSF1C up-regulates the expression of ABCA1 mRNA which is a known target of miR-33a. Our findings suggest that RASSF1C may promote lung epithelial mesenchymal transition (EMT), resulting in the development of a lung cancer stem cell phenotype, progression, and metastasis, in part, through modulation of miR-33a expression. Our findings reveal a new mechanistic insight into how RASSF1C functions as an oncogene.

• Authors: Yousef G Amaar, Mark E Reeves
• Journal: Oncotarget (Oncotarget) Vol. 10 Issue 2 Pg. 123-132 (Jan 04 2019) ISSN: 1949-2553 [Electronic] United States
• PMID: 30719208 (Publication Type: Journal Article)