Research Papers:

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

Yousef G. Amaar _ and Mark E. Reeves

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Oncotarget. 2019; 10:123-132. https://doi.org/10.18632/oncotarget.26498

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Yousef G. Amaar1 and Mark E. Reeves1,2

1Surgical Oncology Laboratory, Loma Linda VA Medical Center, Loma Linda, CA, USA

2Loma Linda University Cancer Center, Loma Linda, CA, USA

Correspondence to:

Yousef G. Amaar, email: [email protected]

Keywords: lung cancer; RASSF1C; miR-33a; EMT

Received: July 18, 2018     Accepted: December 13, 2018     Published: January 04, 2019


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.

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