Abstract
Abstract Introduction: RASSF1C is emerging as an important oncoprotein in lung cancer cell growth. We have shown that RASSF1C promotes lung cancer cell proliferation and migration; and RASSF1C up-regulates important genes in lung cancer cell growth that include a stem cell self-renewal gene, piwi1 (hiwi). PIWI-like proteins are a subfamily of Argonaute proteins that interact with small PIWI-interacting RNA molecules (known as piRNAs that are 24-32 nucleotides long) to form complexes that regulate transcriptional and translational repression. This leads to inhibition of apoptosis, stimulation of cell division and proliferation, and down-regulation of cyclin inhibitors and tumor suppressors. Therefore, modulation of Piwil1-piRNA gene expression by RASSF1C suggests a potential role for RASSF1C in lung cancer stem cell development and progression. To further investigate our hypothesis, we carried out a global piRNA microarray screen to identify piRNAs that are modulated by RASSF1C in lung cancer cells. Method: A piRNA microarray screen was performed using the lung cancer cell line H1299 stably over-expressing RASSF1C (and controls). Total RNA was extracted from experimental and control cells and was submitted to Arraystar (Rockville, MD) for the piRNA microarray screen and data analysis. Results: The piRNA microarray screen identified several piRNAs that are regulated by RASSF1C and we have confirmed the expression of some of them in cell lines. The function of the piRNAs identified is yet to be determined. We have initiated studies to determine the function of some of the most up-regulated and down-regulated piRNA genes in lung cancer cells. We are also profiling the expression of these piRNAs in normal and lung tumor tissues. Conclusion: Several piRNAs are target genes of RASSF1C. Characterization of the function of these piRNAs may enhance our understanding of the role of RASSF1C in promoting lung cancer stem cell growth and progression. Linking a Rassf1c-Piwil1/piRNAs axis to lung cancer stem cell development and progression could possibly lead to discovery of new diagnostic and therapeutic targets for lung cancer. Citation Format: Yousef G. Amaar, Matthew Firek, Mark E. Reeves, Mark E. Reeves. RASSF1C modulation of Piwi-interacting RNAs (piRNAs) in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2146. doi:10.1158/1538-7445.AM2015-2146
Published Version
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