Abstract 984: LncRNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs

Abstract

Abstract Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data of gastric cancer and integrating analyses, we screened out LINC00668, whose expression is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed the proliferation both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). Moreover, we also found that LINC00668 plays a key role in G0/G1 arrest, and further demonstrated that LINC00668 was associated with PRC2 and that this association was required for the epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of gastric cancer cell cycle. To our knowledge, this is the first report showed that the role and molecular mechanism of LINC00668 in cancer. Together, our results suggest that E2F1-regulated LINC00668, as a cell cycle regulator, enriches a mechanistic link between lncRNA and E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer. Key words: E2F1; LINC00668; cell cycle; proliferation; gastric cancer Acknowledgements: The work was partly supported by the National 973 Basic Research Program of China (Grant No. 2013CB911300) grants from the National Natural Science Foundation of China (Grant No. 81272469, 81502071 and 81572928) and the clinical special project for Natural Science Foundation of Jiangsu Province (Grant No. BL2012016), and the grant from Nanjing 12th Five-Year key Scientific Project of medicine to Dr. Jinfei Chen. Citation Format: Jinfei Chen. LncRNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 984.