Abstract 1813: Depletion of PCAT1 in head and neck cancer cells limits tumor growth by regulating c-Myc, AKT1 and MAPK signalling pathways

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) represents one of the most common malignancies worldwide with a high mortality rate mainly due to lack of early detection markers, frequent metastasis and aggressive phenotype. Recently, long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancers. Up-regulation of prostate cancer-associated transcript 1 (PCAT1) in TCGA dataset of HNSCC was noted. In this study, we aimed to evaluate role of the PCAT1 in HNSCC. During validation, we observed up-regulation of PCAT1 in HNSCC patient samples and cell lines. siRNA mediated knock-down of PCAT1 significantly reduced cell proliferation, sphere formation and wound healing in HNSCC cell lines (JHU29 and Cal27). Mechanistic study revealed a significant down-regulation of c-Myc and AKT1 in both RNA and protein levels upon knockdown of PCAT1 in HNSCC cell lines. In-silico analysis suggested a significant positive correlation between PCAT1 and c-Myc or PCAT1 and AKT1 in HNSCC cell lines. Subsequently, we observed modulation of MAPK signalling by activation of p38 and apoptosis signal-regulating kinase 1 (ASK1) upon knockdown of PCAT1, and induction of apoptosis as evident of caspase 9 activation and PARP cleavage. Introduction of PCAT1 into HNSCC xenograft tumors displayed a reduction in tumor volume. Together our data demonstrated an important role of the PCAT1 in HNSCC progression and has potential as a therapeutic candidate. Citation Format: Subhayan Sur, Robert Steele, Ratna B. Ray. Depletion of PCAT1 in head and neck cancer cells limits tumor growth by regulating c-Myc, AKT1 and MAPK signalling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1813.