P2.02-012 The Epigenetic Role of LSD1+8a in Small Cell Lung Cancer

Abstract

Small cell lung cancer (SCLC) is a neuroendocrine tumor which account for 15% of all lung cancers. SCLC is characterized by rapid progression which led metastasis to distant organs and represented poor prognosis. Although there were various molecular targeted therapies in SCLC that were already under investigation, results have been disappointing. The focus on biological pathways has recently shifted from genetic to epigenetic regulations. Histone methylation is one of the epigenetic mechanisms which has pivotal role in gene expression, cell cycle and differentiation. Lysine-specific demethylase 1 (LSD1)/KDM1 is a histone modifier that is expressed in certain human cancers including SCLC. LSD1+8a is one of the isoform of LSD1 that was reported to be restricted in neural tissues and it plays critical role in neuronal differentiation. The aim of this study is to elucidate the epigenetic role of LSD1+8a in SCLC. The expression of LSD1 and LSD1+8a mRNAs were analyzed by qPCR in several cancer cell lines. Neuroendocrine markers were detected by qPCR in several SCLC cell lines. The Pearson correlation test was performed to investigate the correlation between LSD1+8a and neuroendocrine markers. siRNA against specific to exon 8a was designed and knockdown LSD1+8a isoform specifically. Cell proliferation assays following knockdown of LSD1+8a were performed in LSD1+8a expressed SCLC cell lines. LSD1 mRNA was expressed in majority of SCLC cell lines, interestingly LSD1+8a mRNA was detected in small subset of SCLC cell lines. There were positive correlations of LSD1+8a and neuroendocrine marker genes such as chromogranin A (CHGA), enolase2 (ENO2), neural cell adhesion molecule (NCAM) and synaptophysin (SYP) in human cancer cell lines. The suppression of LSD1+8a by siRNA drove to decrease expression of neuroendocrine marker genes in SCLC and inhibited cell proliferation in LSD1+8a expressed cell. LSD1+8a could play an important role in SCLC.