CSIG-36. INVOLVEMENT OF microRNAs 221/222-3p IN THE REGULATION OF PROGRAMMED CELL DEATH 10 (PDCD10) GENE IN GLIOBLASTOMA. (5th November 2018)

• Record Type: Journal Article
• Authors: Malik, Nargis; Chattopadhyay, Parthaprasad; Sarkar, Chitra; Suri, Ashish; Sinha, Subrata; Chosdol, Kunzang
• Is Part Of: Neuro-oncology. Volume 20(2018)Supplement 6
• Page Start: vi51
• Page End: vi51
• Publication Date: 2018-11-05
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy148.202
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: INTRODUCTION: FAT1 gene is localized at chromosome 4q35.2 encoding a 506KDa. Here in our study we are characterizing the role of FAT1 in primary brain tumors. MiR-221-3p/222-3p reported to have oncogenic role and targets tumor suppressors (e.g. PDCD10, PTEN, PUMA etc.) in many cancers including GBM. Here, we have analyzed the role of FAT1 gene in the regulation of miRNAs in GBM. METHODOLOGY: In-silico analysis of miR targets was done by target prediction software miRDB, TargetScan, miRTarBase. FAT1 knockdown was done using FAT1 specific siRNA and mRNA expression analysis done by gene specific primers and for miR-221/222-3p using LNA-primers in GBM cell lines (U87MG, U373MG, A172 and LN229). Expression and Spearman correlation analysis of FAT1 and miR-221-3p was done in GBM tumor samples (n=30). RESULTS: We have observed increased expression of FAT1 and miRNAs (miR221-3p/miR222-3p) in GBM cell lines (U87MG, U373MG, A172 & LN229). On FAT1 knockdown, by siFAT1 we observed significantly reduced expression of miR-221/222-3p. In-silico analysis identified, TIMP3, PDCD10, PUMA and PTEN as potential targets of miR-221/222-3p. Furthermore, FAT1 knocked-down cells showed significantly augmented expression of PDCD10 in all studied glioma cell lines. In order to validate our in-vitro observation and its clinical relevance, we have done expression and correlation study in GBM tumor samples. We observed significant positive spearman correlation between FAT1 and miR-221-3p (r=0.5669, p≤0.0011) and negative correlation of FAT1 with PDCD10 (r= -0.3492, p≤0.0585), ) and miR-221-3p with PDCD10 (r=0.526, p≤0.0028). These results suggest that FAT1 expression positively regulates the expression of miR-221-3p leading to downregulation of miR 221-3p target (PDCD10) in GBM cell lines and GBM tumors. CONCLUSION: Taken together our in-vitro and GBM tumor data for the first time suggesting FAT1 to be a novel molecule regulating the expression of miRNA in GBM and FAT1 may emerge as a target for therapeutic intervention.