Abstract 2080: Role of differentially expressed micro RNAs in non-WNT, non-SHH medulloblastoma

Abstract

Abstract Medulloblastoma is a common malignant brain tumor in children. It has four distinct molecular subgroups namely WNT, SHH, Group 3 and Group 4. The molecular subgroups differ in their clinical characteristics including age, incidence of metastasis and survival. Group 3 and Group 4 medulloblastomas have overlapping gene expression profile but are distinct in their clinical behavior. Group 3 medulloblastomas have the worst overall survival rates whereas Group 4 medulloblastomas have intermediate survival. Group 3 and Group 4 tumors are not associated with any known signaling pathway and due to their overlapping expression profiles it is often difficult to accurately identify the subgroup, which is very crucial for the appropriate treatment design. MiR-592, located in the intronic region of GRM8 gene, is over expressed in Group 4 medulloblastoma along with its host gene, thus acting as a good marker for Group 4 tumors. MiR-204, on the other hand is expressed from the 6th intron of TRPM3 gene and expressed in some Group 3 and majority of Group 4 medulloblastomas. In order to delineate the role of miR-592 and miR-204 in medulloblastoma biology, effect of expression of these microRNAs on medulloblastoma cell growth and behavior were investigated. The micro RNAs were expressed in a lentiviral mediated inducible manner in Group 3 medulloblastoma cell lines D283, D425 and D341 and their effects on cell proliferation, anchorage-independent growth and invasion potential were studied. MiR-592 expression had marginal effects on the anchorage independent growth potential and the tumorigenic potential of the Group 3 cell line where as miR-204 expression led to significant decrease in the anchorage independent growth, tumorigenic potential, as well as invasion potential of the medulloblastoma cell lines. Further in order to decipher the molecular mechanisms underlying these micro RNA mediated effects, RNA-sequencing analysis of miR-592 and miR-204 expressing medulloblastoma cells were performed to identify genes that are differentially expressed upon micro RNA expression. The results helped us to identify the molecular pathways that are being affected by the micro RNA expression and how they affect the malignant behavior of medulloblastoma cells. Citation Format: Raikamal Paul, Rakesh Jalali, Epari Sridhar, Aliasagar Moiyadi, Neelam Shirsat. Role of differentially expressed micro RNAs in non-WNT, non-SHH medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2080.