SUN-009 N(6)-Methyladenosine Reader HNRNPA2B1 Regulates Tamoxifen-Sensitivity in Breast Cancer Cells

Abstract

The RNA methylation reader Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2B1) is a reader of the N(6)-methyladenosine (m6A) mark in mRNA and primary-miRNAs, HNRNPA2B1 interacts directly with DGCR8 in the DROSHA complex to promote processing of pri-miRNAs to precursor-miRNAs (pre-miRNAs). We report that HNRNPA2B1 expression is higher in tamoxifen-resistant, estrogen receptor α (ERα)+ LCC9 cells derived from tamoxifen-sensitive, ERα+ MCF-7 cells. To examine how increased expression of HNRNPA2B1 affects miRNA expression, we transiently overexpressed HNRNPA2B1 in MCF-7 cells for whole genome expression profiling (RNA seq). We identified 148 miRNAs upregulated and 88 downregulated 48 h after transfection and 177 miRNAs upregulated and 172 downregulated 72 h after transfection. MetaCore Gene Ontology was used to identify pathways downstream of miRNAs altered by HNRNPA2B1. Stable overexpression (~5.4-fold increase) of HNRNPA2B1 in MCF-7 cells (~5.4-fold increase) blocked growth inhibition by fulvestrant. siHNRNPA2B1 transfection enhanced tamoxifen and fulvestrant inhibition of MCF-7 cell viability. Results suggest a role for increased HNRNPA2B1 expression in tamoxifen-resistance.