Abstract 774: Regulation of autophagy and epigenetic modulator micro RNA by transient receptor potential melastatin 7 (TRPM7) channel in glioma

Abstract

Abstract High grade malignant gliomas are devastating, uniformly fatal cancers for which no effective therapies currently exist. Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. We have reported that TRPM7 channels, a subfamily member of the transient receptor potential (TRP), regulate glioma stem cell (GSC) growth/proliferation through STAT3 and Notch signaling pathways. Autophagy is a catabolic process that occurs during both physiological and pathological process which has been reported to have dual roles, functioning either as a tumor-suppressor or tumor-promoter in cancer, including glioma. In addition, because of the limited success of the traditional treatment in prolonging the overall survival in GBM patients, epigenetics and epigenetic modulators have been attracting an increasing amount of attention for their influence in many aspects of cancer. microRNAs (miRNA), which can be considered as epigenetic effectors, reversibly regulate transcription through binding to complementary sequences of mRNA and silencing its translation into proteins. Therefore, we first determined the role of autophagy process in regulating glioma by TRPM7 using real time RT2 Profile PCR arrays (SABioscience, PAHS-084Z). We found that ATG16L1, ATG9A, CDKN1B, CLN3, CXCR4, and RGS19 were upregulated in response to TRPM7 silencing with the fold change greater than 1.6 using the A172 cell line of human glioma. The gene changes were further validated in other three glioma cell lines U87MG, U373MG and SNB19, which demonstrated different glioma tumorigenicity. miroRNA microarray analysis were then were performed upon TRPM7 silencing in A172 cells (www.LCsciences.com). In-depth data analysis from miRNA microarray data showed a list of 16 downregulated and 10 upregulated miRNA whose transcripts are statistically significant with fold change greater than 2 by TRPM7 knock-down. Among these, the micro RNA of hsa-miR-26b-5p, has-miR4530, and has-miR-28-5p have shown to exert crucial influence on tumor growth and migration by modulating AKT, ERK and IGF-1 signaling pathways. Stem-loop RT-qPCR were then used to detect and quantify miRNAs identified in miRNA microarray data from U87MG, U373MG and SNB19 cell lines. Our data indicate that autophagy effects serve as tumor suppressors in gliomagenesis and are reversely regulated by TRPM7; while hsa-miR-26b-5p, has-miR4530, and has-miR-28-5p are regulated by TRPM7 and participate in glioma progression. Citation Format: Mingli Liu. Regulation of autophagy and epigenetic modulator micro RNA by transient receptor potential melastatin 7 (TRPM7) channel in glioma [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 774.