2026-06-14T03:43:16Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/253102025-12-18T13:00:43Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Vinchure, Omkar Suhas author Whittemore, Kurt author Kushwah, Deependra author Blasco, MA author Kulshreshtha, Ritu author Vinchure, Omkar Suhas author Whittemore, Kurt author Kushwah, Deependra author Kulshreshtha, Ritu author 2021-03 Glioblastoma (GBM) is the most aggressive cancer of central nervous system with worst patient outcome. Telomere maintenance is a crucial mechanism governing GBM initiation and progression making it an attractive target. microRNAs (miRNAs) have shown therapeutic potential in GBM. Earlier, we showed miR-490 is downregulated in GBM patients and plays a tumor suppressive role. Here, we show that miR-490 regulates telomere maintenance program in GBM by directly targeting Telomeric Repeat-binding Factor 2 (TERF2) of the shelterin complex, Tankyrase 2 (TNKS2) and Serine/Threonine-protein kinase, SMG1. Overexpression of miR-490 resulted in effects characteristic to hampered telomere maintenance via TERF2 inhibition. These include induction of telomere dysfunction-induced foci and global DNA damage (53BP1 foci), along with an increase in p-γH2AX levels. Further, it led to inhibition of telomere maintenance hallmarks via reduced stemness (SOX2 and SOX4 downregulation) and induction of senescence (H3K9me3 marks gain and SIRT1 downregulation). It also initiated downstream DNA damage response (DDR) leading to p53 pathway activation. Moreover, microarray data analysis highlighted an overlap between miR-490 expression and REST-inhibition responses in GBM. Thus, miR-490-mediated targeting of telomere maintenance could be therapeutically important in GBM. Cell Mol Life Sci . 2021 Mar;78(5):2299-2314. Cell Mol Life Sci 32970185 https://hdl.handle.net/20.500.12105/25310 DNA damage Glioblastoma REST TERF2 Telomeres miR-490 miR-490 suppresses telomere maintenance program and associated hallmarks in glioblastoma.