PMID- 33090636 OWN - NLM STAT- MEDLINE DCOM- 20210301 LR - 20231213 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 112 IP - 2 DP - 2021 Feb TI - Steroid receptor coactivator-1 enhances the stemness of glioblastoma by activating long noncoding RNA XIST/miR-152/KLF4 pathway. PG - 604-618 LID - 10.1111/cas.14685 [doi] AB - Glioblastoma (GBM) recurrence is attributed to the presence of therapy-resistant glioblastoma stem cells. Steroid receptor coactivator-1 (SRC-1) acts as an oncogenic regulator in many human tumors. The relationship between SRC-1 and GBM has not yet been studied. Herein, we investigate the role of SRC-1 in GBM. In this study, we found that SRC-1 expression is positively correlated with grades of glioma and inversely correlated with glioma patient's prognosis. Steroid receptor coactivator-1 promotes the proliferation, migration, and tumor growth of GBM cells. Notably, SRC-1 knockdown suppresses the stemness of GBM cells. Mechanistically, long noncoding RNA X-inactive specific transcript (XIST) is regulated by SRC-1 at the posttranscriptional level and mediates the function of SRC-1 in promoting stemness-like properties of GBM. Steroid receptor coactivator-1 can promote the expression of Kruppel-like factor 4 (KLF4) through the XIST/microRNA (miR)-152 axis. Additionally, arenobufagin and bufalin, SRC small molecule inhibitors, can reduce the proliferation and stemness of GBM cells. This study reveals SRC-1 promotes the stemness of GBM by activating the long noncoding RNA XIST/miR-152/KLF4 pathway and provides novel markers for diagnosis and therapy of GBM. CI - (c) 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Gong, Miaomiao AU - Gong M AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Wang, Xun AU - Wang X AD - Department of Neurosurgery, The Third People's Hospital of Dalian, Dalian, China. FAU - Mu, Lin AU - Mu L AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Wang, Yueyue AU - Wang Y AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Pan, Jinjin AU - Pan J AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Yuan, Xiaocheng AU - Yuan X AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Zhou, Haoran AU - Zhou H AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Xing, Jinshan AU - Xing J AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Wang, Rui AU - Wang R AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Sun, Jian AU - Sun J AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Liu, Qiwang AU - Liu Q AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Zhang, Xiya AU - Zhang X AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Wang, Lin AU - Wang L AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Chen, Yiying AU - Chen Y AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Pei, Yandong AU - Pei Y AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Li, Shao AU - Li S AD - College of Basic Medical Sciences, Dalian Medical University, Dalian, China. FAU - Liu, Liang AU - Liu L AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. FAU - Zhao, Yongshun AU - Zhao Y AD - The First Affiliated Hospital, Dalian Medical University, Dalian, China. FAU - Yuan, Yuhui AU - Yuan Y AUID- ORCID: 0000-0002-7109-6703 AD - The Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China. LA - eng GR - 81472492/National Natural Science Foundation of China/ GR - 2019-BS-056/Liaoning Provincial Natural Science Foundation of China/ GR - 201092/Dalian Medical University Talents Innovation and Entrepreneurship Projects/ PT - Journal Article DEP - 20201214 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (KLF4 protein, human) RN - 0 (Klf4 protein, mouse) RN - 0 (Klf4 protein, rat) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (MIRN152 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (XIST non-coding RNA) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) SB - IM EIN - Cancer Sci. 2024 Jan;115(1):324. PMID: 38087965 MH - Animals MH - Brain Neoplasms/genetics/metabolism/*pathology MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic/*physiology MH - Glioblastoma/genetics/metabolism/*pathology MH - Heterografts MH - Humans MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/genetics/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/genetics/metabolism MH - Nuclear Receptor Coactivator 1/*metabolism MH - RNA, Long Noncoding/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Signal Transduction/physiology PMC - PMC7894023 OTO - NOTNLM OT - cancer stem cell OT - glioblastoma OT - lncRNA XIST OT - posttranscriptional regulation OT - steroid receptor coactivator-1 COIS- The authors have no conflict of interest to declare. EDAT- 2020/10/23 06:00 MHDA- 2021/03/02 06:00 PMCR- 2021/02/01 CRDT- 2020/10/22 12:21 PHST- 2020/03/01 00:00 [received] PHST- 2020/09/25 00:00 [revised] PHST- 2020/10/06 00:00 [accepted] PHST- 2020/10/23 06:00 [pubmed] PHST- 2021/03/02 06:00 [medline] PHST- 2020/10/22 12:21 [entrez] PHST- 2021/02/01 00:00 [pmc-release] AID - CAS14685 [pii] AID - 10.1111/cas.14685 [doi] PST - ppublish SO - Cancer Sci. 2021 Feb;112(2):604-618. doi: 10.1111/cas.14685. Epub 2020 Dec 14.