PMID- 31713587 OWN - NLM STAT- MEDLINE DCOM- 20201016 LR - 20231213 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 39 IP - 12 DP - 2019 Dec 20 TI - SP1-DLEU1-miR-4429 feedback loop promotes cell proliferative and anti-apoptotic abilities in human glioblastoma. LID - 10.1042/BSR20190994 [doi] LID - BSR20190994 AB - Mounting studies have revealed that long non-coding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) positively regulated the initiation and development of various human malignant tumors. Nevertheless, the function and mechanism of DLEU1 in human glioblastoma multiforme (GBM) remain elusive and ill-defined. The current study was designed to highlight the functional role and disclose the underlying molecular mechanism by which DLEU1 regulated GBM development. We found that DLEU1 was up-regulated in GBM and DLEU1 knockdown significantly inhibited GBM cell proliferation and induced apoptosis. As predicted by bioinformatics analysis and validated in mechanistic assays, SP1 could bind to the promoter region of DLEU1 to activate DLEU1 transcription. Additionally, miR-4429 was verified as a target gene of DLEU1 and negatively modulated by DLEU1. More importantly, miR-4429 overexpression repressed the mRNA and protein levels of SP1 via binding to the 3'UTR of SP1. Overexpression of SP1 or miR-4429 inhibitor could partly abolish the effect of DLEU1 knockdown on cell viability and apoptosis in GBM. Accordingly, our experimental data revealed that SP1-DLEU1-miR-4429 formed a feedback loop to promote GBM development, providing a new evidence for the role of DLEU1 in GBM. CI - (c) 2019 The Author(s). FAU - Liu, Xiaolei AU - Liu X AD - Department of Neurosurgery, Xianyang Hospital of Yan'an University, Xianyang City, Shaanxi Province 712000, P.R. China. FAU - Chen, Ruwei AU - Chen R AD - Department of Neurosurgery, Binzhou People's Hospital, Shandong Province 256610, P.R. China. FAU - Liu, Lijun AU - Liu L AD - Department of Neurosurgery, Xiangyang No. 1 People's Hospital Affiliated to Hubei University of Medicine, Xiangyang 441000, Hubei, P.R. China. LA - eng PT - Journal Article PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (DLEU1 lncRNA, human) RN - 0 (MIRN4429 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (Sp1 Transcription Factor) RN - 0 (SP1 protein, human) RN - 0 (Tumor Suppressor Proteins) SB - IM MH - Apoptosis/genetics MH - Carcinogenesis/genetics MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - Cell Survival/genetics MH - Gene Expression Regulation, Neoplastic/genetics MH - Glioblastoma/*genetics/pathology MH - Humans MH - MicroRNAs/*genetics MH - RNA, Long Noncoding MH - Sp1 Transcription Factor/*genetics MH - Tumor Suppressor Proteins/*genetics PMC - PMC6900472 OTO - NOTNLM OT - DLEU1 OT - SP1 OT - feedback loop OT - glioblastoma OT - miR-4429 COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2019/11/13 06:00 MHDA- 2020/10/21 06:00 PMCR- 2019/12/06 CRDT- 2019/11/13 06:00 PHST- 2019/04/12 00:00 [received] PHST- 2019/10/29 00:00 [revised] PHST- 2019/11/11 00:00 [accepted] PHST- 2019/11/13 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2019/11/13 06:00 [entrez] PHST- 2019/12/06 00:00 [pmc-release] AID - 221115 [pii] AID - BSR20190994 [pii] AID - 10.1042/BSR20190994 [doi] PST - ppublish SO - Biosci Rep. 2019 Dec 20;39(12):BSR20190994. doi: 10.1042/BSR20190994.