PMID- 33253679 OWN - NLM STAT- MEDLINE DCOM- 20210519 LR - 20231213 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 891 DP - 2021 Jan 15 TI - Lnc NEAT1/miR-29b-3p/Sp1 form a positive feedback loop and modulate bortezomib resistance in human multiple myeloma cells. PG - 173752 LID - S0014-2999(20)30844-X [pii] LID - 10.1016/j.ejphar.2020.173752 [doi] AB - The overall survival of multiple myeloma (MM) patients significantly improved with the use of proteasome inhibitor such as bortezomib. However, resistance to sorafenib limits its use. Bortezomib-resistant MM cells were generated and their bortezomib-resistant properties were confirmed by cell viability and apoptosis assays. To explore functions and underlying mechanisms of long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) on bortezomib resistance in MM, MTT assays, fl ow cytometry analyses, dual luciferase report gene assays, RNA pulldown assays and chromatin immunoprecipitation assays were carried out. NEAT1 and specific protein 1 (Sp1) was upregulated while miR-29b-3p was down regulated in bortezomib-resistant MM cells. NEAT1 promoted Sp1 expression by sponging miR-29b-3p and then enhanced the tolerance of MM cells to bortezomib. Sp1 targeted to NEAT1 promoter region promoting NEAT1 transcription and formed a positive feedback loop. NEAT1 and Sp1 levels were higher and miR-29b-3p was levels were lower in bortezomib-resistant MM patients. NEAT1/miR-29b-3p/Sp1 feedback loop enhanced the tolerance of MM cells to bortezomib. These results indicate potentially valuable targets for overcoming bortezomib resistance for MM. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Che, Feifei AU - Che F AD - Department of Hematology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610072, Sichuan, China. Electronic address: Chefeifei2@126.com. FAU - Ye, Xuemei AU - Ye X AD - Department of Hematology, Dongli Medical District of Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610051, Sichuan, China. FAU - Wang, Yu AU - Wang Y AD - Department of Hematology, Dongli Medical District of Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610051, Sichuan, China. FAU - Ma, Shuyue AU - Ma S AD - Department of Hematology, Dongli Medical District of Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610051, Sichuan, China. FAU - Wang, Xuemei AU - Wang X AD - Department of Hematology, Dongli Medical District of Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, 610051, Sichuan, China. LA - eng PT - Journal Article DEP - 20201128 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Antineoplastic Agents) RN - 0 (MIRN29a microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NEAT1 long non-coding RNA, human) RN - 0 (Proteasome Inhibitors) RN - 0 (RNA, Long Noncoding) RN - 0 (Sp1 Transcription Factor) RN - 0 (SP1 protein, human) RN - 69G8BD63PP (Bortezomib) SB - IM MH - Antineoplastic Agents/*pharmacology MH - Bortezomib/*pharmacology MH - Case-Control Studies MH - Cell Line, Tumor MH - *Drug Resistance, Neoplasm/genetics MH - Feedback, Physiological MH - Gene Expression Regulation, Neoplastic MH - Humans MH - MicroRNAs/genetics/*metabolism MH - Multiple Myeloma/*drug therapy/genetics/metabolism/pathology MH - Proteasome Inhibitors/*pharmacology MH - RNA, Long Noncoding/genetics/*metabolism MH - Sp1 Transcription Factor/genetics/*metabolism OTO - NOTNLM OT - Bortezomib OT - Multiple myeloma OT - NEAT1 OT - Resistance OT - Sp1 OT - miR-29b-3p EDAT- 2020/12/01 06:00 MHDA- 2021/05/20 06:00 CRDT- 2020/11/30 20:10 PHST- 2020/09/16 00:00 [received] PHST- 2020/11/17 00:00 [revised] PHST- 2020/11/19 00:00 [accepted] PHST- 2020/12/01 06:00 [pubmed] PHST- 2021/05/20 06:00 [medline] PHST- 2020/11/30 20:10 [entrez] AID - S0014-2999(20)30844-X [pii] AID - 10.1016/j.ejphar.2020.173752 [doi] PST - ppublish SO - Eur J Pharmacol. 2021 Jan 15;891:173752. doi: 10.1016/j.ejphar.2020.173752. Epub 2020 Nov 28.