PMID- 31680444 OWN - NLM STAT- MEDLINE DCOM- 20210317 LR - 20210317 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 24 IP - 1 DP - 2020 Jan TI - LncRNA HOXA11-AS regulates calcium oxalate crystal-induced renal inflammation via miR-124-3p/MCP-1. PG - 238-249 LID - 10.1111/jcmm.14706 [doi] AB - Long noncoding RNA (lncRNA) has been suggested to play an important role in a variety of diseases over the past decade. In a previous study, we identified a novel lncRNA, termed HOXA11-AS, which was significantly up-regulated in calcium oxalate (CaOx) nephrolithiasis. However, the biological function of HOXA11-AS in CaOx nephrolithiasis remains poorly defined. Here, we demonstrated that HOXA11-AS was significantly up-regulated in CaOx nephrolithiasis both in vivo and in vitro. Gain-/loss-of-function studies revealed that HOXA11-AS inhibited proliferation, promoted apoptosis and aggravated cellular damage in HK-2 cells exposed to calcium oxalate monohydrate (COM). Further investigations showed that HOXA11-AS regulated monocyte chemotactic protein 1 (MCP-1) expression in HK-2 cell model of CaOx nephrolithiasis. In addition, online bioinformatics analysis and dual-luciferase reporter assay results showed that miR-124-3p directly bound to HOXA11-AS and the 3'UTR of MCP-1. Furthermore, rescue experiment results revealed that HOXA11-AS functioned as a competing endogenous RNA to regulate MCP-1 expression through sponging miR-124-3p and that overexpression of miR-124-3p restored the inhibitory effect of proliferation, promotion effects of apoptosis and cell damage induced by HOXA11-AS overexpression. Taken together, HOXA11-AS mediated CaOx crystal-induced renal inflammation via the miR-124-3p/MCP-1 axis, and this outcome may provide a good potential therapeutic target for nephrolithiasis. CI - (c) 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. FAU - Li, Yinhui AU - Li Y AUID- ORCID: 0000-0001-7900-6103 AD - Department of Nephrology, Changhai Hospital, The Naval Military Medical University, Shanghai, China. FAU - Yan, Guiling AU - Yan G AD - Department of Breast and Thyroid Surgery, Changhai Hospital, The Naval Military Medical University, Shanghai, China. AD - Department of General Surgery, The Naval Hospital, Eastern Theater PLA, Zhoushan, Zhejiang, China. FAU - Zhang, Jie AU - Zhang J AD - Department of Nephrology, Changhai Hospital, The Naval Military Medical University, Shanghai, China. FAU - Chen, Wei AU - Chen W AD - Department of Nephrology, Changhai Hospital, The Naval Military Medical University, Shanghai, China. FAU - Ding, Tao AU - Ding T AD - Department of Nephrology, Changhai Hospital, The Naval Military Medical University, Shanghai, China. FAU - Yin, Yupeng AU - Yin Y AD - Department of Medical Genetics, The Naval Military Medical University, Shanghai, China. FAU - Li, Minghan AU - Li M AD - Department of Medical Genetics, The Naval Military Medical University, Shanghai, China. FAU - Zhu, Yiqing AU - Zhu Y AD - Department of Medical Genetics, The Naval Military Medical University, Shanghai, China. FAU - Sun, Shuhan AU - Sun S AD - Department of Medical Genetics, The Naval Military Medical University, Shanghai, China. FAU - Yuan, Ji Hang AU - Yuan JH AD - Department of Medical Genetics, The Naval Military Medical University, Shanghai, China. FAU - Guo, Zhiyong AU - Guo Z AUID- ORCID: 0000-0001-7816-3270 AD - Department of Nephrology, Changhai Hospital, The Naval Military Medical University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191103 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (3' Untranslated Regions) RN - 0 (Chemokine CCL2) RN - 0 (MIRN124 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 2612HC57YE (Calcium Oxalate) RN - Nephrolithiasis, Calcium Oxalate SB - IM MH - 3' Untranslated Regions/genetics MH - Animals MH - Apoptosis/drug effects/genetics MH - Base Sequence MH - Calcium Oxalate/*toxicity MH - Cell Line MH - Cell Proliferation/drug effects/genetics MH - Chemokine CCL2/*metabolism MH - Crystallization MH - Gene Knockdown Techniques MH - Humans MH - Inflammation/*genetics/pathology MH - Kidney/metabolism/*pathology MH - Male MH - Mice, Inbred C57BL MH - MicroRNAs/*metabolism MH - Nephrolithiasis/genetics MH - RNA, Long Noncoding/genetics/*metabolism MH - Up-Regulation/drug effects/genetics PMC - PMC6933336 OTO - NOTNLM OT - HOXA11-AS OT - MCP-1 OT - calcium oxalate OT - lncRNA OT - mir-124-3p COIS- The authors confirm that there are no conflicts of interest. EDAT- 2019/11/05 06:00 MHDA- 2021/03/18 06:00 PMCR- 2020/01/01 CRDT- 2019/11/05 06:00 PHST- 2019/01/15 00:00 [received] PHST- 2019/08/25 00:00 [revised] PHST- 2019/09/01 00:00 [accepted] PHST- 2019/11/05 06:00 [pubmed] PHST- 2021/03/18 06:00 [medline] PHST- 2019/11/05 06:00 [entrez] PHST- 2020/01/01 00:00 [pmc-release] AID - JCMM14706 [pii] AID - 10.1111/jcmm.14706 [doi] PST - ppublish SO - J Cell Mol Med. 2020 Jan;24(1):238-249. doi: 10.1111/jcmm.14706. Epub 2019 Nov 3.