PMID- 34195070 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220424 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - Long Noncoding RNA SNHG12 Promotes Gastric Cancer Proliferation by Binding to HuR and Stabilizing YWHAZ Expression Through the AKT/GSK-3beta Pathway. PG - 645832 LID - 10.3389/fonc.2021.645832 [doi] LID - 645832 AB - BACKGROUND: Gastric cancer (GC) is a malignancy with high morbidity and mortality rates worldwide. SNHG12 is a long noncoding RNA (lncRNA) commonly involved many types of cancers in the contexts of tumorigenesis, migration and drug resistance. Nevertheless, its role in GC proliferation is poorly understood. METHODS: Bioinformatics and qRT-PCR assays were used to analyze the expression of SNHG12 in GC tissues and cells. In vitro and in vivo experiments were conducted to detect the role of SNHG12 in GC development. qRT-PCR, PCR, western blotting (WB), RNA binding protein immunoprecipitation (RIP), immunoprecipitation (IP), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and in situ hybridization (ISH) were performed to investigate the underlying mechanisms by which SNHG12 promotes GC proliferation. RESULTS: SNHG12 was highly expressed in GC cells and tissues, and predicted poor survival. In vitro and in vivo assays showed that SNHG12 knockdown inhibited GC proliferation, while SNHG12 overexpression promoted GC proliferation. Further experiments confirmed that SNHG12 was mainly located in the cytoplasm and bound to HuR. Bioinformatics analysis predicted that YWHAZ was the common target of SNHG12 and HuR, and that the "SNHG12-HuR" complex enhanced the stability of YWHAZ mRNA. Furthermore, YWHAZ, which was highly expressed in GC, predicted poor survival and promoted GC proliferation by phosphorylating AKT. Rescue assays verified that SNHG12 promoted GC proliferation by activating the AKT/GSK-3beta pathway. CONCLUSIONS: SNHG12 binds to HuR and stabilizes YWHAZ. SNHG12 promotes GC proliferation via modulation of the YWHAZ/AKT/GSK-3beta axis in vitro and in vivo. Thus, SNHG12 could become a novel therapeutic target for anti-tumor therapy. CI - Copyright (c) 2021 Zhang, Beeharry, Zheng, Wang, Li, Zhu and Li. FAU - Zhang, Tianqi AU - Zhang T AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Beeharry, Maneesh Kumarsing AU - Beeharry MK AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zheng, Yanan AU - Zheng Y AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Zhenqiang AU - Wang Z AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Jianfang AU - Li J AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhu, Zhenggang AU - Zhu Z AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Chen AU - Li C AD - Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20210614 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8236831 OTO - NOTNLM OT - HuR OT - SNHG12 OT - YWHAZ OT - gastric cancer OT - proliferation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/07/02 06:00 MHDA- 2021/07/02 06:01 PMCR- 2021/01/01 CRDT- 2021/07/01 07:02 PHST- 2020/12/24 00:00 [received] PHST- 2021/05/17 00:00 [accepted] PHST- 2021/07/01 07:02 [entrez] PHST- 2021/07/02 06:00 [pubmed] PHST- 2021/07/02 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.645832 [doi] PST - epublish SO - Front Oncol. 2021 Jun 14;11:645832. doi: 10.3389/fonc.2021.645832. eCollection 2021.