PMID- 36747258 OWN - NLM STAT- MEDLINE DCOM- 20230208 LR - 20230301 IS - 1745-6150 (Electronic) IS - 1745-6150 (Linking) VI - 18 IP - 1 DP - 2023 Feb 6 TI - Upregulation of long intergenic non-coding RNA LINC00326 inhibits non-small cell lung carcinoma progression by blocking Wnt/beta-catenin pathway through modulating the miR-657/dickkopf WNT signaling pathway inhibitor 2 axis. PG - 3 LID - 10.1186/s13062-023-00359-9 [doi] LID - 3 AB - BACKGROUND: Long intergenic non-coding RNA 326 (LINC00326) modulates hepatocarcinogenic lipid metabolism. However, the ability of LINC00326 to modulate the highly aggressive non-small cell lung carcinoma (NSCLC) is unknown. Here, LINC00326 in NSCLC was investigated, together with its effects on tumor malignancy and the underlying mechanisms of action. METHODS: LINC00326 levels in tumor tissues and cell lines were measured by Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and RNA fluorescence in situ hybridization (FISH). Proliferation and apoptosis were assessed in cell lines by Cell Counting Kit-8 (CCK-8), EdU staining assays and flow cytometry, respectively, and tumor growth was measured in mouse models. Possible microRNA targets of LINC00326 were predicted by bioinformatics and verified by RNA pull-down and immunoprecipitation and luciferase reporter assays. Western blotting was used to evaluate the expression of Wnt/beta-catenin-associated proteins. RESULTS: LINC00326 was downregulated in tumor tissues and cell lines. Knockdown of LINC00326 stimulated NSCLC cell proliferation and suppressed apoptosis in vitro, as well as enhancing xenograft tumor growth. LINC00326 sponged miR-657, and dickkopf WNT signaling pathway inhibitor 2 (DKK2) was found to be directly targeted by miR-657, with LINC00326 positively regulating its expression through sponging miR-657. The actions of LINC00326 knockdown on proliferation and apoptosis were reversed by stimulation of the miR-657/DKK2 axis. Furthermore, overexpression of miR-657 mitigated DKK2 inhibition on Wnt/beta-catenin signaling. CONCLUSIONS: LINC00326/miR-657/DKK2 axis signaling blocked tumor-associated functions in NSCLC cells through the targeting Wnt/beta-catenin pathway. This suggests that this pathway could be a target for NSCLC treatment. CI - (c) 2023. The Author(s). FAU - Zhang, Yingqian AU - Zhang Y AD - School of Basic Medical Science, Southwest Medical University, Luzhou, 646000, China. AD - Laboratory of Nonhuman Primate Disease Modeling Research, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. FAU - Yuan, Jiao AU - Yuan J AD - Department of Respirology and Critical Care Medicine, Chengdu Seventh People's Hospital, Chengdu, 610041, Sichuan, China. FAU - Guo, Mengfei AU - Guo M AD - Department of Thoracic Surgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Xiang, Run AU - Xiang R AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China. FAU - Xie, Tianpeng AU - Xie T AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China. FAU - Zhuang, Xiang AU - Zhuang X AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China. FAU - Dai, Wei AU - Dai W AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China. FAU - Li, Qiang AU - Li Q AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China. liqiang1907@vip.sina.com. FAU - Lai, Qi AU - Lai Q AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China. laiqi@swmu.edu.cn. LA - eng GR - 2018-ZRZD-019/Scientific Research Foundation of Southwest Medical University/ GR - 2018-ZRZD-017/Scientific Research Foundation of Southwest Medical University/ GR - 81902890/National Natural Science Foundation of China/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230206 PL - England TA - Biol Direct JT - Biology direct JID - 101258412 RN - 0 (beta Catenin) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (MIRN657 microRNA, human) SB - IM MH - Animals MH - Mice MH - Humans MH - *Carcinoma, Non-Small-Cell Lung/genetics MH - Wnt Signaling Pathway/genetics MH - beta Catenin/genetics MH - Up-Regulation MH - In Situ Hybridization, Fluorescence MH - Cell Line, Tumor MH - *MicroRNAs/genetics/metabolism MH - *Lung Neoplasms/genetics MH - Cell Proliferation/genetics MH - *RNA, Long Noncoding/genetics MH - Cell Movement/genetics MH - Gene Expression Regulation, Neoplastic MH - Apoptosis/genetics PMC - PMC9901116 OTO - NOTNLM OT - DKK2 OT - LINC00326 OT - NSCLC OT - Wnt/beta-catenin pathway OT - miR-657 COIS- The authors declare that they have no competing interests. EDAT- 2023/02/08 06:00 MHDA- 2023/02/09 06:00 PMCR- 2023/02/06 CRDT- 2023/02/07 00:16 PHST- 2022/09/07 00:00 [received] PHST- 2023/01/29 00:00 [accepted] PHST- 2023/02/07 00:16 [entrez] PHST- 2023/02/08 06:00 [pubmed] PHST- 2023/02/09 06:00 [medline] PHST- 2023/02/06 00:00 [pmc-release] AID - 10.1186/s13062-023-00359-9 [pii] AID - 359 [pii] AID - 10.1186/s13062-023-00359-9 [doi] PST - epublish SO - Biol Direct. 2023 Feb 6;18(1):3. doi: 10.1186/s13062-023-00359-9.