PMID- 37573302 OWN - NLM STAT- MEDLINE DCOM- 20230814 LR - 20231121 IS - 1471-230X (Electronic) IS - 1471-230X (Linking) VI - 23 IP - 1 DP - 2023 Aug 12 TI - A novel long non-coding RNA XLOC_004787, is associated with migration and promotes cancer cell proliferation by downregulating mir-203a-3p in gastric cancer. PG - 280 LID - 10.1186/s12876-023-02912-2 [doi] LID - 280 AB - BACKGROUND: Long noncoding RNAs (lncRNAs) have been identified as important regulatory factors implicated in a wide array of diseases, including various forms of cancer. However, the roles of most lncRNAs in the progression of gastric cancer (GC) remain largely unexplored. This study investigates the biological function and underlying mechanism of a novel lncRNA, XLOC_004787 in GC. METHODS: The location of XLOC_004787 in GES-1 cells and HGC-27 cells were detected by fluorescence in situ hybridization (FISH) assay. The expression levels of XLOC_004787 were assessed using quantitative real-time fluorescence PCR (qRT-PCR) in various cell lines, including GES-1, MGC-803, MKN-45, BGC-823, SGC-7901, and HGC-27 cells. Functional assays such as Transwell migration, cell counting kit-8 (CCK-8), and colony formation experiments were employed to analyze the effects of XLOC_004787 and miR-203a-3p on cell migration and proliferation. Protein levels associated with GC in these cell lines were examined by Western blotting. The intracellular localization of beta-catenin and P-Smad2/3 was assessed using immunofluorescence (IF) assay. Additionally, the interaction between XLOC_004787 and miR-203a-3p was investigated using a dual luciferase assay. RESULTS: XLOC_004787 was localized at both the cytoplasm and nucleus of GES-1 cells and HGC-27 cells. Compared to normal tissues and GES-1 cells, XLOC_004787 expression was significantly upregulated in GC tissues and cells, with the highest and lowest expression observed in SGC-7901 and HGC-27 cells, respectively. Furthermore, a reduced expression of XLOC_004787 was seen to inhibit migration and proliferation in SGC-7901 cells. Western blotting analysis revealed that a decrease in XLOC_004787 expression correspondingly decreased the expression of N-cadherin, mmp2, mmp9, Snail, Vimentin, beta-catenin, C-myc, Cyclin D1, and TGF-beta, while concurrently increasing E-cadherin expression. This was also associated with diminished expression of P-Smad2/3 in relation to Smad2/3, and reduced P-Gsk3beta expression in comparison to Gsk3beta. Additionally, the nuclear entry of P-Smad2/3 and beta-catenin was reduced by lower XLOC_004787 expression. Amplifying XLOC_004787 expression via pcDNA_XLOC_004787 suggested a potential for cancer promotion. Notably, XLOC_004787 was found to negatively regulate mir-203a-3p expression, with potential binding sites identified between the two. Higher mir-203a-3p expression was observed to decrease migration and proliferation, and enhance E-cadherin expression. Conversely, suppression of mir-203a-3p expression suggested a potential promotion of proliferation and migration in GC cells. CONCLUSIONS: These results suggest that XLOC_004787, found to be upregulated in GC tissues, potentially promotes proliferation and migration in GC cells. This occurs through the activation of TGF-beta and Wnt/beta-catenin signaling pathways and the expression of EMT-related proteins. Additionally, XLOC_004787 may influence cell migration and proliferation by modulating the signaling pathway via the adsorption and inhibition of mir-203a-3p. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Miao, Renjie AU - Miao R AD - Department of Clinical Laboratory, Affiliated Third Hospital of Zhenjiang to Jiangsu University, Zhenjiang, 212001, Jiangsu, China. FAU - Yao, Zhendong AU - Yao Z AD - Department of Gastroenterology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, Jiangsu, China. FAU - Hu, Bingheng AU - Hu B AD - The Affiliated Hospital of Jiangsu University, Yizheng Road, Zhenjiang, 212013, Jiangsu, China. FAU - Jin, Tao AU - Jin T AD - Department of Gastroenterology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, 214200, Jiangsu, China. FAU - Zhu, Donglai AU - Zhu D AD - Department of Clinical Laboratory, Affiliated Third Hospital of Zhenjiang to Jiangsu University, Zhenjiang, 212001, Jiangsu, China. FAU - Shi, Yun AU - Shi Y AD - Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu, China. FAU - Gong, Yuhua AU - Gong Y AD - Department of Clinical Laboratory, Affiliated Third Hospital of Zhenjiang to Jiangsu University, Zhenjiang, 212001, Jiangsu, China. FAU - Shao, Shihe AU - Shao S AD - Department of Clinical Laboratory, Affiliated Third Hospital of Zhenjiang to Jiangsu University, Zhenjiang, 212001, Jiangsu, China. FAU - Shao, Chen AU - Shao C AUID- ORCID: 0000-0002-0676-1295 AD - The Affiliated Hospital of Jiangsu University, Yizheng Road, Zhenjiang, 212013, Jiangsu, China. shaochen84@163.com. LA - eng PT - Journal Article DEP - 20230812 PL - England TA - BMC Gastroenterol JT - BMC gastroenterology JID - 100968547 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (beta Catenin) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - 0 (Cadherins) SB - IM MH - Humans MH - *MicroRNAs/genetics/metabolism MH - *RNA, Long Noncoding/genetics MH - *Stomach Neoplasms/genetics/metabolism MH - beta Catenin/genetics/metabolism MH - Glycogen Synthase Kinase 3 beta/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Wnt Signaling Pathway/genetics MH - Cadherins/genetics MH - Cell Movement/genetics MH - Gene Expression Regulation, Neoplastic PMC - PMC10422700 OTO - NOTNLM OT - Gastric cancer OT - Migration OT - Mir-203a-3p OT - Proliferation OT - XLOC_004787 COIS- There is no conflict of interest in the publication of this article. EDAT- 2023/08/13 00:43 MHDA- 2023/08/14 06:42 PMCR- 2023/08/12 CRDT- 2023/08/12 23:13 PHST- 2022/09/14 00:00 [received] PHST- 2023/08/02 00:00 [accepted] PHST- 2023/08/14 06:42 [medline] PHST- 2023/08/13 00:43 [pubmed] PHST- 2023/08/12 23:13 [entrez] PHST- 2023/08/12 00:00 [pmc-release] AID - 10.1186/s12876-023-02912-2 [pii] AID - 2912 [pii] AID - 10.1186/s12876-023-02912-2 [doi] PST - epublish SO - BMC Gastroenterol. 2023 Aug 12;23(1):280. doi: 10.1186/s12876-023-02912-2.