Academic Journal
[MIS18BP1 regulates epithelial-mesenchymal transition, proliferation, and migration of renal cancer cells via the PI3K/AKT pathway].
| Τίτλος: | [MIS18BP1 regulates epithelial-mesenchymal transition, proliferation, and migration of renal cancer cells via the PI3K/AKT pathway]. |
|---|---|
| Συγγραφείς: | Zhao B; Department of Pathogenic Biology, School of Basic Medical Sciences, Qingdao University, Qingdao 266071, China.; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266011, China., Tan X; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266011, China., Liang X; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266011, China.; College of Medical Laboratory Science, Shandong Second Medical University, Weifang 261053, China., Pan Y; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266011, China.; College of Medical Laboratory Science, Shandong Second Medical University, Weifang 261053, China., Yuan J; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266011, China., Song W; Department of Clinical Laboratory, Qingdao Municipal Hospital, Qingdao 266011, China. |
| Πηγή: | Nan fang yi ke da xue xue bao = Journal of Southern Medical University [Nan Fang Yi Ke Da Xue Xue Bao] 2026 Sept 20; Vol. 46 (9), pp. 2159-2172. |
| Τύπος έκδοσης: | English Abstract; Journal Article |
| Γλώσσα: | Chinese |
| Στοιχεία περιοδικού: | Publisher: Nanfang yi ke da xue xue bao bian ji bu Country of Publication: China NLM ID: 101266132 Publication Model: Print Cited Medium: Print ISSN: 1673-4254 (Print) Linking ISSN: 16734254 NLM ISO Abbreviation: Nan Fang Yi Ke Da Xue Xue Bao Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Guangzhou : Nanfang yi ke da xue xue bao bian ji bu, 2005- |
| Ιατρικοί όροι (MeSH): | Kidney Neoplasms*/metabolism , Kidney Neoplasms*/pathology , Carcinoma, Renal Cell*/metabolism , Carcinoma, Renal Cell*/pathology , Epithelial-Mesenchymal Transition*, Proto-Oncogene Proteins c-akt/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Humans ; Cell Proliferation ; Cell Movement ; Cell Line, Tumor ; Signal Transduction ; Gene Expression Regulation, Neoplastic ; Female |
| Περίληψη: | Objectives: To explore the regulatory role of MIS18BP1 in epithelial-mesenchymal transition (EMT), proliferation, and migration of renal cancer cells and its molecular mechanism. Methods: TCGA and GEO databases were used to analyze the expression patterns of MIS18BP1 in kidney renal clear cell carcinoma (KIRC), and its differential expression between tumor and adjacent tissues was validated by immunohistochemistry. The diagnostic value of MIS18BP1 and its correlation with clinicopathological parameters and immune infiltration were evaluated. Weighted gene co-expression network analysis (WGCNA) was performed to identify MIS18BP1-related gene modules for functional enrichment analysis. In renal cancer cell lines (786-O and ACHN), the effects of lentivirus-mediated MIS18BP1 knockdown on cell proliferation and migration were evaluated using CCK-8, colony formation, Transwell, and wound healing assays. Western blotting was performed to determine the expression levels of EMT-related proteins and PI3K/AKT pathway-related proteins, and rescue experiments were carried out using 740Y-P (a PI3K activator). Results: MIS18BP1 was significantly overexpressed in KIRC tissues and in 786-O and ACHN cells compared with normal renal epithelial cells (HK-2). MIS18BP1 expression level was positively correlated with TNM stage and pathological grade, and showed good diagnostic performance for KIRC (AUC=0.693-0.885). WGCNA and enrichment analyses indicated that MIS18BP1-related genes were significantly enriched in the PI3K/AKT signaling pathway. In cultured renal cancer cells, MIS18BP1 knockdown significantly inhibited the proliferation, migration, and colony-forming ability of the cells, resulting also in decreased expression of N-cadherin and vimentin, increased expression of E-cadherin, and significantly lowered phosphorylation levels of PI3K and AKT. Treatment with 740Y-P partially reversed the inhibitory effects of MIS18BP1 knockdown on cell proliferation and migration. Conclusions: MIS18BP1 is overexpressed in renal cancer and is associated with unfavorable clinical features. High expression of MIS18BP1 enhances proliferation and migration of renal cancer cells possibly by promoting EMT via activating the PI3K/AKT signaling pathway. |
| References: | CA Cancer J Clin. 2024 May-Jun;74(3):229-263. (PMID: 38572751) Cancer Res. 2017 Nov 1;77(21):e108-e110. (PMID: 29092952) Nat Rev Mol Cell Biol. 2016 Jan;17(1):16-29. (PMID: 26601620) Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96. (PMID: 24556840) Br J Pharmacol. 2021 Jun;178(11):2351-2369. (PMID: 33645631) Cold Spring Harb Perspect Biol. 2012 Sep 01;4(9):a011189. (PMID: 22952397) Nat Cell Biol. 2004 Oct;6(10):931-40. (PMID: 15448698) J Cell Biol. 2011 Sep 19;194(6):855-71. (PMID: 21911481) J Clin Oncol. 2020 Dec 20;38(36):4240-4248. (PMID: 33108238) Cancer Cell Int. 2025 Aug 25;25(1):314. (PMID: 40851082) EMBO Rep. 2024 Aug;25(8):3348-3372. (PMID: 38951710) Oncogene. 2005 Nov 14;24(50):7443-54. (PMID: 16288291) Cell Mol Life Sci. 2013 Feb;70(3):387-406. (PMID: 22729156) Mol Genet Genomics. 2026 Mar 04;301(1):. (PMID: 41779200) Dev Cell. 2016 Jun 6;37(5):413-27. (PMID: 27270040) Biology (Basel). 2017 Jan 24;6(1):. (PMID: 28125021) Open Biol. 2020 Jun;10(6):200051. (PMID: 32516549) J Biol Chem. 2012 Mar 9;287(11):8598-612. (PMID: 22270359) Cell Rep. 2016 Jun 7;15(10):2127-2135. (PMID: 27239045) Nat Commun. 2021 Jun 8;12(1):3444. (PMID: 34103528) F1000Res. 2016 Jul 19;5:1745. (PMID: 27853512) Nat Rev Dis Primers. 2017 Mar 09;3:17009. (PMID: 28276433) Biomedicines. 2025 Jan 26;13(2):. (PMID: 40002717) Lancet. 2023 Jul 15;402(10397):185-195. (PMID: 37290461) N Engl J Med. 2019 Mar 21;380(12):1116-1127. (PMID: 30779529) Med Oncol. 2025 Apr 9;42(5):156. (PMID: 40205244) CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. (PMID: 38230766) J Cell Biol. 2007 Jul 30;178(3):437-51. (PMID: 17646396) Curr Treat Options Oncol. 2023 Dec;24(12):1889-1916. (PMID: 38153686) Cell. 2009 Nov 25;139(5):871-90. (PMID: 19945376) Dev Cell. 2007 Jan;12(1):17-30. (PMID: 17199038) Eur Urol. 2022 Nov;82(5):458-468. (PMID: 35853783) Oncogene. 2012 Sep 6;31(36):4022-33. (PMID: 22158034) Cancer Cell Int. 2024 Jul 27;24(1):265. (PMID: 39068456) |
| Grant Information: | 31971191 National Natural Science Foundation of China |
| Contributed Indexing: | Keywords: MIS18BP1; PI3K/AKT signaling pathway; cell migration; cell proliferation; clear cell renal cell carcinoma; epithelial-mesenchymal transition Local Abstract: [Publisher, Chinese] 目的: 探讨MIS18BP1通过PI3K/AKT信号通路调控肾癌细胞上皮-间充质转化（EMT）、增殖和迁移的作用及分子机制。方法: 基于TCGA和GEO数据库分析MIS18BP1在肾透明细胞癌（KIRC）中的表达特征，并通过免疫组化验证在肾癌及癌旁组织中的表达差异，进一步探讨其诊断价值及与临床病理参数、免疫浸润的相关性（P<0.05）;采用加权基因共表达网络分析（WGCNA）筛选MIS18BP1相关基因模块并进行功能富集分析;通过慢病毒转染技术敲低肾癌细胞系786-O和ACHN中MIS18BP1的表达，采用CCK-8、克隆形成、Transwell与划痕愈合实验检测细胞增殖与迁移能力;Western blotting检测EMT标志蛋白（E-cadherin、N-cadherin、Vimentin）及PI3K/AKT通路关键蛋白（PI3K、p-AKT、AKT）的表达变化，进一步采用740Y-P（PI3K激活剂）处理进行回复实验。结果: MIS18BP1在KIRC组织中高表达，与正常肾上皮细胞HK-2相比，MIS18BP1在786-O和ACHN中均升高，其表达水平与肿瘤TNM分期、病理分级呈正相关，且对KIRC具有良好的诊断效能（AUC=0.693~0.885）;WGCNA与富集分析显示MIS18BP1相关基因富集于PI3K/AKT信号通路;细胞实验证实，敲低MIS18BP1可抑制肾癌细胞的增殖、迁移与克隆形成能力（P<0.05），同时下调N-cadherin、Vimentin表达，上调E-cadherin表达，并降低PI3K与AKT的磷酸化水平（P<0.05）。740Y-P处理可部分逆转敲低MIS18BP1所致的增殖和迁移抑制效应。结论: MIS18BP1在肾癌中高表达且与不良临床特征相关，其可能通过激活PI3K/AKT信号通路促进EMT进程，从而增强肾癌细胞的增殖与迁移能力。. |
| Substance Nomenclature: | EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) |
| Entry Date(s): | Date Created: 20260930 Date Completed: 20260930 Latest Revision: 20261001 |
| Update Code: | 20261001 |
| DOI: | 10.12122/j.issn.1673-4254.2026.09.15 |
| PMID: | 42812061 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1673-4254 |
|---|---|
| DOI: | 10.12122/j.issn.1673-4254.2026.09.15 |