Guo Yingying, Zhang Panpan, Gao Zhixing, Liu Xiaotian, Su Chen, Chen Su, An Tao, Hou Jingjing
State Key Laboratory of Stress Cell Biology, School of Life Sciences; Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen 361102, China.
Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361000, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Dec 20. doi: 10.3724/abbs.2024231.
Gastric cancer (GC) is an aggressive tumor type with an intricate pathogenesis and limited therapeutic options. Ubiquitin-specific protease 22 (USP22) is a protein implicated in cell proliferation, metastasis, and tumorigenesis. However, the regulatory mechanisms governing USP22 in GC are still not fully understood. In this study, we perform bioinformatics analysis to identify conserved miRNA recognition sites for miR-200b-5p within the 3'UTR of . Validation via luciferase reporter assay confirms the transcriptional regulation of by miR-200b-5p. Overexpression of miR-200b-5p markedly inhibits the proliferation and migration of GC cells and suppresses tumor growth . Conversely, ectopic expression of USP22 reversed this effect by modulating the NF-κB signaling pathway. Additionally, qPCR analysis reveals an inverse correlation between the miR-200b-5p level and USP22 expression in GC. Collectively, our findings indicate that miR-200b-5p-mediated inhibition of USP22 attenuates cell proliferation by targeting the NF-κB signaling pathway in GC, suggesting that miR-200b-5p and USP22 could serve as potential diagnostic or therapeutic targets for gastric cancer and other related human diseases.
胃癌(GC)是一种侵袭性肿瘤类型,其发病机制复杂,治疗选择有限。泛素特异性蛋白酶22(USP22)是一种与细胞增殖、转移和肿瘤发生有关的蛋白质。然而,USP22在胃癌中的调控机制仍未完全明确。在本研究中,我们进行了生物信息学分析,以鉴定[此处原文缺失相关基因名称] 3'UTR内miR-200b-5p的保守miRNA识别位点。通过荧光素酶报告基因检测进行验证,证实了miR-200b-5p对[此处原文缺失相关基因名称]的转录调控。miR-200b-5p的过表达显著抑制了胃癌细胞的增殖和迁移,并抑制了肿瘤生长。相反,USP22的异位表达通过调节NF-κB信号通路逆转了这种作用。此外,qPCR分析显示胃癌中miR-200b-5p水平与USP22表达呈负相关。总体而言,我们的研究结果表明,miR-200b-5p介导的对USP22的抑制通过靶向胃癌中的NF-κB信号通路减弱了细胞增殖,这表明miR-200b-5p和USP22可能作为胃癌及其他相关人类疾病的潜在诊断或治疗靶点。