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长链非编码RNA CHAF1B-2通过激活Wnt/β-连环蛋白信号通路促进胃癌的发生。

lncRNA CHAF1B-2 contributes to the tumorigenesis of gastric cancer by activating the Wnt/β-catenin pathway.

作者信息

Tian Shao-Qi, Shen Jun-Jie, Sun Dao-Ping, Chen Wen-Ming

机构信息

Department of Oncology, Jining Hospital of Xiyuan Hospital of CACMS, Jining, 272011, Shandong Province, China.

Department of Oncology, Tianchang Traditional Chinese Medicine Hospital, Tianchang, 239300, Anhui Province, China.

出版信息

Sci Rep. 2025 Jan 2;15(1):568. doi: 10.1038/s41598-024-84344-w.

DOI:10.1038/s41598-024-84344-w
PMID:39747989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11695584/
Abstract

Lnc-CHAF1B-2, a newly discovered long noncoding RNA (lncRNA), plays a significant role in the evolution and prognosis of diverse neoplasms. However, its role in the development of gastric cancer is not yet fully understood. Using bioinformatics analysis of gastric cancer RNA-seq data from The Cancer Genome Atlas (TCGA) database, we investigated the expression of lnc-CHAF1B-2 in gastric carcinoma and its associated molecular signalling pathways. Verification through an array of in vivo and in vitro experiments-namely, EdU incorporation, flow cytometry, trans-well migration and invasion assays, subcutaneous tumour formation in nude mice, and western blot analysis-was conducted. We revealed notable upregulation of lnc-CHAF1B-2 in gastric cancer tissues. Furthermore, a positive correlation was detected between lnc-CHAF1B-2 levels and the occurrence of distant metastases in patients, which was inversely related to their prognostic outlook and survival rates. Moreover, our findings confirmed that lnc-CHAF1B-2 enhanced the proliferation, invasion, and migration of gastric cancer cells while inhibiting apoptosis both in vitro and in vivo. Mechanistically, lnc-CHAF1B-2 promoted the progression of gastric cancer through activating the Wnt/β-catenin signalling pathway. Thus, lnc-CHAF1B-2 and its regulation of the Wnt/β-catenin signalling pathway have emerged as prospective therapeutic targets in gastric cancer management.

摘要

Lnc-CHAF1B-2是一种新发现的长链非编码RNA(lncRNA),在多种肿瘤的发生发展及预后中发挥重要作用。然而,其在胃癌发生发展中的作用尚未完全明确。我们利用癌症基因组图谱(TCGA)数据库中胃癌RNA测序数据进行生物信息学分析,研究了lnc-CHAF1B-2在胃癌中的表达及其相关分子信号通路。通过一系列体内外实验进行验证,即EdU掺入实验、流式细胞术、Transwell迁移和侵袭实验、裸鼠皮下肿瘤形成实验以及蛋白质免疫印迹分析。我们发现胃癌组织中lnc-CHAF1B-2显著上调。此外,检测到患者体内lnc-CHAF1B-2水平与远处转移的发生呈正相关,这与患者的预后和生存率呈负相关。而且,我们的研究结果证实,lnc-CHAF1B-2在体外和体内均能增强胃癌细胞的增殖、侵袭和迁移能力,同时抑制细胞凋亡。机制上,lnc-CHAF1B-2通过激活Wnt/β-连环蛋白信号通路促进胃癌进展。因此,lnc-CHAF1B-2及其对Wnt/β-连环蛋白信号通路的调控已成为胃癌治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/756d940be6bf/41598_2024_84344_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/fd9335c13f9e/41598_2024_84344_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/89cc3da611fb/41598_2024_84344_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/b20c2990bb64/41598_2024_84344_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/938912f8a6d7/41598_2024_84344_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/473c976180fe/41598_2024_84344_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/756d940be6bf/41598_2024_84344_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/fd9335c13f9e/41598_2024_84344_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/89cc3da611fb/41598_2024_84344_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/b20c2990bb64/41598_2024_84344_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/938912f8a6d7/41598_2024_84344_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/473c976180fe/41598_2024_84344_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8d/11695584/756d940be6bf/41598_2024_84344_Fig6_HTML.jpg

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