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高表达的 B3GALT5-AS1 通过募集 WDR5 介导 B3GALT5 并调控 β-catenin/ZEB1 轴促进胃癌进展。

Highly expressed B3GALT5-AS1 contributes to gastric cancer progression by recruiting WDR5 to mediate B3GALT5 and regulating β-catenin/ZEB1 axis.

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.

Medical School of Nantong University, Nantong University, Nantong, Jiangsu, China.

出版信息

J Cell Mol Med. 2024 Sep;28(17):e70061. doi: 10.1111/jcmm.70061.

DOI:10.1111/jcmm.70061
PMID:39224045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11369489/
Abstract

Long non-coding RNAs (lncRNAs) play an important role in the progression of gastric cancer (GC), but its specific regulatory mechanism remains to be further studied. We previously identified that lncRNA B3GALT5-AS1 was upregulated in GC serum. Here, we investigated the functions and molecular mechanisms of B3GALT5-AS1 in GC tumorigenesis. qRT-PCR was used to detect B3GALT5-AS1 expression in GC. EdU, CCK-8, and colony assays were utilized to assess the proliferation ability of B3GAL5-AS1, and transwell, tube formation assay were used to assess the invasion and metastasis ability. Mechanically, FISH and nuclear plasmolysis PCR identified the subcellular localization of B3GALT5-AS1. RIP and CHIP assays were used to analyse the regulation of B3GALT5-AS1 and B3GALT5. We observed that B3GALT5-AS1 was highly expressed in GC, and silencing B3GALT5-AS1 could inhibit the proliferation, invasion, and migratory capacities of GC. Additionally, B3GALT5-AS1 was bound to WDR5 and modulated the expression of B3GALT5 via regulating the ZEB1/β-catenin pathway. High-expressed B3AGLT5-AS1 promoted GC tumorigenesis and regulated B3GALT5 expression via recruiting WDR5. Our study is expected to provide a new idea for clinical diagnosis and treatment.

摘要

长链非编码 RNA(lncRNAs)在胃癌(GC)的进展中发挥着重要作用,但具体的调控机制仍有待进一步研究。我们之前发现 lncRNA B3GALT5-AS1 在 GC 血清中上调。在这里,我们研究了 B3GALT5-AS1 在 GC 肿瘤发生中的功能和分子机制。qRT-PCR 用于检测 GC 中 B3GALT5-AS1 的表达。EdU、CCK-8 和集落测定用于评估 B3GAL5-AS1 的增殖能力,Transwell 和管形成测定用于评估侵袭和转移能力。从机制上讲,FISH 和核质分离 PCR 确定了 B3GALT5-AS1 的亚细胞定位。RIP 和 CHIP 测定用于分析 B3GALT5-AS1 和 B3GALT5 的调节。我们观察到 B3GALT5-AS1 在 GC 中高度表达,沉默 B3GALT5-AS1 可以抑制 GC 的增殖、侵袭和迁移能力。此外,B3GALT5-AS1 与 WDR5 结合,并通过调节 ZEB1/β-catenin 通路调节 B3GALT5 的表达。高表达的 B3AGLT5-AS1 通过招募 WDR5 促进 GC 肿瘤发生并调节 B3GALT5 的表达。我们的研究有望为临床诊断和治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/5904dcefe805/JCMM-28-e70061-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/0066e85d5536/JCMM-28-e70061-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/798011884028/JCMM-28-e70061-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/df56b3860195/JCMM-28-e70061-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/1ed62e4a6d59/JCMM-28-e70061-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/6f243ce8883a/JCMM-28-e70061-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/0bdc1e7a1cee/JCMM-28-e70061-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/91cc474916d1/JCMM-28-e70061-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/e923f3796acc/JCMM-28-e70061-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/5904dcefe805/JCMM-28-e70061-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/0066e85d5536/JCMM-28-e70061-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/798011884028/JCMM-28-e70061-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/df56b3860195/JCMM-28-e70061-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/1ed62e4a6d59/JCMM-28-e70061-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/6f243ce8883a/JCMM-28-e70061-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/0bdc1e7a1cee/JCMM-28-e70061-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/91cc474916d1/JCMM-28-e70061-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/e923f3796acc/JCMM-28-e70061-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fe0/11369489/5904dcefe805/JCMM-28-e70061-g003.jpg

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