Jiang Weidong, Yin Fangying, Bian Xuming, Wang Zhenxiao, Zhang Chaohe
Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, No.4026, Yatai Street, Nanguan District, Changchun 130000, China.
Department of Pediatrics, The Third Norman Bethune Hospital of Jilin University, Xiantai Street, NO.126, Changchun 130033, China.
Int Immunopharmacol. 2025 Feb 20;148:113978. doi: 10.1016/j.intimp.2024.113978. Epub 2025 Jan 28.
To investigate the role of long non-coding RNAs (lncRNAs) in the metabolic reprogramming of gastric cancer through their regulation of mesenchymal stem cells (MSCs) and HERPUD1 protein targets, aiming to elucidate mechanisms that could lead to novel therapeutic strategies.
The RNA-seq was performed on BGC and hMSC-BGC cells to perform LncRNA screening. And we employed cell culture techniques using hMSC-BM and BGC823 cells, treated with various genetic interventions including siRNA and overexpression vectors. Techniques such as cell viability assays, quantitative PCR (qPCR), Western blotting, RNA pull-down and RNA-FISH were utilized to validate the interaction between lncRNA AC012181.2 and HERPUD1 protein. Flow cytometry were utilized to analyze the impacts of lncRNA AC012181.2 on gene and protein expression related to cancer metabolism. Additionally, a tumorigenic model in nude mice was used to observe the in vivo effects.
Modulation of AC012181.2 in MSCs significantly affected the proliferation, migration, and invasion capabilities of BGC823 gastric cancer cells. Knockdown of AC012181.2 resulted in reduced tumor growth in mouse models, along with changes in key gene and protein expression levels associated with cancer metabolism. Overexpression of AC012181.2 showed the opposite effect, enhancing tumor growth and altering cellular behaviors and molecular expressions in favor of cancer progression.
The lncRNA AC012181.2 is crucial for gastric cancer metabolic reprogramming by regulating HERPUD1 Protein. Targeting it offers a promising avenue to impact the tumor microenvironment and develop novel gastric cancer therapies.
通过长链非编码RNA（lncRNA）对间充质干细胞（MSC）和HERPUD1蛋白靶点的调控，研究其在胃癌代谢重编程中的作用，旨在阐明可能导致新治疗策略的机制。
对BGC和hMSC - BGC细胞进行RNA测序以筛选lncRNA。我们采用细胞培养技术，使用hMSC - BM和BGC823细胞，并进行包括siRNA和过表达载体在内的各种基因干预。利用细胞活力测定、定量PCR（qPCR）、蛋白质印迹、RNA下拉和RNA荧光原位杂交等技术验证lncRNA AC012181.2与HERPUD1蛋白之间的相互作用。使用流式细胞术分析lncRNA AC012181.2对癌症代谢相关基因和蛋白表达的影响。此外，利用裸鼠致瘤模型观察体内效应。
MSC中AC012181.2的调节显著影响BGC823胃癌细胞的增殖、迁移和侵袭能力。敲低AC012181.2导致小鼠模型中肿瘤生长减少，同时与癌症代谢相关的关键基因和蛋白表达水平发生变化。AC012181.2的过表达显示出相反的效果，促进肿瘤生长并改变细胞行为和分子表达，有利于癌症进展。
lncRNA AC012181.2通过调节HERPUD1蛋白对胃癌代谢重编程至关重要。靶向它为影响肿瘤微环境和开发新的胃癌治疗方法提供了一条有前景的途径。
