1. The mechanism study of LncRNA AC012181.2 targeting HERPUD1 protein in regulating stromal stem cells participating in metabolic reprogramming for gastric cancer metastasis.
- Author
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Jiang W, Yin F, Bian X, Wang Z, and Zhang C
- Subjects
- Animals, Humans, Cell Line, Tumor, Mice, Gene Expression Regulation, Neoplastic, Cell Movement, Mice, Inbred BALB C, Membrane Proteins genetics, Membrane Proteins metabolism, Neoplasm Metastasis, Metabolic Reprogramming, Stomach Neoplasms pathology, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Mesenchymal Stem Cells metabolism, Mice, Nude, Cell Proliferation
- Abstract
Objective: 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., Method: 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., Result: 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., Conclusion: 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)
- Published
- 2025
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