The present study aims to investigate the roles of nuclear-enriched abundant transcript 1 (NEAT1) in the regulation of oxaliplatin resistance to gastric cancer (GC). Oxaliplatin-resistant cell lines were constructed using stepwise selection. NEAT1 knockdown and overexpression of NEAT1 were performed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and colony formation assays were used to evaluate cell proliferation. Propidium iodide (PI) and annexin V staining were used to evaluate cell apoptosis. A dual-luciferase reporter assay was used to evaluate the molecular interactions. Quantitative polymerase chain reaction (qPCR) was used to determine messenger RNA (mRNA) expression. Western blotting was used to determine the protein expression. Kaplan-Meier's analysis was performed to evaluate the relationship between NEAT1 and poor prognosis in GC. NEAT1 was upregulated in oxaliplatin-resistant GC cells and associated with poor prognosis in GC patients. NEAT1 knockdown suppressed oxaliplatin resistance, whereas overexpression of NEAT1 induced oxaliplatin resistance. In addition, the expressions of NEAT1 were negatively associated with miR-26 expressions. Overexpression of NEAT1 attenuated the inhibitory effects of miR-26 on the enhancer of zeste homolog 2 (EZH2). The roles of NEAT1 in the regulation of oxaliplatin resistance to GC are in part by ameliorating the inhibitory effect of miR-26 on EZH2.
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http://dx.doi.org/10.1002/cbin.11245 | DOI Listing |
BMC Cancer
January 2025
Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Background: Colorectal cancer (CRC) is a common gastrointestinal cancer, and even though oxaliplatin chemotherapy is effective, there is a high likelihood of relapse, indicating the presence of oxaliplatin-resistant CRC. Therefore, it is crucial to comprehend the molecular mechanisms of oxaliplatin resistance and develop effective strategies to counter drug resistance. Numerous studies have demonstrated the close association between microRNAs (miRNAs) and drug resistance in CRC.
View Article and Find Full Text PDFBiomolecules
December 2024
Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK.
Cancer stem cells (CSCs) play a key role in non-small cell lung cancer (NSCLC) chemoresistance and metastasis. In this study, we used two NSCLC cell lines to investigate the regulating effect of hypoxia in the induction and maintenance of CSC traits. Our study demonstrated hypoxia-induced stemness and chemoresistance at levels comparable to those in typical CSC sphere culture.
View Article and Find Full Text PDFJ Nat Med
January 2025
College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea.
Cancer Med
January 2025
Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, People's Republic of China.
Fundam Clin Pharmacol
February 2025
Department Oncology Radiotherapy, The Third Affiliated Hospital of Wenzhou Medical University, Rui'an People Hospital, Zhejiang, China.
Background: The development of resistance to oxaliplatin is a multifaceted process, often involving modifications in drug transport, DNA repair mechanisms, and the ability of cells to evade drug-induced apoptosis.
Objective: To evaluate whether knocking down RFC3 promotes the sensitivity of colorectal cancer (CRC) cells to oxaliplatin, potentially offering a new approach to combat drug resistance.
Methods: siRNA-mediated knockdown of RFC3 was employed in colorectal cancer cell lines to assess the impact on oxaliplatin responsiveness.
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