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<p>Chemoresistance leads to poor outcomes of patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been demonstrated as novel gene modulators in various carcinomas and chemoresistance. Our study aimed to investigate the role and underlying modulatory mechanism of lncRNA MATN1-AS1 in GC chemoresistance. CCK-8, flow cytometry, and Transwell assays were performed to explore the influence of the MATN1-AS1/microRNA (miR)-518b/zinc finger protein 281 (ZNF281) axis on the half inhibition concentration (IC50) to oxaliplatin (OXA), apoptosis, migration, and invasion of OXA-resistant GC cells. Dual-luciferase reporter assay was conducted to confirm the target association between miR-518b and MATN1-AS1 (or ZNF281). Xenograft mouse models were established to confirm the role of MATN1-AS1 silencing&#xa0;in vivo.&#xa0;The expression of MATN1-AS1, miR-518b, ZNF281, and&#xa0;multidrug&#xa0;resistance-related&#xa0;genes was detected through RT-qPCR and western blotting. MATN1-AS1 expression was upregulated in OXA-resistant GC tissues and cell lines versus OXA-sensitive tissues and parental cell lines. MATN1-AS1 depletion significantly inhibited the IC50 value of OXA, cell migration, invasion, and drug resistance but promoted cell apoptosis in OXA-resistant GC cells. Additionally, MATN1-AS1 upregulated ZNF281 expression by sponging miR-518b in OXA-resistant GC cells. Inhibiting miR-518b or overexpressing ZNF281 antagonized the effects of MATN1-AS1 silencing on OXA resistance of GC cells. Upregulation of ZNF281 abrogated the suppressive effects of miR-518b overexpression on OXA resistance of GC cells. Moreover, MATN1-AS1 knockdown suppressed tumor growth, OXA resistance, and Ki-67 expression in xenograft mouse models. MATN1-AS1 promotes OXA resistance of GC cells by enhancing ZNF281 expression via sequestration of miR-518b, shedding new light on the chemoresistance of GC.</p>

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Long noncoding RNA MATN1-AS1 contributes to oxaliplatin resistance of gastric cancer cells through miR-518b/ZNF281 axis

  • 期刊论文

  • 发表日期：

    2025年3月12日

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  • Xiuhuan Qiu,
  • Licheng Zhang,
  • Fengying Guo,
  • Ruixiang Guo

摘要

Chemoresistance leads to poor outcomes of patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been demonstrated as novel gene modulators in various carcinomas and chemoresistance. Our study aimed to investigate the role and underlying modulatory mechanism of lncRNA MATN1-AS1 in GC chemoresistance. CCK-8, flow cytometry, and Transwell assays were performed to explore the influence of the MATN1-AS1/microRNA (miR)-518b/zinc finger protein 281 (ZNF281) axis on the half inhibition concentration (IC50) to oxaliplatin (OXA), apoptosis, migration, and invasion of OXA-resistant GC cells. Dual-luciferase reporter assay was conducted to confirm the target association between miR-518b and MATN1-AS1 (or ZNF281). Xenograft mouse models were established to confirm the role of MATN1-AS1 silencing in vivo. The expression of MATN1-AS1, miR-518b, ZNF281, and multidrug resistance-related genes was detected through RT-qPCR and western blotting. MATN1-AS1 expression was upregulated in OXA-resistant GC tissues and cell lines versus OXA-sensitive tissues and parental cell lines. MATN1-AS1 depletion significantly inhibited the IC50 value of OXA, cell migration, invasion, and drug resistance but promoted cell apoptosis in OXA-resistant GC cells. Additionally, MATN1-AS1 upregulated ZNF281 expression by sponging miR-518b in OXA-resistant GC cells. Inhibiting miR-518b or overexpressing ZNF281 antagonized the effects of MATN1-AS1 silencing on OXA resistance of GC cells. Upregulation of ZNF281 abrogated the suppressive effects of miR-518b overexpression on OXA resistance of GC cells. Moreover, MATN1-AS1 knockdown suppressed tumor growth, OXA resistance, and Ki-67 expression in xenograft mouse models. MATN1-AS1 promotes OXA resistance of GC cells by enhancing ZNF281 expression via sequestration of miR-518b, shedding new light on the chemoresistance of GC.