Scholarlink

Background <p>Gastric cancer (GC) is the fourth most common cause of cancer-related mortality and the fifth most common cancer worldwide. Despite efforts, the identification of biomarkers and new therapeutic approaches for GC remains elusive. Recent studies have begun to reveal the role of N6-adenosine methylation (m<sup>6</sup>A) in the regulation of gene expression. </p> Methods <p>The expression of the reader YT521-B homology domain-containing family 3 (YTHDF3) in GC was assessed in 331 patients using immunohistochemistry. GC cell lines depleted of YTHDF3 using CRISPR-Cas9 were evaluated for migration, metastasis, orientation of the mitotic spindle, and response to paclitaxel. The association between YTHDF3 and <i>EZRIN</i> (<i>EZR</i>) mRNA was shown using RNA sequencing, immunofluorescence, real-time PCR, and RNA immunoprecipitation. The single-base elongation- and ligation-based qPCR amplification (SELECT) method was used to map m<sup>6</sup>A in the <i>EZR</i> transcript. </p> Results <p>YTHDF3 was significantly overexpressed in GC, and high levels of YTHDF3 were predictive of the response to chemotherapy. In GC cell lines, YTHDF3 was the most highly expressed reader protein. YTHDF3 depletion impaired cytoskeleton organization, cell migration and metastasis, and orientation of the mitotic spindle, leading to an increased response to paclitaxel. <i>EZR</i> was one of the downregulated targets in the <i>YTHDF3</i> knockout cell models and was associated with the observed phenotype.</p> Conclusion <p>YTHDF3 contributes to cell motility and response to paclitaxel in GC cell lines, at least in part through EZR regulation. The YTHDF3–EZR regulatory axis is a novel molecular player in GC, with clinical relevance and potential therapeutic utility.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The RNA-binding protein YTHDF3 affects gastric cancer cell migration and response to paclitaxel by regulating EZRIN

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月14日

查看全文
  • Patrícia Mesquita,
  • Alexandre Coelho,
  • Ana S. Ribeiro,
  • Luís F. C. Póvoas,
  • Catarina de Oliveira,
  • Nelson Leça,
  • Sara Silva,
  • Diana Ferreira,
  • Diana Pádua,
  • Ricardo Coelho,
  • Carmen Jerónimo,
  • Joana Paredes,
  • Carlos Conde,
  • Bruno Pereira,
  • Raquel Almeida

摘要

Background

Gastric cancer (GC) is the fourth most common cause of cancer-related mortality and the fifth most common cancer worldwide. Despite efforts, the identification of biomarkers and new therapeutic approaches for GC remains elusive. Recent studies have begun to reveal the role of N6-adenosine methylation (m6A) in the regulation of gene expression.

Methods

The expression of the reader YT521-B homology domain-containing family 3 (YTHDF3) in GC was assessed in 331 patients using immunohistochemistry. GC cell lines depleted of YTHDF3 using CRISPR-Cas9 were evaluated for migration, metastasis, orientation of the mitotic spindle, and response to paclitaxel. The association between YTHDF3 and EZRIN (EZR) mRNA was shown using RNA sequencing, immunofluorescence, real-time PCR, and RNA immunoprecipitation. The single-base elongation- and ligation-based qPCR amplification (SELECT) method was used to map m6A in the EZR transcript.

Results

YTHDF3 was significantly overexpressed in GC, and high levels of YTHDF3 were predictive of the response to chemotherapy. In GC cell lines, YTHDF3 was the most highly expressed reader protein. YTHDF3 depletion impaired cytoskeleton organization, cell migration and metastasis, and orientation of the mitotic spindle, leading to an increased response to paclitaxel. EZR was one of the downregulated targets in the YTHDF3 knockout cell models and was associated with the observed phenotype.

Conclusion

YTHDF3 contributes to cell motility and response to paclitaxel in GC cell lines, at least in part through EZR regulation. The YTHDF3–EZR regulatory axis is a novel molecular player in GC, with clinical relevance and potential therapeutic utility.