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Background <p>Due to high heterogeneity, diagnosing MDS can be challenging. Consequently, investigating its pathogenesis and progression mechanisms, and seeking novel targets for diagnosis and treatment, are critical issues that require urgent attention. This study aimed to investigate whether <i>LRRFIP1</i> might contribute to MDS pathogenesis by modulating the Wnt/β-catenin signaling pathway.</p> Methods <p>In MDS cell lines, mRNA transcriptome sequencing and Dual luciferase reporter gene assays were employed to assess Wnt/β-catenin signaling pathway activity. To explore the biological characteristics of MDS cell lines, CCK8, Annexin-V APC/7-AAD and Annexin V-FITC/PI double staining and fluorescence TUNEL assay, and PI single staining were used.</p> Results <p>In MDS cell lines, proliferation was notably higher in <i>LRRFIP1</i>-overexpressing cells compared to silenced ones, while cell apoptosis was lower in the former. mRNA transcriptome sequencing revealed <i>LRRFIP1</i>'s involvement in modulating the Wnt/β-catenin signaling pathway. <i>LRRFIP1</i> was found to positively regulate Wnt/β-catenin pathway activity, and synergy between <i>LRRFIP1</i> and <i>Dvl</i> was observed in enhancing canonical Wnt signaling. <i>LRRFIP1</i> overexpression significantly upregulated key genes in Wnt signaling pathway (such as <i>β-catenin</i>, <i>Dvl2</i>, <i>Dvl3</i> and <i>Wnt</i>) at the mRNA level, and notably upregulated non-phosphorylated β-catenin at the protein level. Moreover, BCL-2 and CyclinD1 protein expression was significantly higher in <i>LRRFIP1</i>-overexpressing cells compared to silenced ones, with even greater expression observed in <i>LRRFIP1/Dvl3</i> co-overexpressing cells.</p> Conclusions <p><i>LRRFIP1</i> can promote the proliferation of MDS cells and inhibit apoptosis, and <i>LRRFIP1</i> and <i>Dvl</i> can synergistically enhance the activity of the Wnt/β-catenin signaling pathway in MDS, thus providing evidence for <i>LRRFIP1</i>'s involvement in the pathogenesis of MDS.</p>

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LRRFIP1 enhances the Wnt/β-catenin pathway by binding to DVLs in myelodysplastic syndrome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月26日

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  • Xiaoli Zhao,
  • Yutian Lei,
  • Han Zhu,
  • Wenyi Shen,
  • Sixuan Qian,
  • Jianyong Li,
  • Yu Zhu

摘要

Background

Due to high heterogeneity, diagnosing MDS can be challenging. Consequently, investigating its pathogenesis and progression mechanisms, and seeking novel targets for diagnosis and treatment, are critical issues that require urgent attention. This study aimed to investigate whether LRRFIP1 might contribute to MDS pathogenesis by modulating the Wnt/β-catenin signaling pathway.

Methods

In MDS cell lines, mRNA transcriptome sequencing and Dual luciferase reporter gene assays were employed to assess Wnt/β-catenin signaling pathway activity. To explore the biological characteristics of MDS cell lines, CCK8, Annexin-V APC/7-AAD and Annexin V-FITC/PI double staining and fluorescence TUNEL assay, and PI single staining were used.

Results

In MDS cell lines, proliferation was notably higher in LRRFIP1-overexpressing cells compared to silenced ones, while cell apoptosis was lower in the former. mRNA transcriptome sequencing revealed LRRFIP1's involvement in modulating the Wnt/β-catenin signaling pathway. LRRFIP1 was found to positively regulate Wnt/β-catenin pathway activity, and synergy between LRRFIP1 and Dvl was observed in enhancing canonical Wnt signaling. LRRFIP1 overexpression significantly upregulated key genes in Wnt signaling pathway (such as β-catenin, Dvl2, Dvl3 and Wnt) at the mRNA level, and notably upregulated non-phosphorylated β-catenin at the protein level. Moreover, BCL-2 and CyclinD1 protein expression was significantly higher in LRRFIP1-overexpressing cells compared to silenced ones, with even greater expression observed in LRRFIP1/Dvl3 co-overexpressing cells.

Conclusions

LRRFIP1 can promote the proliferation of MDS cells and inhibit apoptosis, and LRRFIP1 and Dvl can synergistically enhance the activity of the Wnt/β-catenin signaling pathway in MDS, thus providing evidence for LRRFIP1's involvement in the pathogenesis of MDS.