IGF2BP3 As a Prognostic Biomarker and Regulator of Metastasis in Merkel Cell Carcinoma

JID innovations : skin science from molecules to population health Pub Date : 2025-02-12 DOI:10.1016/j.xjidi.2025.100355

Yajie Yang , Jiwei Gao , Hao Shi , Harri Sihto , Sami Kilpinen , François Vilcot , Libuse Janská , Jakob Jeschonneck , Todor Cvetanovic , Anders Höög , Jan Siarov , John Paoli , C. Christofer Juhlin , Lisa Villabona , Catharina Larsson , Weng-Onn Lui

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Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer with frequent metastasis; however, effective treatment options for advanced disease are often lacking. In this study, we investigated the clinical significance and functional impact of IGF2 mRNA-binding protein 3 (IGF2BP3) in MCC. Our results revealed elevated IGF2BP3 expression in metastases compared to that in primary tumors. High IGF2BP3 levels in primary MCCs were associated with shorter disease-specific survival rates. In an MCC xenograft model, the lung metastases exhibited increased IGF2BP3 expression. Functional studies showed that IGF2BP3 primarily regulates MCC cell migration and invasion. We identified 281 direct RNA targets of IGF2BP3 with enriched functions linked to metastasis-related processes, and several targets overlapped with genes differentially expressed between MCC primary tumors and metastases, implying that IGF2BP3 and its targets contribute to tumor progression. Inhibition or silencing of bromodomain-containing protein 4 reduced IGF2BP3 expression, suggesting that bromodomain-containing protein 4 is a potential regulator of IGF2BP3. Our study underscores the role of IGF2BP3 in MCC metastasis and its potential as a prognostic biomarker.

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梅克尔细胞癌（MCC）是一种侵袭性皮肤癌，经常发生转移；然而，晚期疾病往往缺乏有效的治疗方案。本研究调查了 IGF2 mRNA 结合蛋白 3（IGF2BP3）在 MCC 中的临床意义和功能影响。结果显示，与原发肿瘤相比，转移瘤中 IGF2BP3 的表达升高。原发性 MCC 中的高 IGF2BP3 水平与较短的疾病特异性生存率相关。在一个 MCC 异种移植模型中，肺转移瘤的 IGF2BP3 表达增加。功能研究表明，IGF2BP3 主要调控 MCC 细胞的迁移和侵袭。我们发现了281个IGF2BP3的直接RNA靶标，这些靶标的功能与转移相关过程有关，其中几个靶标与MCC原发肿瘤和转移灶之间差异表达的基因重叠，这意味着IGF2BP3及其靶标有助于肿瘤的进展。抑制或沉默含溴结构域蛋白4会降低IGF2BP3的表达，这表明含溴结构域蛋白4是IGF2BP3的潜在调控因子。我们的研究强调了IGF2BP3在MCC转移中的作用及其作为预后生物标志物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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