CDH3-AS1 antisense RNA enhances P-cadherin translation and acts as a tumor suppressor in melanoma.

IF 6.9 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-10-01 DOI:10.1016/j.celrep.2025.116362

Manon Chadourne, Crystal Griffith, Neel Jasani, Xiaonan Xu, Emily Brennan, Olga Vera, Nicol Mecozzi, Kaizhen Wang, Alex M Jaeger, Florian A Karreth

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引用次数: 0

Abstract

Thousands of regulatory non-coding RNAs (ncRNAs) have been annotated, yet their roles in gene regulation and cancer progression remain unclear. Mapping the landscape of ncRNA expression during melanoma progression revealed that ncRNAs represented nearly half of the deregulated genes, with antisense RNAs (asRNAs) comprising a large portion. CDH3-AS1, the most downregulated asRNA, overlaps the CDH3 gene, which encodes P-cadherin, a key cell adhesion protein that is reduced in melanoma. Overexpression of CDH3-AS1 increased cell aggregation and reduced xenograft tumor growth, mimicking the effects of CDH3. CDH3-AS1 interacted with CDH3 mRNA, increased ribosome occupancy, and enhanced P-cadherin translation through a mechanism resembling SINEB2 sequence to up-regulate translation (SINEUP)-mediated translational control. asRNAs complementary to 5' UTRs generally increase the ribosome occupancy of their cognate mRNAs, suggesting broader translational control through this mechanism. This study revealed CDH3-AS1-mediated enhancement of P-cadherin translation as a tumor-suppressive axis in melanoma and highlighted the broader potential of asRNAs as regulators of protein translation.

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CDH3-AS1反义RNA增强P-cadherin翻译并在黑色素瘤中起抑瘤作用。

数以千计的调节性非编码rna （ncrna）已被标注，但它们在基因调控和癌症进展中的作用仍不清楚。绘制黑色素瘤进展过程中ncRNA的表达图谱显示，ncRNA代表了近一半的非调控基因，其中反义rna （asrna）占很大一部分。CDH3- as1是最下调的asRNA，与编码p -钙粘蛋白的CDH3基因重叠，p -钙粘蛋白是一种关键的细胞粘附蛋白，在黑色素瘤中减少。CDH3- as1的过表达增加了细胞聚集，减少了异种移植肿瘤的生长，类似于CDH3的作用。CDH3- as1通过类似SINEB2序列的机制与CDH3 mRNA相互作用，增加核糖体占用，增强P-cadherin翻译，上调翻译（SINEUP）介导的翻译控制。与5' utr互补的asRNAs通常会增加其同源mrna的核糖体占用率，表明通过这种机制可以更广泛地控制翻译。本研究揭示了cdh3 - as1介导的p -钙粘蛋白翻译增强在黑色素瘤中作为肿瘤抑制轴，并强调了asrna作为蛋白质翻译调节因子的更广泛潜力。

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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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.