替代拼接MDM2-ALT2异型在逆皮质脂肉瘤中的瘤功能
Fernanda Costas C de Faria1, Safiya Khurshid2, Patricia Sarchet1
1The James Comprehensive Cancer Center, Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
International journal of molecular sciences
|January 8, 2025
概括
替代拼接的MDM2-ALT2转录可能会驱动回皮质脂肪瘤 (RPLPS) 的进展. 这项研究发现,MDM2-ALT2在RPLPS中受到上调,并通过AKT通路促进细胞增殖和侵入.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 复原皮质脂肪肉瘤 (RPLPS) 是一种常见的软组织肉瘤 (STS),复发率很高.
- 区分良好的和不区分的亚型 (WDLPS/DDLPS) 通常具有MDM2基因放大.
- 在RPLPS中替代拼接的MDM2转录的作用仍未得到充分研究.
研究的目的:
- 评估RPLPS患者组织中的MDM2-ALT2表达.
- 为了研究MDM2-ALT2异型在非分化脂肪瘤 (DDLPS) 细胞系中的体外生物功能.
主要方法:
- 使用BaseScopeTM和定量PCR (qPCR) 来测量RPLPS组织中的MDM2-FL和MDM2-ALT2表达,而不是与瘤相邻的正常组织 (NAT).
- 在DDLPS细胞系中过度表达的MDM2-FL或MDM2-ALT2,以评估扩散,迁移和入侵.
- 通过将MDM2-ALT2过度表达与AKT沉默相结合,研究了AKT通路的作用.
主要成果:
- 与NAT相比,RPLPS组织中的MDM2-全长 (MDM2-FL) 和MDM2-ALT2在RPLPS组织中被上调.
- 在DDLPS细胞中MDM2-FL或MDM2-ALT2的过度表达增加了增殖,迁移和入侵.
- 在MDM2过度表达的情况下,观察到p-AKT,mTOR,p70S6K,MMP2和cJun的蛋白质水平升高.
- AKT抑制抵消了MDM2-ALT2诱导的p-p70S6K和MMP2的增加,减少了增殖和迁移.
结论:
- 在RPLPS中,MDM2-ALT2被上调,并有助于瘤的进展.
- MDM2-ALT2促进RPLPS细胞的增殖和入侵,部分通过AKT/mTOR信号通路.
- MDM2-ALT2代表了RPLPS的潜在治疗标.
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