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LINC00115表达升高通过JAK/STAT通路调节与侵袭性子宫内膜癌表型相关。

Elevated LINC00115 expression correlates with aggressive endometrial cancer phenotypes via JAK/STAT pathway modulation.

作者信息

Zhao Zheqi, Liu Yangyang, Wang Mengyao, Wei Aiwu

机构信息

Department of Reproductive Medicine, The First Affiliated Hospital of Henan University of CM, No. 19, Renmin Road, Jinshui District, Zhengzhou City, Henan Province, China.

The First Clinical Medical College of Henan University of Traditional Chinese Medicine, No. 19, Renmin Road, Jinshui District, Zhengzhou City, Henan Province, China.

出版信息

Hum Mol Genet. 2025 Jan 7. doi: 10.1093/hmg/ddae194.

Abstract

This study systematically explores the oncogenic role of the long non-coding RNA (lncRNA) LINC00115 in endometrial cancer (EC) and reveals its unique mechanism in promoting proliferation, invasion, and metastasis via the JAK/STAT signaling pathway. LINC00115 is significantly upregulated in EC tissues and closely associated with advanced TNM staging and lymph node metastasis. Functional assays showed that knockdown of LINC00115 suppressed EC cell proliferation, invasion, and metastasis, while overexpression enhanced these malignant behaviors. In vivo models confirmed that LINC00115 overexpression accelerates tumor growth and metastasis. Our study is the first to identify LINC00115 as a key activator of the JAK/STAT pathway through direct interaction with KH-type Splicing Regulatory Protein (KHSRP), a previously unrecognized mechanism in EC. This finding provides new insights into lncRNA-mediated signaling regulation and highlights LINC00115 as a novel biomarker and promising therapeutic target for EC, offering a theoretical basis for developing targeted therapies.

摘要

本研究系统地探讨了长链非编码RNA(lncRNA)LINC00115在子宫内膜癌(EC)中的致癌作用,并揭示了其通过JAK/STAT信号通路促进增殖、侵袭和转移的独特机制。LINC00115在EC组织中显著上调,且与晚期TNM分期和淋巴结转移密切相关。功能实验表明,敲低LINC00115可抑制EC细胞的增殖、侵袭和转移,而过表达则增强这些恶性行为。体内模型证实,LINC00115过表达加速肿瘤生长和转移。我们的研究首次通过与KH型剪接调节蛋白(KHSRP)直接相互作用,确定LINC00115是JAK/STAT通路的关键激活因子,这是EC中一种此前未被认识的机制。这一发现为lncRNA介导的信号调节提供了新的见解,并突出了LINC00115作为EC的新型生物标志物和有前景的治疗靶点,为开发靶向治疗提供了理论基础。

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