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

Hum Mol Genet. 2025 Jan 7:ddae194. doi: 10.1093/hmg/ddae194. Online ahead of print.

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.

Keywords: LINC00115; endometrial cancer; tumor biomarker; tumor invasion and migration; tumor proliferation.