Exploring the Role of LINC00115 in Esophageal Squamous Cell Carcinoma: Insights Into JAK1/STAT3 Pathway Activation and Metastatic Potential.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with poor prognosis. This study aims to explore the molecular mechanisms underlying ESCC metastasis, particularly focusing on the role of the long noncoding RNA LINC00115, its interaction with the KHSRP protein, and the activation of the JAK1/STAT3 signaling pathway. Expression levels of LINC00115 were analyzed in 96 paired ESCC tumor and adjacent normal tissues using RT-qPCR. In vitro assays, including CCK-8, colony formation, wound healing, Transwell migration, and invasion assays, were performed on ESCC cell lines to assess the functional impact of LINC00115. In vivo experiments were conducted using nude mouse models to evaluate the tumorigenic and metastatic potential of LINC00115. RNA pull-down, mass spectrometry, and RNA immunoprecipitation assays were used to identify and validate LINC00115 interaction partners. The involvement of the JAK1/STAT3 signaling pathway was confirmed through qPCR and Western blot analysis. LINC00115 was found to be upregulated in ESCC tissues and associated with advanced TNM staging and lymph node metastasis. Its silencing appeared to suppress ESCC cell proliferation, migration, and invasion in vitro and reduce tumor growth and metastasis in vivo. Mechanistically, LINC00115 may interact with KHSRP in the cytoplasm and potentially activate the JAK1/STAT3 signaling pathway involved in ESCC progression. This study suggests that LINC00115 may promote ESCC progression via the JAK1/STAT3 pathway through KHSRP interaction. Further validation is needed, and it should be considered a candidate marker rather than a therapeutic target.