KIF26B-AS1 Regulates TLR4 and Activates the TLR4 Signaling Pathway to Promote Malignant Progression of Laryngeal Cancer

Abstract

Laryngeal cancer is one of the highest incidence, most prevalently diagnosed head and neck cancers, making it critically necessary to probe effective targets for laryngeal cancer treatment. Here, real-time quantitative reverse transcription PCR (qRT-PCR) and western blot analysis were used to detect gene expression levels in laryngeal cancer cell lines. Fluorescence in situ hybridization (FISH) and subcellular fractionation assays were used to detect the subcellular location. Functional assays encompassing Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), transwell and wound healing assays were performed to examine the effects of target genes on cell proliferation and migration in laryngeal cancer. The in vivo effects were proved by animal experiments. RNA-binding protein immunoprecipitation (RIP), RNA pulldown and luciferase reporter assays were used to investigate the underlying regulatory mechanisms. The results showed that KIF26B antisense RNA 1 (KIF26B-AS1) propels cell proliferation and migration in laryngeal cancer and regulates the toll-like receptor 4 (TLR4) signaling pathway. KIF26B-AS1 also recruits FUS to stabilize TLR4 mRNA, consequently activating the TLR4 signaling pathway. Furthermore, KIF26B-AS1 plays an oncogenic role in laryngeal cancer via upregulating TLR4 expression as well as the FUS/TLR4 pathway axis, findings which offer novel insight for targeted therapies in the treatment of laryngeal cancer patients.

Prognostic and clinicopathological significance of TLR4 expression in patients with breast cancer: a meta-analysis

“…The mechanisms by which TLR4 promotes metastasis include the facilitation of an epithelialmesenchymal transition (EMT) and the elevation of cytokines (IL-6, IL-10) that boost matrix metalloproteinase (MMP2 and MMP9) expression (24). In laryngeal cancer, KIF26B antisense RNA 1 regulates TLR4 and activates the TLR4 signaling pathway to promote malignant progression (25). In ovarian cancer, LPS induced the activation of TLR4, up-regulated osteopontin, and increased the malignant phenotype of ovarian cancer cells (26).…”