miR-423-5p mediates LINC00886 regulation of ovarian cancer aggressiveness and immune evasion via the TLR4/Myd88/NF-κB/PD-L1 pathway.

Abstract

Background: Ovarian cancer has poor treatment outcomes. This study aims to explore the clinical importance of LINC00886 and its effects on cancer cell behavior in ovarian cancer, potentially offering a new therapeutic target.

Materials and methods: RT-qPCR was used to detect LINC00886 expression in ovarian cancer tissue, with analysis of clinicopathological data and prognosis based on LINC00886 expression levels. CCK-8, Traswell, and Annexin V-FITC/PI flow cytometry assays were used to evaluate the impact of molecular expression on cell viability, invasiveness, and apoptosis. RIP and dual luciferase reporter gene assays were used to validate interactions among miR-423-5p, LINC00886, and TLR4. Western blot analysis was conducted to investigate downstream signaling proteins, and ELISA was used to measure TNF-α and IFN-γ levels in cell co-culture.

Results: LINC00886 is upregulated in ovarian cancer tissues and cell lines, and its high expression is associated with poor prognosis; downregulating LINC00886 inhibits cell viability and invasiveness while inducing apoptosis. miR-423-5p is downstream of LINC00886 and upstream of TLR4. Inhibiting miR-423-5p reverses the suppressive effects of LINC00886 downregulation on cancer cell behavior. Overexpressing TLR4 enhances cellular processes. Furthermore, downregulating LINC00886 reduces the expression of TLR4, Myd88, phosphorylated NF-κB p65, and PD-L1, while increasing TNF-α and IFN-γ levels and enhancing CD8 + T cell antitumor activity, thereby reducing tumor cell immune escape.

Conclusions: LINC00886 drives ovarian cancer progression and immune escape through themiR-423-5p/TLR4/Myd88/NF-κB/PD-L1 axis, establishing its potential as both a prognostic biomarker and therapeutic target.