Long Non-coding RNA LINC01426 Contributes to the Malignant Behaviors of NSCLC Via Acting As a Sponge for miR-143-3p

Abstract

Recently, long non-coding RNA (lncRNA) is proved to play critical roles in non-small cell lung cancer (NSCLC) progression. However, the detailed effects of LINC01426 in NSCLC and its functional mechanism remain unknown. The expression of LINC01426, microRNA-143-3p (miR-143-3p), and Ubiquitin-specific peptidase 28 (USP28) was assessed by quantitative real-time polymerase chain reaction (RT-qPCR). The colony-forming ability was determined by colony-forming assay. 5-ethynyl-2'-deoxyuridine (EdU) staining assay was performed to evaluate cell proliferation. The migrated and invaded abilities of cells were measured by transwell assays. Flow cytometry was used to examine cell apoptosis. The protein expression was analyzed by Western blot analysis. The glycolysis ability was analyzed by commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to confirm relationship among LINC01426, miR-143-3p, and USP28. A xenograft experiment was conducted to explore the effects of LINC01426 inhibition in vivo. Our results confirmed that LINC01426 and USP28 expression were increased, while miR-143-3p expression was decreased in NSCLC tissues and cells. Further functional experiments demonstrated that LINC01426 inhibition markedly impaired cell proliferation, migration, invasion, autophagy, and glycolysis while induced apoptosis in NSCLC cells, and LINC01426 derived malignant behaviors of NSCLC cells by sponging miR-143-3p. Additionally, LINC01426 regulated USP28 expression by sponging miR-143-3p. USP28 overexpression partly overturned the inhibitory effect of miR-143-3p on NSCLC progression. Consistently, silencing of LINC01426 significantly inhibited the growth of NSCLC tumor in vivo. LINC01426 accelerated the malignant progression of NSCLC. Mechanistically, LINC01426 acted as a competing endogenous RNA (ceRNA) for miR-143-3p to upregulate USP28 expression.

Keywords: LINC01426; NSCLC; USP28; lncRNA; miR-143-3p.