SIX5-activated LINC01468 promotes lung adenocarcinoma progression by recruiting SERBP1 to regulate SERPINE1 mRNA stability and recruiting USP5 to facilitate PAI1 protein deubiquitylation

Abstract

Increasing research has uncovered the involvement of long noncoding RNAs (lncRNAs) in the progression of multiple cancers including lung adenocarcinoma (LUAD). RT-qPCR and western blot were done to measure RNAs and proteins. Functional assays assessed LUAD cell biological behaviors under knockdown or overexpression of LINC01468, SIX5, SERBP1 or SERPINE1, and the specific function of those genes in regulating LUAD progression was evaluated via animal experiments. Supported by bioinformatics analysis, the interaction among genes was verified via mechanism assays. Upregulation of LINC01468 in LUAD tissues and cells as well as its association with poor clinical outcome was predicted. LINC01468, transcriptionally activated by SIX5, could strengthen proliferative, migratory and invasive abilities of LUAD cells. The oncogenic role of LINC01468 was further validated via animal experiments. SIX5 was a positive transcription regulator of LINC01468 and could exacerbate LUAD cell malignant behaviors. LINC01468 could recruit SERBP1 to enhance SERPINE1 mRNA stability and interact with USP5 to affect PAI1 protein ubiquitination. The oncogenic role of SERBP1 and SERPINE1 was also confirmed. Rescue experiments finally verified LINC01468 modulated proliferation, migration and invasion of LUAD cells via upregulation of SERPINE1. Our observations could contribute to deeper understanding of LUAD.