LINC01559 promotes lung adenocarcinoma metastasis by disrupting the ubiquitination of VIM

Abstract

Background: As the predominant proportion of lung cancer, lung adenocarcinoma (LUAD) has emerged as a formidable malignancy that poses a substantial menace to human health. Numerous studies have demonstrated the undeniable involvement of long non-coding RNAs (lncRNAs) in tumorigenesis and tumor progression. Our investigation aims to elucidate the functional role and intrinsic molecular mechanism of LINC01559 in LUAD metastasis. Methods: The expression and prognosis of LINC01559 in LUAD were analyzed from the database. Quantitative real‐time PCR (qRT-PCR) and In Situ Hybridization (ISH) were performed to detect the expression level of LINC01559 in LUAD cell lines and tissues. With RNA interference (RNAi) technology, the biological function of LINC01559 in LUAD cell lines was clarified through transwell assay. Tail vein injection model was established to observe the effect of LINC01559 on LUAD metastasis in vivo. RNA pull down and RNA immunoprecipitation (RIP) were utilized to explore the binding proteins of LINC01559. The rescue experiment was conducted to investigate the role of LINC01559 in promoting LUAD metastasis through vimentin (VIM). The molecular mechanism underlying the regulation of VIM by LINC01559 was elucidated using CHX-chase and ubiquitination assays. Results: LINC01559 exhibited conspicuous upregulation in both LUAD tissues and cell lines, and was identified as a prognostic risk factor for patients with LUAD. Notably, knockdown of LINC01559 expression significantly inhibited the migration and invasion capabilities of LUAD cells. In vivo assay revealed that knockdown of LINC01559 curbed lung metastasis of LUAD. Molecular mechanism studies unveiled that LINC01559 interacted with VIM and modulated its protein level. Further investigations suggested that LINC01559 promoted LUAD metastasis by impeding the ubiquitination-mediated degradation of VIM. Conclusions: Our results demonstrated that LINC01559 played a crucial role in fostering LUAD metastasis by stabilizing the VIM protein, which suggested that LINC01559 might be a potential therapeutic target for inhibiting LUAD metastasis.