Function And Molecular Mechanism Of MetaLnc9 And MiRNA-10a In Lung Cancer

Lung cancer is one of the most common malignant tumors in the world,metastasis is the main cause of death in lung cancer patients.The metastatic cascade is a complex and multistep process with many potential barriers.Recent evidence has shown that Non-coding RNAs(ncRNAs)are involved in carcinogenesis and tumor progression.However,the precise regulation mechanism of 1ncRNAs on cancer metastasis is still unclear.We used weakly invasive cell line SPC-A-1 and highly invasive cell subline SPC-A-lsci established by our own lab as study subj ects and take advantage of human genome expression array analysis to screen metastasis related ncRNAs.we demonstrated that the up-regulation and function of MetaLnc9 and miRNA-10a in NSCLC metastasis and the expression of these ncRNAs was overexpressed in NSCLC compared with corresponding nontumorous tissues.MetaLnc9 and miRNA-10a expression were significantly associated with tumor node metastasis(TNM)and lymph node metastasis.Furthermore,functional assays showed that the overexpression of MetaLnc9 and miRNA-10a promoted NSCLC cell migration and invasion.Mechanistically,MetaLnc9 interacts with phosphoglycerate kinase 1(PGK1)and prevents its ubiquitination in NSCLC cells,activating oncogenic AKT/mTOR oncogenic signaling pathway.Moreover,MetaLnc9 interacts with P54nrb/NonO(NONO)and participates in the cyclic AMP-responsive element-binding protein(CREB)/CREB-regulated transcription coactivator(CRTC)-mediated transcription,resulting in a positive feedback loop.In addition,we also demonstrated that miR-10a contributes to NSCLC carcinogenesis by targeting the phosphatase and tension homologue(PTEN)and activates the AKT/ERK signaling pathway.Collectively,our study offers mechanistic insights into the oncogenic roles of MetaLnc9 and miRNA-10a,and the pivotal effects of MetaLnc9 and miRNA-10a as biomarkers and therapeutic targets for NSCLC metastasis.