Mechanism of long non-coding RNA SATB2-AS1 inhibiting progression of lung adenocarcinoma
Objective To investigate the effect of long non-coding RNA(lncRNA)antisense transcript of SATB2 protein(SATB2-AS1)on the biological function of lung adenocarcinoma cells and its mechanism.Methods Tumor tissues and adjacent tissues from 25 patients with lung adenocarcinoma were collected to detect the expression of SATB2-AS1.Then,the overexpression vector of lncRNA SATB2-AS1(pcDNA-SATB2-AS1)and shRNA or shRNA of IGF2BP2(sh-SATB2-AS1;sh-IGF2BP2)and/or shRNA of SLC7A11(sh-SLC7A11)were transfected into lung adenocarcinoma cell A549.RIP assay was used to estimate the binding of IGF2BP2 protein to SATB2-AS1 or SLC7A11 mRNA,respectively;CCK-8 and Transwell assay were used to detect the proliferation and invasion ability of lung adenocarcinoma cells;RT-qPCR and Western blot assay were used to detect gene expression and protein expression,respectively.Results Compared with adjacent tissues and human bronchial epithelial cell BEAS-2B,the expression of SATB2-AS1 was significantly down-regulated in tumor tissues of patients with lung adenocarcinoma and lung adenocarcinoma cells(P<0.01).Overexpression of SATB2-AS1 significantly inhibited the proliferation and invasion of A549 cells,while silencing SATB2-AS1 significantly promoted the cell proliferation and invasion(P<0.05).Moreover,overexpression of SATB2-AS1 significantly reduced Fe2+concentration,reactive oxygen species(ROS)level,and malondialdehyde(MDA)content in A549 cells(P<0.01),and increased glutathione(GSH)content,the expression of SLC7A11 and GPX4 which were the key proteins of ferroptosis(P<0.01).Meanwhile,SATB2-AS1 significantly promoted IGF2BP2 protein binding to SLC7A11 mRNA by binding to IGF2BP2 protein,and reduced the stability of SLC7A11 mRNA(P<0.01).Silencing SLC7A11 significantly reversed the effects of silencing SATB2-AS1 on A549 cells.Conclusion LncRNA SATB2-AS1 destabilizes SLC7A11 mRNA by recruiting IGF2BP2 protein,induces the ferroptosis of lung adenocarcinoma cells,inhibits the cell proliferation and invasion,and thus inhibits the progression of lung adenocarcinoma.
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