Study On The Function And Mechanism Of Linc-ROR And P53 In Regulating Lung Cancer Stem Cell Stemness By MiRNA-145 Targets Oct4 And Sox2

ObjectiveTo investigate the effects of linc-ROR and tumor suppressor gene p53 on the expression of stem cell related genes Oct4 and Sox2 by mi RNA-145 and lung cancer proliferation and migration.Methods80 patients with lung adenocarcinoma(LAC)and the corresponding adjacent tissues were collected from thoracic surgery for removal from thoracic surgery in the hospital from March 2014 to December 2015.Eight patients with non-small cell lung cancer tissue samples and 60 paracancerous tissue samples were collected and the prognosis data were collected.The expression levels of miR-145,linc-ROR and p53 mRNA were detected by Real-time PCR.The expression levels of p53 protein,OCT4 protein and Sox2 protein were detected by Western Blot.CD44 + CD133 + lung cancer stem cells were isolated from lung cancer cell line A549 by flow cytometry.The binding sequence of miR-145 to OCT4 and Sox2 was predicted by Miranda database.OCT4 was identified as a miR-145 target molecule in A549 cells by fluorescence double reporter gene.ResultsMiR-145 expression was low in LAC tissues and p53 promotes the expression of miR-145 in lung cancer stem cells of A549 cells.MiR-145 mimics can inhibit the expression of OCT4 in A549 cells,and transfection of mi R-145 inhibitors can further increase the expression of OCT4 and reverse the inhibitory effect of p53 on the stem cell characteristics of A549 cells.In non-small cell lung cancer(NSCLC)tissue samples and lung cancer stem cells(LCSC),miR-145 levels were down-regulated while p53 and lincRNA ROR(ROR)were up-regulated.MiR-145 expression was negatively correlated with ROR expression.In addition,for NSCLC patients,low expression of p53,miR-145,and ROR overexpression indicate a poor prognosis in patients.ROR silencing can induce p53 protein translation,while silencing of p53 can downregulate the abundance of ROR.Finally,silencing ROR in lung cancer stem cells and lung cancer cells(LCCs)can inhibit cell proliferation,migration and invasion,and reduce tumor growth and metastasis in mice.ConclusionIn non-small cell lung cancer,linc-ROR and ROR regulates each other and inhibites the expression of miR-145 and up-regulates the expression of miR-145 targets Oct4 and Sox2,increasing the proportion of lung cancer stem cells and promoting the proliferation and invasion of lung cancer cells and lung cancer development.