View related articlesView Crossmark data Citing articles: 1 View citing articles CYLD expression in dendritic cells involved in the immunoregulation of pulmonary adenocarcinoma via NF-jB pathway
The purpose of the current study was to define the role of MAX interactor 1 (Mxi1) in the pathogenesis of lung cancer and its underlying molecular mechanism. Bioinformatics analysis was performed to identify important regulatory pathway related to lung cancer. Dual luciferase reporter and ChIP assays were adopted to validate the interaction among Mxi1, miR-300 and KLF9. Loss- and gain-of-function studies were conducted to determine the roles of Mxi1, miR-300, and KLF9 in cell proliferation, migration, and invasion in vitro and their effects on myeloid-derived suppressor cell (MDSC) recruitment in vivo. Mxi1 was poorly expressed in lung cancer tissues and cells and its poor expression was associated with poor prognosis. Mxi1 inhibited miR-300 by suppressing its transcription. miR-300 suppressed the expression of KLF9, and KLF9 negatively regulated GADD34 expression in lung cancer cells. Mxi1 or KLF9 elevation or miR-300 repression inhibited lung cancer cell proliferation, as evidenced by reduced Ki67 and PCNA expression, and lowered invasion and migration. In vivo findings revealed that silencing KLF9 induced tumor growth by enhancing MDSC-mediated immunosuppression through upregulation of GADD34. Collectively, these findings suggest that Mxi1 can inhibit lung cancer progression by regulating the miR-300/KLF9 axis and GADD34-mediated immunosuppression.
Recently, long noncoding RNAs (lncRNAs) have been identified as novel and potential therapeutic targets in various cancer types. Nonetheless, the levels and biological effects of lncRNAs in non-small cell lung cancer (NSCLC) remain largely unknown. In this study, we aimed to identify the effects of lncRNA-LINC01260 throughout the progression of NSCLC and explore the underlying mechanism. Methods: Quantitative real-time PCR (qRT-PCR) and Western blot were performed to measure LINC01260, miR-562, and CYLD expression and protein levels. Luciferase reporter assay was employed to investigate the relationship between LINC01260 and miR-562, and miR-562 and CYLD, respectively. The viability and migration of cells were evaluated using CCK-8, colony formation, and transwell assays. The effects of LINC01260 were identified through tumorigenesis in vivo. ELISA was performed to detect the activity of NF-κB and p65 expression. Results: In NSCLC tissues and cell lines, LINC01260 expression was downregulated, which corresponded to a lower survival rate of patients with NSCLC. Knockdown of LINC01260 accelerated the proliferation, colony formation, and migration of NSCLC cells. Moreover, downregulation of LINC01260 inhibited apoptosis of NSCLC cells by regulating the expression of Bcl-2 and Bax proteins in vitro. In vivo, the downregulation of LINC01260 promoted tumor growth. miR-562 was identified as the target gene of LINC01260, which was upregulated in NSCLC tumors. Furthermore, CYLD was identified as the target gene of miR-562. The effects of LINC01260 were exerted by regulating CYLD via sponging miR-562. ELISA confirmed that the upregulation of CYLD inhibited NF-κB activity; however, the co-transfection of sh-LINC01260 partly reversed the inhibition. Additionally, CYLD reduced p65 expression; however, downregulation of LINC01260 slightly increased the expression level. Conclusion: This study revealed a novel LINC01260/miR-562/CYLD/NF-κB pathway in the pathogenesis of NSCLC and suggested a potential therapeutic target for NSCLC.
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