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SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression.

ABSTRACT: Structural maintenance of chromosome 4 (SMC4) is a core subunit of condensin complexes that mainly contributes to chromosome condensation and segregation. Our previous study demonstrated that the gene expression profile during lung development is of great values for the study of lung cancer. In this study, we identified SMC4 through co-expression network analysis and clique percolation clustering using genes that constant changes during four stages of lung development. Gene ontology and KEGG pathway enrichment analysis demonstrated that SMC4 is closely related to cell cycle, cell adhesion, and RNA processing in lung development and carcinogenesis. Moreover, SMC4 is overexpressed in lung adenocarcinoma tissues and acts as an independent prognostic factor. SMC4 knockdown significantly inhibits the proliferation and invasion of A549 cells. Furthermore, we found that SMC4 interacts with DDX46 (DEAD-box helicase 46). In conclusion, the pivotal role of SMC4 in lung development and carcinogenesis suggests that genes with a similar expression pattern to SMC4 in lung development may also contribute to lung cancer progression. The identification of genes that are essentially involved in development through a comparative study between development and cancer may be a practical strategy for discovering potential biomarkers and illuminating the mechanisms of carcinogenesis.

SUBMITTER: Zhang C

PROVIDER: S-EPMC5043270 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression.

Zhang Chengli C Kuang Manchao M Li Meng M Feng Lin L Zhang Kaitai K Cheng Shujun S

Scientific reports 20160930

Structural maintenance of chromosome 4 (SMC4) is a core subunit of condensin complexes that mainly contributes to chromosome condensation and segregation. Our previous study demonstrated that the gene expression profile during lung development is of great values for the study of lung cancer. In this study, we identified SMC4 through co-expression network analysis and clique percolation clustering using genes that constant changes during four stages of lung development. Gene ontology and KEGG pat ...[more]

PMID: 27687868

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Project description:BackgroundThe nuclear receptor REV-ERBα (nuclear receptor subfamily 1, Group D member 1, NR1D1) is one of the essential components of the circadian clock which modulates cell proliferation, glucose metabolism, inflammation, and many other biological processes. Modulation of these processes are also relevant to cancer development. Previous studies have suggested that activation of REV-ERBα correlates with cancer cell senescence and death, but how REV-ERBα play roles in tumor progression require further elucidation.MethodsWe investigated the expression of REV-ERBα in clinical samples by immunohistochemistry (IHC). REV-ERBα is downregulated by shorth hairpin RNA (shRNA). The gene expression level of each group was detected by Western blot analysis. The effects of REV-ERBα downregulation on apoptosis and cell cycles was assessed by flow cytometry assay. A549 cell growth curve under different treatments measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Cell invasion ability under different treatments was measured by Transwell assay. Immunostaining analysis was also used for evaluating the effects of downregulation of REV-ERBα on nuclear factor-κB (NF-κB).ResultsCompared to 81.8% (54/66) of samples exhibiting a lower expression level of REV-ERBα in cancer tissue than in paired normal tissue, only 18.2% (12/66) were higher or equally expressed in lung cancer tissue. Furthermore, downregulation of REV-ERBα by RNA interference can significantly enhance the transcription of nuclear factor-κB (NF-κB), while the expression of p53 remained the same. Downregulation of REV-ERBα was also shown to stimulate the invasion and promote the proliferation of lung adenocarcinoma cell line A549.ConclusionsOur findings suggest that tumorigenesis and progression of lung carcinoma is relevant to downregulation or inhibition of REV-ERBα. This pathophysiological process also correlates with regulation of the NF-κB signaling pathway, indicating that REV-ERBα is a potential target of lung cancer therapy.

Dataset Information

SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression.

Publications

SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression.

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