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.
Highlights
Conserved hinge motif on the central domain[15,16,17]
Because tumorigenesis is considered the reverse process of embryonic development, genes that are downregulate during lung development (PTN1 and PTN2) may be upregulated in lung cancer, whereas genes that are upregulated during lung development (PTN25 and PTN27) may be downregulated in lung cancer
The statistical analysis suggested the inclusion of 1640 genes in the four PTNs; of these, 613 genes showed opposite expression patterns in lung ADCs, 31 genes were continuously upregulated or downregulated in lung ADCs, and the remaining 996 genes demonstrated no significant changes in lung ADCs compared with adult lung tissues (AduL) collected from adult patients who had undergone surgery for benign lung diseases (Fig. 1A)
Summary
Conserved hinge motif on the central domain[15,16,17]. The most widely reported function of SMC4, as well as the remaining subunits of whole condensin complexes, is chromosome condensation and segregation. The role of SMC4 in lung ADC carcinogenesis has not yet been reported. We identified SMC4 through the construction of a co-expression network of genes that exhibit constant changes in expression during lung development. The microarray data analysis and cell experiments revealed that SMC4 is closely related to the tumor cell cycle, cell adhesion, and RNA processing. These results suggests that SMC4 has important functions in both lung development and lung cancer progression. The findings of this study demonstrate that the investigation of cancer through a comparative study between development and tumorigenesis will allow an easier identification of potential therapeutic targets and biomarkers and a more in-depth understanding of the mechanisms of carcinogenesis
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