- Volume 15 Issue 21
DOI QR Code
Structural Maintenance of Chromosomes 4 is a Predictor of Survival and a Novel Therapeutic Target in Colorectal Cancer
- Feng, Xiao-Dong (Department of Basic Medicine, Taishan Medical University) ;
- Song, Qi (Department of Basic Medicine, Taishan Medical University) ;
- Li, Chuan-Wei (Department of Basic Medicine, Taishan Medical University) ;
- Chen, Jian (Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital) ;
- Tang, Hua-Mei (Department of Pathology, Shanghai Jiaotong University Affiliated First People's Hospital) ;
- Peng, Zhi-Hai (Department of General Surgery, Shanghai Jiaotong University Affiliated First People's Hospital) ;
- Wang, Xue-Chun (Department of Basic Medicine, Taishan Medical University)
- Published : 2014.11.28
Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.
- Bidkhori G, Narimani Z, Hosseini Ashtiani S, et al (2013). Reconstruction of an integrated genome-scale co-expression network reveals key modules involved in lung adenocarcinoma. PLoS One, 8.
- Chang A (2011). Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer, 71, 3-10. https://doi.org/10.1016/j.lungcan.2010.08.022
- Chen Q, Xia HW, Ge XJ, et al (2013). Serum miR-19a predicts resistance to FOLFOX chemotherapy in advanced colorectal cancer cases. Asian Pac J Cancer Prev, 14, 7421-6. https://doi.org/10.7314/APJCP.2013.14.12.7421
- Goel A, Boland CR (2010). Recent insights into the pathogenesis of colorectal cancer. Curr Opin Gastroenterol, 26, 47-52. https://doi.org/10.1097/MOG.0b013e328332b850
- Griese JJ, Witte G, Hopfner KP (2010). Structure and DNA binding activity of the mouse condensin hinge domain highlight common and diverse features of SMC proteins. Nucleic Acids Res, 38, 3454-65. https://doi.org/10.1093/nar/gkq038
- Hagstrom KA, Holmes VF, Cozzarelli NR, et al (2002). C. elegans condensin promotes mitotic chromosome architecture, centromere organization, and sister chromatid segregation during mitosis and meiosis. Genes Dev, 16, 729-42. https://doi.org/10.1101/gad.968302
- Harvey SH, Krien MJ, O'Connell MJ (2002). Structural maintenance of chromosomes (SMC) proteins, a family of conserved ATPases. Genome Biol, 3, 30.
- Hui AB, Takano H, Lo KW, et al (2005). Identification of a novel homozygous deletion region at 6q23.1 in medulloblastomas using high-resolution array comparative genomic hybridization analysis. Clin Cancer Res, 11, 4707-16. https://doi.org/10.1158/1078-0432.CCR-05-0128
- Jinushi T, Shibayama Y, Kinoshita I, et al (2014). Low expression levels of microRNA-124-5p correlated with poor prognosis in colorectal cancer via targeting of SMC4. Cancer Med, 1, 309.
- Kawachi H, Sugahara K, Nakamura Y, et al (2013). Deletion polymorphism at chromosome 3q26.1 and oral squamous cell carcinoma. Int J Oncol, 42, 384-90.
- Kulawiec M, Safina A, Desouki MM, et al (2008). Tumorigenic transformation of human breast epithelial cells induced by mitochondrial DNA depletion. Cancer Biol Ther, 7, 1732-43. https://doi.org/10.4161/cbt.7.11.6729
- Losada A, Hirano T (2005). Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev, 19, 1269-87. https://doi.org/10.1101/gad.1320505
- Lu KH, Patterson AP, Wang L, et al (2004). Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res, 10, 3291-300. https://doi.org/10.1158/1078-0432.CCR-03-0409
- Nishiwaki T, Daigo Y, Kawasoe T, et al (1999). Isolation and characterization of a human cDNA homologous to the Xenopus laevis XCAP-C gene belonging to the structural maintenance of chromosomes (SMC) family. J Hum Genet, 44, 197-202. https://doi.org/10.1007/s100380050142
- Ono T, Losada A, Hirano M, et al (2003). Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell, 115, 109-21. https://doi.org/10.1016/S0092-8674(03)00724-4
- Petrova TV, Nykanen A, Norrmen C, et al (2008). Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. Cancer Cell, 13, 407-19. https://doi.org/10.1016/j.ccr.2008.02.020
- Sansom OJ, Meniel VS, Muncan V, et al (2007). Myc deletion rescues Apc deficiency in the small intestine. Nature, 446, 676-9. https://doi.org/10.1038/nature05674
- Siegel R, Desantis C, Jemal A (2014). Colorectal cancer statistics, 2014. CA Cancer J Clin, 64, 104-17. https://doi.org/10.3322/caac.21220
- Takahashi S, Fusaki N, Ohta S, et al (2012). Downregulation of KIF23 suppresses glioma proliferation. J Neurooncol, 106, 519-29. https://doi.org/10.1007/s11060-011-0706-2
- Thean LF, Loi C, Ho KS, et al (2010). Genome-wide scan identifies a copy number variable region at 3q26 that regulates PPM1L in APC mutation-negative familial colorectal cancer patients. Genes Chromosomes Cancer, 49, 99-106.
- Wang Y, Klijn JG, Zhang Y, et al (2005). Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet, 365, 671-9. https://doi.org/10.1016/S0140-6736(05)70933-8
- Wirtenberger M, Frank B, Hemminki K, et al (2006). Interaction of Werner and Bloom syndrome genes with p53 in familial breast cancer. Carcinogenesis, 27, 1655-60.
- Yan DW, Li DW, Yang YX, et al (2010). Ubiquitin D is correlated with colon cancer progression and predicts recurrence for stage II-III disease after curative surgery. Br J Cancer, 103, 961-9. https://doi.org/10.1038/sj.bjc.6605870
- Zhai L, Wang H, Tang W, et al (2011). Disturbance in function and expression of condensin affects chromosome compaction in HeLa cells. Cell Biol Int, 35, 735-40. https://doi.org/10.1042/CBI20100646
- Zhou B, Yuan T, Liu M, et al (2012). Overexpression of the structural maintenance of chromosome 4 protein is associated with tumor de-differentiation, advanced stage and vascular invasion of primary liver cancer. Oncol Rep, 28, 1263-8.
- Zhu JH, Hong DF, Song YM, et al (2013). Suppression of cellular apoptosis susceptibility (CSE1L) inhibits proliferation and induces apoptosis in colorectal cancer cells. Asian Pac J Cancer Prev, 14, 1017-21. https://doi.org/10.7314/APJCP.2013.14.2.1017
- Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition vol.12, pp.11, 2017, https://doi.org/10.1371/journal.pone.0188739
- Overexpression of SMC4 activates TGFβ/Smad signaling and promotes aggressive phenotype in glioma cells vol.6, pp.3, 2017, https://doi.org/10.1038/oncsis.2017.8
- induced acute myeloid leukemia pp.1029-2403, 2017, https://doi.org/10.1080/10428194.2017.1387906
- DNA Repair—A Double-Edged Sword in the Genomic Stability of Cancer Cells—The Case of Chronic Myeloid Leukemia vol.16, pp.11, 2015, https://doi.org/10.3390/ijms161126049
- Subunits of human condensins are potential therapeutic targets for cancers vol.13, pp.1, 2018, https://doi.org/10.1186/s13008-018-0035-3
- Silencing non-SMC chromosome-associated polypeptide G inhibits proliferation and induces apoptosis in hepatocellular carcinoma cells pp.1205-7541, 2018, https://doi.org/10.1139/cjpp-2018-0195