GPD1 represses colon cancer cell HCT-8 growth and indicates a favorable prognosis in colorectal cancer

doi:10.3969/j.issn.1006-7795.2019.04.027

Abstract

Abstract: Objective To explore the role of glycerol-3-phosphate dehydrogenase 1 (GPD1) in the development of colorectal cancer and its relationship with clinical prognosis. Methods HCT-8 colon cancer cell line was used in this study. Cell function experiments were performed after GPD1 expression knockdown by using siRNA. Cell proliferation activity and colony formation ability were detected by MTS assay and colony formation assay respectively. The migration ability was determined applying wound scratch assay and transwell assay. The bioinformatics analysis of the TCGA database explored the relationship between the expression level of GPD1 and the clinical prognosis of colorectal cancer patients. The relationship between the low expression of GPD1 in colorectal cancer and the methylation level of its coding gene was also explored. Results After interference of GPD1 gene expression by siRNA, the proliferation ability of HCT-8 cells was significantly enhanced (P<0.01). The results of colony formation experiments showed that the colony number and size of HCT-8 cell colonies significantly increased after GPD1 siRNA treatment (P<0.01). The results of the wound scratch test and transwell assay showed that there was no significant change in the migration ability of GPD1 knockdown HCT-8 cells, indicating that GPD1 had no effect on the migration ability of colon cancer cells. Bioinformatics analysis showed that the overall survival (χ²=4.1, P=0.040) and disease-free survival (χ²=13.2, P<0.000 1) of patients with low expression of GPD1 were significantly lower than those with high expression of GPD1. Also, low expression level of GPD1 was identified as an independent risk factor for poor prognosis of colorectal cancer (P<0.05). Methylation analysis showed that the low expression of GPD1 in colorectal cancer tissues was negatively correlated with hypermethylation of its coding gene (P<0.05). Conclusion GPD1 plays a role in inhibiting cell proliferation and colony formation in colon cancer, and low expression of GPD1 is an independent predictor of poor prognosis in patients with colorectal cancer.

Key words: colon cancer, GPD1, cell proliferation, prognosis

CLC Number:

R735.3⁺5

Min Li, Li Hengcun, Guo Qingdong, Wang Xingyu, Zhang Shutian. GPD1 represses colon cancer cell HCT-8 growth and indicates a favorable prognosis in colorectal cancer[J]. Journal of Capital Medical University, 2019, 40(4): 646-651.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2019.04.027

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2019/V40/I4/646

References 18

[1]	Torre L A, Bray F, Siegel R L, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015,65(2):87-108.
[2]	Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016,66(2):115-132.
[3]	Sadanandam A, Lyssiotis C A, Homicsko K, et al. A colorectal cancer classification system that associates cellular phenotype and responses to therapy[J]. Nat Med, 2013,19(5):619-625.
[4]	De Sousa E M F, Wang X, Jansen M, et al. Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions[J]. Nat Med, 2013,19(5):614-618.
[5]	Wu J W, Yang H, Wang S P, et al. Inborn errors of cytoplasmic triglyceride metabolism[J]. J Inherit Metab Dis, 2015,38(1):85-98.
[6]	Swierczynski J, Zabrocka L, Goyke E, et al. Enhanced glycerol 3-phosphate dehydrogenase activity in adipose tissue of obese humans[J]. Mol Cell Biochem, 2003,254(1-2):55-59.
[7]	Joshi M, Eagan J, Desai N K, et al. A compound heterozygous mutation in GPD1 causes hepatomegaly, steatohepatitis, and hypertriglyceridemia[J]. Eur J Hum Genet, 2014,22(10):1229-1232.
[8]	Basel-Vanagaite L, Zevit N, Har Zahav A, et al. Transient infantile hypertriglyceridemia, fatty liver, and hepatic fibrosis caused by mutated GPD1, encoding glycerol-3-phosphate dehydrogenase 1[J]. Am J Hum Genet, 2012,90(1):49-60.
[9]	Zhou C, Yu J, Wang M, et al. Identification of glycerol-3-phosphate dehydrogenase 1 as a tumour suppressor in human breast cancer[J]. Oncotarget, 2017,8(60):101309-101324.
[10]	Menaya J, Gonzalez-Manchon C, Parrilla R, et al. Molecular cloning, sequencing and expression of a cDNA encoding a human liver NAD-dependent alpha-glycerol-3-phosphate dehydrogenase[J]. Biochim Biophys Acta, 1995,1262(1):91-94.
[11]	Bestor T H, Edwards J R, Boulard M. Notes on the role of dynamic DNA methylation in mammalian development[J]. Proc Natl Acad Sci U S A, 2015,112(22):6796-6799.
[12]	Descotes F, Jezequel P, Spyratos F, et al. Identification of potential prognostic biomarkers for node-negative breast tumours by proteomic analysis:a multicentric 2004 national PHRC study[J]. Int J Oncol, 2012,41(1):92-104.
[13]	Hanahan D, Weinberg R A. Hallmarks of cancer:the next generation[J]. Cell, 2011,144(5):646-674.
[14]	Warburg O, Wind F, Negelein E. The metabolism of tumors in the body[J]. J Gen Physiol, 1927,8(6):519-530.
[15]	Vander Heiden M G, Cantley L C, Thompson C B. Understanding the Warburg effect:the metabolic requirements of cell proliferation[J]. Science, 2009,324(5930):1029-1033.
[16]	Hsu P P, Sabatini D M. Cancer cell metabolism:warburg and beyond[J]. Cell, 2008,134(5):703-707.
[17]	李晶, 黄三钱, 欧阳取长, 等. 三阴性与三阳性乳腺癌定量蛋白质组学和生物信息学比较研究[J]. 中华肿瘤防治杂志, 2016, 23(16):1053-1059.
[18]	Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas[J]. Gastroenterology, 2007,132(6):2208-2225.