探討 ZFP36L1 在人類結腸直腸癌細胞生長之角色

The study of the role of ZFP36L1 in humer colorectal cancer cell groth

楊寶琳(Pao-Lin Yang)

指導教授 ： 梁有志

臺北醫學大學/醫學科技學院/醫學檢驗暨生物技術學系/碩士(2013年)

https://doi.org/10.6831/TMU.2013.00147

摘要

ZFP36家族被研究出和RNA代謝相關，包括mRNA剪接、mRNA運送、以及mRNA之穩定性和分解。調控mRNA之機制非常嚴謹，並且為調控基因表達之關鍵。許多疾病中mRNA調控失常，導致許多生長因子、發炎相關之細胞激素或是至癌基因大量表現。
然而ZFP36L1鋅指蛋白在大腸直腸癌中扮演的角色的瞭解是相當有限的，本實驗收集臨床大腸直腸癌的組織研究探討ZFP36L1和大腸直腸癌的相關性。初步結果發現有ZFP36L1基因在大腸直腸癌之表現量比正常組織中高。並進一步探討ZFP36L1對於結腸直腸癌細胞之影響，利用慢病毒(lentivirus)建立ZFP36L1 knockdown stable cell line以及過度表現ZFP36L1之結腸直腸癌細胞，於SW62細胞抑制ZFP36L1的與HCT116細胞過度表現ZFP36L1會減少結腸直腸癌細胞增生，並使其Cyclin、p-histone H3、p-AKT與p-ERK1/2蛋白表現量降低;高度表現ZFP36L1於HT29細胞與HCT116 p53-/-細胞會增加結腸直腸癌細胞增生，其Cyclin、p-histone H3、p-AKT與p-ERK1/2蛋白表現量上升。並且於HCT116細胞中過度表現ZFP36L1可使wild type p53大量表現。由此得知，ZFP36L1可能在結腸直腸癌中扮演促進細胞增生的角色並與p53之間有關係。

關鍵字

ZFP36L1 ； p53

並列摘要

ZFP36 family has been reported involved in RNA metabolisms including pre-mRNA splicing, mRNA transportation, subcellular localization, and stability/degradation. mRNA turnover is a tightly regulated process that is critical in controlling mammalian gene expression. The importance of this level of regulation is evident in a variety of diseases which loss of posttranscriptional gene regulation directly contributes to the overexpression of many genes encoding growth factors, inflammatory cytokines, and proto-oncogenes.
However, the role of ZFP36L1 in colorectal cancer still doesn’t clearly understand. In this study, we collect colorectal cancer tissues to investigate the relationship between ZFP36L1 and colorectal cancer. Our recent studies have shown ZFP36L1 genes expression in the colon cancer tissue was increased. To investigate functions of ZFP36L1 in colorectal cancer cells, we knockdowned or overexpressed ZFP36L1 gene by lentvirus-mediated gene delivery system. We found knockdown of ZFP36L1 in SW620 cells and overexpression of ZFP36L1 in HCT116 cells decreased cell viability and colony formation. Besides, the expression of Cyclin, p-histone H3, p-AKT and p-ERK1/2 were decreased. Overexpression of ZFP36L1 increased HT29 cells and HCT116 p53-/- cells viability and colony formation. The expression of Cyclin, p-histone H3, p-AKT and p-ERK1/2 were increased. Moreover, the protein level of p53 in HCT116 cells which overexpressed ZFP36L1were increased. In conclusion, results from this study suggest that ZFP36L1 can promote cell proliferation in colorectal cancer cell and have relationship with p53.

並列關鍵字

ZFP36L1 ； p53

參考文獻

66. Zhu, L.B.a.W.-G., p53: Structure, Function and Therapeutic Applications. Journal of Cancer Molecules, 2006. 2(4): p. 141-153.

1. McConnell, E.L., F. Liu, and A.W. Basit, Colonic treatments and targets: issues and opportunities. J Drug Target, 2009. 17(5): p. 335-63.

2. Siegel, R., D. Naishadham, and A. Jemal, Cancer statistics, 2012. CA Cancer J Clin, 2012. 62(1): p. 10-29.

3. Haggar, F.A. and R.P. Boushey, Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg, 2009. 22(4): p. 191-7.

4. Yee, Y.K., et al., Epidemiology of colorectal cancer in Asia. J Gastroenterol Hepatol, 2009. 24(12): p. 1810-6.