干扰SIRT7抑制甲状腺癌细胞的增殖、迁移和侵袭能力
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摘要
目的:研究干扰SIRT7对甲状腺癌细胞BCPAP的体外增殖、迁移和侵袭能力的影响。方法:通过慢病毒构建干扰SIRT7的甲状腺癌BCPAP的稳定株,并在mRNA和蛋白水平验证干扰效果,然后通过CCK-8、细胞划痕、细胞迁移和细胞侵袭实验来研究SIRT7对甲状腺癌细胞BCPAP体外增殖、迁移和侵袭能力的影响。结果:成功构建干扰SIRT7的甲状腺癌细胞BCPAP的稳定株;干扰SIRT7之后,甲状腺癌细胞BCPAP的体外增殖活力显著降低,划痕愈合能力、细胞迁移和侵袭能力也明显减弱,差异均有统计学意义(P<0.05)。结论:SIRT7可能在甲状腺癌中扮演了癌基因的角色,并且SIRT7可能是甲状腺癌一个潜在的治疗靶点。
Objective: To study the effect of interfering SIRT7 on the proliferation, migration and invasion of thyroid cancer cell BCPAP in vitro. Methods: The stable strain of BCPAP interferred with SIRT7 was constructed by lentivirus, and the interference effect was verified at mRNA and protein levels. The effects of SIRT7 on the proliferation, migration and invasion of thyroid cancer BCPAP in vitro were studied by cell migration and cell invasion assay. Results: The stable cell line of BCPAP interfered with SIRT7 was successfully constructed, and after interfering SIRT7, the proliferation activity of BCPAP, the ability of scar healing and the ability of cell migration and invasion were significantly decrease and showed statistical difference(P<0.05). Conclusion:SIRT7 might play a role as an oncogene in thyroid cancer and could be considered a potential therapeutic target against thyroid cancer.
Objective: To study the effect of interfering SIRT7 on the proliferation, migration and invasion of thyroid cancer cell BCPAP in vitro. Methods: The stable strain of BCPAP interferred with SIRT7 was constructed by lentivirus, and the interference effect was verified at mRNA and protein levels. The effects of SIRT7 on the proliferation, migration and invasion of thyroid cancer BCPAP in vitro were studied by cell migration and cell invasion assay. Results: The stable cell line of BCPAP interfered with SIRT7 was successfully constructed, and after interfering SIRT7, the proliferation activity of BCPAP, the ability of scar healing and the ability of cell migration and invasion were significantly decrease and showed statistical difference(P<0.05). Conclusion:SIRT7 might play a role as an oncogene in thyroid cancer and could be considered a potential therapeutic target against thyroid cancer.
引文
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[4]VAKHRUSHEVA O,BRAEUER D,LIU Z,et al.Sirt7-dependent inhibition of cell growth and proliferation might be instrumental to mediate tissue integrity during aging[J].JPhysiol Pharmacol,2008,59 Suppl 9:201-212.
[5]BARBER M F,MICHISHITA-KIOI E,XI Y,et al.SIRT7links H3K18 deacetylation to maintenance of oncogenic transformation[J].Nature,2012,487(7405):114-118.
[6]DE NIGRIS F,CERUTTI J,MORELLI C,et al.Isolation of a SIR-like gene,SIR-T8,that is overexpressed in thyroid carcinoma cell lines and tissues[J].Br J Cancer,2002,87(12):1479.
[7]ALJADA A,SALEH A M,ALKATHIRI M,et al.Altered Sirtuin 7 expression is associated with early stage breast cancer[J].Breast Cancer(Auckl),2015,9:3-8.
[8]CHEN Z,CHEN X,HAN W,et al.The expression of SIRT7was down-regulated and correlated with tumor size in thyroid carcinoma[J].Int J Clin Exp Med,2016,9(5):8320-8326.
[9]丁婷婷,吴杭菲,刘成,等.SIRT1在非酒精性脂肪肝病大鼠肝脏中的表达及姜黄素衍生物L6H4的干预作用[J].温州医科大学学报,2018,48(4):235-240.
[10]ROTH M,CHEN W Y.Sorting out functions of sirtuins in cancer[J].Oncogene,2014,33(13):1609-1620.
[11]CHA E J,NOH S J,KWON K S,et al.Expression of DBC1and SIRT1 is associated with poor prognosis of gastric carcinoma[J].Clin Cancer Res,2009,15(13):4453-4459.
[12]STüNKEL W,PEH B K,TAN Y C,et al.Function of the SIRT1 protein deacetylase in cancer[J].Biotechnol J,2007,2(11):1360-1368.
[13]HUFFMAN D M,GRIZZLE W E,BAMMAN M M,et al.SIRT1 is significantly elevated in mouse and human prostate cancer[J].Cancer Res,2007,67(14):6612-6618.
[14]HIDA Y,KUBO Y,MURAO K,et al.Strong expression of a longevity-related protein,SIRT1,in Bowen's disease[J].Arch Dermatol Res,2007,299(2):103-106.
[15]WANG R H,SENGUPTA K,LI C,et al.Impaired DNAdamage response,genome instability,and tumorigenesis in SIRT1 mutant mice[J].Cancer Cell,2008,14(4):312-323.
[16]FIRESTEIN R,BLANDER G,MICHAN S,et al.The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth[J].PLoS One,2008,3(4):e2020.
[17]KIM H S,VASSILOPOULOS A,WANG R H,et al.SIRT2maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity[J].Cancer Cell,2011,20(4):487-499.
[18]HIRATSUKA M,INOUE T,TODA T,et al.Proteomicsbased identification of differentially expressed genes in human gliomas:down-regulation of SIRT2 gene[J].Biochem Biophys Res Commun,2003,309(3):558-566.
[19]MING M,QIANG L,ZHAO B,et al.Mammalian SIRT2inhibits keratin 19 expression and is a tumor suppressor in skin[J].Exp Dermatol,2014,23(3):207-209.
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[22]KIM J K,NOH J H,JUNG K H,et al.Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b[J].Hepatology,2013,57(3):1055-1067.
[23]YU H,YE W,WU J,et al.Overexpression of sirt7 exhibits oncogenic property and serves as a prognostic factor in colorectal cancer[J].Clin Cancer Res,2014,20(13):3434-3445.
[24]ASHRAF N,ZINO S,MACINTYRE A,et al.Altered sirtuin expression is associated with node-positive breast cancer[J].Br J Cancer,2006,95(8):1056-1061.
[25]GENG Q,PENG H,CHEN F,et al.High expression of Sirt7served as a predictor of adverse outcome in breast cancer[J].Int J Clin Exp Pathol,2015,8(2):1938-1945.
[26]ZHANG S,CHEN P,HUANG Z,et al.Sirt7 promotes gastric cancer growth and inhibits apoptosis by epigenetically inhibiting miR-34a[J].Sci Rep,2015,5:9787.
[27]WANG H L,LU R Q,XIE S H,et al.SIRT7 exhibits oncogenic potential in human ovarian cancer cells[J].Asian Pac JCancer Prev,2015,16(8):3573-3577.
[28]MCGLYNN L M,MCCLUNEY S,JAMIESON N B,et al.SIRT3&SIRT7:Potential novel biomarkers for determining outcome in pancreatic cancer patients[J].PLoS One,2015,10(6):e0131344.