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《5-雜氮-2’脫氧胞苷對(duì)肝癌細(xì)胞中timp-3基因的作用》由會(huì)員上傳分享，免費(fèi)在線(xiàn)閱讀，更多相關(guān)內(nèi)容在學(xué)術(shù)論文-天天文庫(kù)。
1、一340一現(xiàn)代消化及介入診療2013年第18卷第6期ModemDigestion＆Intervention2013，Vo!No·6·論著·5一雜氮一2脫氧胞苷對(duì)肝癌細(xì)胞中TIMP一3基因的作用曾偉沈波聶玉強(qiáng)李?lèi)?ài)民陳阮然【摘要】目的觀察多株肝癌細(xì)胞中TIMP一3CpG島的甲基化狀況，觀察甲基化藥物5一雜氮一2脫氧胞苷對(duì)肝癌細(xì)胞株中TIMP一3基因表達(dá)及其CpG島甲基化程度的影響。方法運(yùn)用MSP定性檢測(cè)8株肝癌細(xì)胞中TIMP一3CpG島甲基化狀況。使用去甲基化藥物5一雜氮一2脫氧胞苷對(duì)甲基化陽(yáng)性的細(xì)胞株進(jìn)行干預(yù)
2、，觀察干預(yù)組與對(duì)照組TIMP-3基因表達(dá)差異，并使用焦磷酸測(cè)序技術(shù)定量檢測(cè)CpG島甲基化差異。結(jié)果在8株肝癌細(xì)胞系中C3A、Hep一3B、HepG23株檢測(cè)到TIMP一3CpG島甲基化陽(yáng)性。經(jīng)去甲基化藥物干預(yù)后，在這3株肝癌細(xì)胞中均發(fā)現(xiàn)TIMP一3mRNA的表達(dá)較對(duì)照組有明顯上調(diào)(P<0．05)，CpG島的甲基化率下降(P<0．05)。結(jié)論甲基轉(zhuǎn)移酶抑制劑能顯著降低肝癌細(xì)胞株TIMP一3CpG島甲基化程度及上調(diào)TIMP一3mRNA的表達(dá)。【關(guān)鍵詞】肝癌；TIMP一3；甲基化；5一雜氮一2脫氧胞苷Theefe
3、ctof5．．Aza—-CdRonTIMP——3geneinhepatocellularcarcinomaceHsZENGWei,SHENBo．NIEYu-qiang．LlAi—min，CHENRuan—ran．GuangzhouKeyLaboratoryofDigestiveDisease，DepartmentofGastroenterology，F(xiàn)irstMunicipalPeoplesHospitalofGuangzhou，GuangzhouMedicalUniversity，Guangzhou510
4、180,China【Abstract】ObjeetiveTheaimofthisstudyistoinvestigatetheCpGislandmethylationstatusofTIMP一3inHCCcelllines．totreatetheHCCcellsthatexhibitpositivemethylationwithDNAmethyltransferasein—hibitor(5-Aza-CdR)，andtoobservetheinfluenceof5一Aza—CdRontheexpressio
5、nofTIMP一3mRNAanditsCpGislandmethylationdegree．MethodsTIMP-3CpGmethylationstatusofHCCcellswereexaminedusingMSPassay．Methylation—positiveHCCcellsweretreatedwithDNAmethyltransferaseinhibitor(5-Aza—CdR)(interventiongroup)，andthedifferenceofTIMP-3mRNAexpression
6、wasobservedbetweeninterven—tiongroupandcontrolgroup．PyrosequencingmethodwasappliedtoquantitativelyexaminetheCpGislandmethylationpercentage．ResultsThemethylationofTIMP一3CpGislandsinC3A，HepG一2，andHep一3Bwaspositive．TheresultsshowedthatTIMP-3mRNAexpressionwasi
7、ncreased(尸<0．05)andthemethylationlevelwasdecreased(P<0．05)intheinterventiongroupcomparedtocontrolgroup．Conclusion5-Aza—CdRcouldremarkablyreducetheleveloftheCpGislandmethylationandincreasetheexpressionofTIMP-3mR—NAinHCCcells．【Keywords】HCC；TIMP-3；Methylation
8、；5-Aza一2'-deoxycytidineDNA的甲基化屬于表觀遺傳學(xué)范疇．它對(duì)基因從而生成甲基化DNA。人類(lèi)中DNA甲基化大多發(fā)表達(dá)的調(diào)控不依賴(lài)于基因序列改變，DNA甲基轉(zhuǎn)移生于CpG二核苷酸的胞嘧啶上DNA甲基化通常通酶(DNAmethyltransferase，DNMTs)將甲基集團(tuán)催過(guò)抑制轉(zhuǎn)錄因子與啟動(dòng)子結(jié)合【1J，改變?nèi)旧|(zhì)結(jié)構(gòu)，化，轉(zhuǎn)移到5'-CpG一3中胞嘧啶的第五位碳原子上。促進(jìn)轉(zhuǎn)錄抑制子的結(jié)
