宫颈癌组织APOBEC3A蛋白的表达与高危型HPV感染的相关性研究

Correlation of human APOBEC3A protein expression with high-risk HPV infection in cervical cancer tissues

目的:探讨宫颈癌组织中载脂蛋白B mRNA编辑酶催化多肽样蛋白3A(APOBEC3A)表达与高危型人乳头瘤病毒(HPV)感染的关系。方法:采用免疫组化法检测26例宫颈癌、27例宫颈上皮内瘤变(CIN)I～III和22例正常宫颈组织APOBEC3A蛋白的表达,同时使用凯普分型检测试剂盒对3组样品分别进行高危HPV16/HPV18分型检测。以脂质体法转染APOBEC3A质粒进入HeLa细胞,RT-qPCR与Western blotting验证APOBEC3A对高危型HPV18 E6 mRNA以及蛋白表达的影响。结果:宫颈癌组织、CIN组织以及正常宫颈组织中APOBEC3A蛋白表达的阳性率分别为46.2%、92.6%和86.4%,宫颈癌组织中APOBEC3A蛋白表达较正常宫颈组织明显下降(P<0.01)。宫颈癌组织、CIN及正常宫颈组织中HPV16感染阳性率分别为92.3%、77.8%和54.5%;HPV18感染阳性率分别为80.8%、51.8%和68.2%;APOBEC3A蛋白表达与HPV18感染阳性率呈负相关(P<0.05)。增加HeLa细胞中APOBEC3A的表达明显降低了HPV18 E6 mRNA以及蛋白的表达。结论:在宫颈癌组织中APOBEC3A高表达可以对抗HPV18感染,并抑制HPV18 E6的转录和表达。

AIM： To study the effects of human apolipoprotein B mRNA-editing catalytic polypeptide-like pro- tein 3A （APOBEC3A） on high-risk human papiUomavirus （HPV） in cervical cancer tissues. METHODS： Immunohisto- chemistry technique was used to detect the expression of human APOBEC3A protein, and Hybribio HPV GenoArray diag- nostic kit was used to measure high-risk HPV16 and HPV18 in the specimens from 26 cases of cervical cancer, 27 cases of cervical intraepithelial neoplasia （CIN） I ~III and 22 cases of normal cervix. The APOBEC3A plasmid was transfected into HeLa cells by Lipofectamine. The expression of HPV18 E6 at mRNA and protein levels was examined by RT-qPCR and Western blotting. RESULTS： The protein expression of APOBEC3A in cervical cancer, CIN and normal cervix was 46. 2%, 92.6% and 86.4%, respectively. The protein expression of APOBEC3A in cervical cancer was significantly de- creased compared with that in normal cervix （P 〈0. 01 ）. The infection rates of HPV16 in cervical cancer, CIN and normal cervix were 92.3%, 77.8% and 54.5%, respectively, and those of HPV18 were 80.8%, 51.8%, 68.2%, respective- ly. The protein expression of APOBEC3A was negatively correlated with the infection of HPV18 in cervical tissues （P 〈 0. 05）. Compared with control group, the expression of HPV18 E6 at mRNA and protein levels was decreased after APO- BEC3A plasmid was transfected into HeLa cells. CONCLUSION： In cervical cancer, the high expression of APOBEC3A protein may fight against HPV18 infection, and APOBEC3A inhibits HPV18 E6 transcription and expression.