hnRNP E1与HPV16及其早期蛋白E2在宫颈上皮内瘤样变中的相互关系研究
|
摘要
目的探讨hnRNP E1与HPV16及其早期蛋白E2在宫颈上皮内瘤样变(CIN)中的交互作用。方法问卷收集研究对象CIN相关因素,采集宫颈组织和宫颈脱落细胞。分子导流杂交技术检测HPV16感染状况,western blot法检测hnRNP E1及HPV16 E2蛋白量。结果 HPV16阳性率随宫颈病变程度加重,呈现上升趋势(P<0.001),CINⅡ/Ⅲ组E2蛋白表达量低于CINⅠ和NC组(P<0.05),且随宫颈病变程度进展,其低表达率呈现升高的趋势。CINⅡ/Ⅲ组的hnRNP E1蛋白表达量低于NC组(P<0.001)。hnRNP E1蛋白与HPV16 E2蛋白间存在正相关关系。hnRNP E1蛋白低表达与HPV16感染在CINⅡ/Ⅲ发生中呈正相加交互作用,但在CINⅠ组未发现类似交互作用。结论 hnRNP E1蛋白低表达与HPV16感染、HPV16 E2蛋白低表达均可增加CIN的患病风险,HPV16感染与hnRNP E1蛋白在高级别CIN患病中可能存在协同作用。
Objective To investigate the interaction between heterogeneous nuclear ribonucleoprotein E1(hnRNP E1) and HPV16 and its early protein E2 in cervical intraepithelial neoplasia. Methods A structured questionnaire was used to collect related factors of CIN. Cervical tissue and exfoliated cells were collected. The infection status of HPV16 was detected by hybridization technique. The protein expression levels of hnRNP E1 and HPV16 E2 were detected by Western blot. Results HPV16 positive rate increased along with the severity of cervical lesions(P<0.001). HPV16 E2 protein expression levels in CIN II/III group were lower than that in CIN I and NC group(P <0.05). The low expression rate of E2 protein showed an increasing trend along with the severity of cervical lesions. The protein expression levels of hnRNP E1 in CIN II/III group were significantly lower than those in NC group(P<0.001). There was a positive correlation between hnRNP E1 and HPV16 E2. There was positive additive interaction between low expression of hnRNP E1 and HPV16 infection in CIN II/III group.However, we did not find the same rule in CIN I group. Conclusion HPV16 infection, low protein expression of HPV16 E2 and hnRNP E1 were associated with the increased risk of CIN. There might be interaction between hnRNP E1 low protein expression and HPV16 infection on the progress of CIN Ⅱ/Ⅲ.
Objective To investigate the interaction between heterogeneous nuclear ribonucleoprotein E1(hnRNP E1) and HPV16 and its early protein E2 in cervical intraepithelial neoplasia. Methods A structured questionnaire was used to collect related factors of CIN. Cervical tissue and exfoliated cells were collected. The infection status of HPV16 was detected by hybridization technique. The protein expression levels of hnRNP E1 and HPV16 E2 were detected by Western blot. Results HPV16 positive rate increased along with the severity of cervical lesions(P<0.001). HPV16 E2 protein expression levels in CIN II/III group were lower than that in CIN I and NC group(P <0.05). The low expression rate of E2 protein showed an increasing trend along with the severity of cervical lesions. The protein expression levels of hnRNP E1 in CIN II/III group were significantly lower than those in NC group(P<0.001). There was a positive correlation between hnRNP E1 and HPV16 E2. There was positive additive interaction between low expression of hnRNP E1 and HPV16 infection in CIN II/III group.However, we did not find the same rule in CIN I group. Conclusion HPV16 infection, low protein expression of HPV16 E2 and hnRNP E1 were associated with the increased risk of CIN. There might be interaction between hnRNP E1 low protein expression and HPV16 infection on the progress of CIN Ⅱ/Ⅲ.
引文
[1]Ferlay J,Soerjomataram I,Dikshit R,et al.Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J].International journal of cancer.Journal international du cancer,2015,136(5):E359-E386.
[2]Guan P,Howell-Jones R,Li N,et al.Human papillomavirus types in 115,789 HPV-positive women:A meta-analysis from cervical infection to cancer[J].International Journal of Cancer,2012,131(10):2349-2359.
[3]Graham SV.Human papillomavirus E2 protein:linking replication,transcription,and RNA processing[J].Journal of Virology,2016,90(19):8384-8388.
[4]王金桃,丁玲,高尔生,等.人乳头瘤病毒16 E2、E6癌基因在子宫颈癌中的表达及E2缺失分析[J].中华流行病学杂志,2007,28(10):968-971.
[5]Kajitani N,Schwartz S.RNA binding proteins that control human papillomavirus gene expression[J].Biomolecules,2015,5(2):758-774.
[6]Ghanem LR,Chatterji P,Liebhaber SA.Specific enrichment of the RNA-binding proteins PCBP1 and PCBP2 in chief cells of the murine gastric mucosa[J].Gene Expression Patterns,2014,14(2):78-87.
[7]Graham SV,Faizo AA.Control of human papillomavirus gene expression by alternative splicing[J].Virus Research,2017,231(SI):83-95.
[8]Wu CJ,Kajitani N,Schwartz S.Splicing and polyadenylation of human papillomavirus type 16 m RNAs[J].International Journal of Molecular Sciences,2017,18(2):E366.
[9]Pillai MR,Chacko P,Kesari L,et al.Expression of folate receptors and heterogeneous nuclear ribonucleoprotein E1 in women with human papillomavirus mediated transformation of cervical tissue to cancer[J].Journal of Clinical Pathology,2003,56(8):569-574.
[10]Pathak S,Bajpai D,Banerjee A,et al.Serum One-Carbon metabolites and risk of cervical cancer[J].Nutrition and Cancer-An International Journal,2014,66(5):818-824.
[11]Macdonald OK,Chen J,Dodson M,et al.Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix[J].American journal of clinical oncology,2009,32(4):411-416.
[12]王丽双,毛原夫,杨晶,等.CINⅠ、CINⅡ及CINⅢ发病高危因素的多因素Logistic回归分析[J].河北医科大学学报,2012,33(11):1315-1317.
[13]Collins S,Rollason TP,Young LS,et al.Cigarette smoking is an Independent risk factor for cervical intraepithelial neoplasia in young women:a longitudinal study[J].European journal of cancer(Oxford,England:1990),2010,46(2):405-411.
[14]Mclntyre-Seltman K,Castle PE,Guido R,et al.Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology[J].Cancer Epidemiology,Biomarkers&Prevention,2005,14(5):1165-1170.
[15]Chaudhury A,Chander P,Howe PH.Heterogeneous nuclear ribonucleoproteins(hnRNPs)in cellular processes:focus on hnRNP E1's multifunctional regulatory roles[J].RNA(New York,N.Y.),2010,16(8):1449-1462.
[16]Li J,Feng Q,Wei X,et al.Micro RNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1[J].Tumor Biology,2016,37(11):15221-15228.
[17]Zhang MP,Wang X,Tan J,et al.Poly r(C)binding protein(PCBP)1is a negative regulator of thyroid carcinoma[J].American journal of translational research,2016,8(8):3567-3573.
[18]Zhang MP,Zhang WS,Tan J,et al.Poly r(C)binding protein(PCBP)1 expression is regulated at the post-translation level in thyroid carcinoma[J].American journal of translational research,2017,9(2):708-714.
[19]Zeng Z,Yang H,Li Z,et al.Prevalence and genotype distribution of HPV infection in China:analysis of 51,345 HPV genotyping results from China's largest CAP certified laboratory[J].Journal of Cancer,2016,7(9):1037-1043.
[20]Kjaer SK,Munk C,Junge J,et al.Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology,ASCUS/LSIL,HSIL,or cervical cancer:what is the potential for prevention?[J].Cancer Causes&Control,2014,25(2):179-189.
[21]Egawa N,Egawa K,Griffin H,et al.Human papillomaviruses;epithelial tropisms,and the development of neoplasia[J].Viruses,2015,7(7):3863-3890.
[22]Vogt M,Butz K,Dymalla S,et al.Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein[J].Oncogene,2006,25(29):4009-4015.
[23]Collier B,Goobar-Larsson L,Sokolowski M,Schwartz S.Translational inhibition in vitro of human papillomavirus type 16 L2 m RNAmediated through interaction with heterogeneous ribonucleoprotein Kand poly(r C)-binding protein 1 and 2[J].Journal of Biological Chemistry,273(35):22648-22656.
[2]Guan P,Howell-Jones R,Li N,et al.Human papillomavirus types in 115,789 HPV-positive women:A meta-analysis from cervical infection to cancer[J].International Journal of Cancer,2012,131(10):2349-2359.
[3]Graham SV.Human papillomavirus E2 protein:linking replication,transcription,and RNA processing[J].Journal of Virology,2016,90(19):8384-8388.
[4]王金桃,丁玲,高尔生,等.人乳头瘤病毒16 E2、E6癌基因在子宫颈癌中的表达及E2缺失分析[J].中华流行病学杂志,2007,28(10):968-971.
[5]Kajitani N,Schwartz S.RNA binding proteins that control human papillomavirus gene expression[J].Biomolecules,2015,5(2):758-774.
[6]Ghanem LR,Chatterji P,Liebhaber SA.Specific enrichment of the RNA-binding proteins PCBP1 and PCBP2 in chief cells of the murine gastric mucosa[J].Gene Expression Patterns,2014,14(2):78-87.
[7]Graham SV,Faizo AA.Control of human papillomavirus gene expression by alternative splicing[J].Virus Research,2017,231(SI):83-95.
[8]Wu CJ,Kajitani N,Schwartz S.Splicing and polyadenylation of human papillomavirus type 16 m RNAs[J].International Journal of Molecular Sciences,2017,18(2):E366.
[9]Pillai MR,Chacko P,Kesari L,et al.Expression of folate receptors and heterogeneous nuclear ribonucleoprotein E1 in women with human papillomavirus mediated transformation of cervical tissue to cancer[J].Journal of Clinical Pathology,2003,56(8):569-574.
[10]Pathak S,Bajpai D,Banerjee A,et al.Serum One-Carbon metabolites and risk of cervical cancer[J].Nutrition and Cancer-An International Journal,2014,66(5):818-824.
[11]Macdonald OK,Chen J,Dodson M,et al.Prognostic significance of histology and positive lymph node involvement following radical hysterectomy in carcinoma of the cervix[J].American journal of clinical oncology,2009,32(4):411-416.
[12]王丽双,毛原夫,杨晶,等.CINⅠ、CINⅡ及CINⅢ发病高危因素的多因素Logistic回归分析[J].河北医科大学学报,2012,33(11):1315-1317.
[13]Collins S,Rollason TP,Young LS,et al.Cigarette smoking is an Independent risk factor for cervical intraepithelial neoplasia in young women:a longitudinal study[J].European journal of cancer(Oxford,England:1990),2010,46(2):405-411.
[14]Mclntyre-Seltman K,Castle PE,Guido R,et al.Smoking is a risk factor for cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology[J].Cancer Epidemiology,Biomarkers&Prevention,2005,14(5):1165-1170.
[15]Chaudhury A,Chander P,Howe PH.Heterogeneous nuclear ribonucleoproteins(hnRNPs)in cellular processes:focus on hnRNP E1's multifunctional regulatory roles[J].RNA(New York,N.Y.),2010,16(8):1449-1462.
[16]Li J,Feng Q,Wei X,et al.Micro RNA-490 regulates lung cancer metastasis by targeting poly r(C)-binding protein 1[J].Tumor Biology,2016,37(11):15221-15228.
[17]Zhang MP,Wang X,Tan J,et al.Poly r(C)binding protein(PCBP)1is a negative regulator of thyroid carcinoma[J].American journal of translational research,2016,8(8):3567-3573.
[18]Zhang MP,Zhang WS,Tan J,et al.Poly r(C)binding protein(PCBP)1 expression is regulated at the post-translation level in thyroid carcinoma[J].American journal of translational research,2017,9(2):708-714.
[19]Zeng Z,Yang H,Li Z,et al.Prevalence and genotype distribution of HPV infection in China:analysis of 51,345 HPV genotyping results from China's largest CAP certified laboratory[J].Journal of Cancer,2016,7(9):1037-1043.
[20]Kjaer SK,Munk C,Junge J,et al.Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology,ASCUS/LSIL,HSIL,or cervical cancer:what is the potential for prevention?[J].Cancer Causes&Control,2014,25(2):179-189.
[21]Egawa N,Egawa K,Griffin H,et al.Human papillomaviruses;epithelial tropisms,and the development of neoplasia[J].Viruses,2015,7(7):3863-3890.
[22]Vogt M,Butz K,Dymalla S,et al.Inhibition of Bax activity is crucial for the antiapoptotic function of the human papillomavirus E6 oncoprotein[J].Oncogene,2006,25(29):4009-4015.
[23]Collier B,Goobar-Larsson L,Sokolowski M,Schwartz S.Translational inhibition in vitro of human papillomavirus type 16 L2 m RNAmediated through interaction with heterogeneous ribonucleoprotein Kand poly(r C)-binding protein 1 and 2[J].Journal of Biological Chemistry,273(35):22648-22656.