IEX-1在宮頸癌中的表達(dá)及其與HPV感染的相關(guān)性
發(fā)布時(shí)間：2018-09-10 16:31
【摘要】：背景和目的子宮頸癌是女性生殖系統(tǒng)最常見的惡性腫瘤之一,全球范圍內(nèi)宮頸癌發(fā)病率在女性癌癥中占第三,僅次于肺癌和胃癌,約有90%的宮頸癌死亡病例發(fā)生在發(fā)展中國(guó),嚴(yán)重威脅著女性生命健康。宮頸癌最主要的兩種類型是鱗狀細(xì)胞癌(squamous cell carcinoma,SCC)和腺癌(adenocarcinoma,ADCA),宮頸鱗癌約占80%左右,近年來宮頸腺癌的發(fā)病率不斷增加。持續(xù)的高危型人乳頭瘤病毒(high risk human papilloma virus,HR-HPV)感染是宮頸癌最主要的致癌因子,其中HPV16和HPV18是最常見的HR-HPV型別。早期蛋白E6和E7是HR-HPV的主要癌蛋白,E6可泛素化水解P53,導(dǎo)致P53依賴的細(xì)胞凋亡和/或衰老的損失,而E7結(jié)合p RB從而導(dǎo)致細(xì)胞周期紊亂。因此,HR-HPV感染可導(dǎo)致細(xì)胞的惡性轉(zhuǎn)化和腫瘤的發(fā)展。1993年Charles等在小鼠成纖維細(xì)胞中發(fā)現(xiàn)了即刻早期反應(yīng)基因(Immediate early response gene X-1,IEX-1),作為即刻早期基因(immediate early gene,IEG)一員,IEX-1可以在多種刺激條件下短暫快速地表達(dá)。這些刺激因子包括生長(zhǎng)因子、細(xì)胞因子、電離輻射、病毒感染和其他類型的細(xì)胞應(yīng)激因素。IEX-1參與細(xì)胞的代謝、增殖、凋亡、分化及細(xì)胞周期調(diào)節(jié)等多種生物學(xué)效應(yīng)。IEX-1在調(diào)節(jié)細(xì)胞周期和凋亡過程中發(fā)揮著復(fù)雜的作用。雖然目前研究已經(jīng)證實(shí)在多種人類惡性腫瘤中IEX-1表達(dá)失調(diào),但在宮頸癌中IEX-1的研究較少,IEX-1在宮頸癌中的表達(dá)情況如何,IEX-1表達(dá)與宮頸HPV感染是否相關(guān)尚不清楚。本研究將通過免疫組化法分析IEX-1在宮頸癌組織、宮頸上皮內(nèi)瘤變(Cervical Intraepithelial Neoplasia,CIN)組織及正常宮頸組織中的表達(dá)情況,分析IEX-1的表達(dá)與宮頸癌臨床病理關(guān)系,預(yù)測(cè)IEX-1在宮頸癌發(fā)生發(fā)展中的作用。并通過實(shí)時(shí)熒光定量PRC(RT-q PCR)法及Western Blot法分析不同HPV感染狀態(tài)的宮頸癌細(xì)胞中IEX-1的表達(dá)差異。RNA干擾(RNA interference,RNAi)是指在進(jìn)化過程中高度保守的、由雙鏈RNA(double-stranded RNA,ds RNA)誘發(fā)的、同源m RNA高效特異性降解的現(xiàn)象。RNAi法具有高度的序列專一性,通過瞬時(shí)轉(zhuǎn)染si RNA導(dǎo)入細(xì)胞可以特異地使特定基因沉默。我們通過設(shè)計(jì)針對(duì)HPV16 E6的si RNA,轉(zhuǎn)染Si Ha細(xì)胞,特異性沉默Si Ha細(xì)胞中E6的表達(dá),檢測(cè)沉默E6前后Si Ha細(xì)胞中IEX-1的表達(dá),以探索IEX-1的表達(dá)與HPV感染的相關(guān)性及其可能涉及的機(jī)制。本課題將為明確宮頸癌變過程中IEX-1的作用及研究其與HPV的相互作用提供理論依據(jù)。材料與方法1.人宮頸癌細(xì)胞株Si Ha(HPV16+)、He La(HPV18+)、C-33a(HPV-)均由華中科技大學(xué)惠贈(zèng)。收集2010年1月到2014年10月在鄭州大學(xué)第一附屬醫(yī)院病理科存檔蠟塊標(biāo)本132份(其中手術(shù)標(biāo)本124例,活檢標(biāo)本8例)。其中正常宮頸29例,年齡32-61歲;CIN 46例(Ⅰ級(jí)19例、Ⅱ級(jí)17例、Ⅲ級(jí)10例),年齡29-58歲;宮頸癌57例(鱗癌35例、腺癌22例),年齡27-65歲。宮頸癌根據(jù)FIGO臨床病例分期:Ⅰ期23例,Ⅱ期26例,Ⅲ期6例,Ⅳ期2例。分化等級(jí):高分化13例,中分化18例,低分化26例。2.免疫組化SP法檢測(cè)IEX-1在正常宮頸組織、CIN組織及宮頸癌組織中的表達(dá)情況,并分析其與臨床病理特征的關(guān)系。3.以RT-q PCR法檢測(cè)Si Ha、He La、C-33a宮頸癌細(xì)胞系中IEX-1表達(dá),Western Blot法檢測(cè)Si Ha、He La、C-33a宮頸癌細(xì)胞系中IEX-1蛋白質(zhì)表達(dá)。4.RT-q PCR和Western Blot法檢測(cè)E6特異性si RNA干擾Si Ha細(xì)胞前后Si Ha細(xì)胞中E6及IEX-1的m RNA及蛋白表達(dá)水平。5.統(tǒng)計(jì)學(xué)處理:采用SPSS17.0軟件統(tǒng)計(jì)分析,定性資料比較采用卡方檢驗(yàn),定量資料比較采用單因素方差分析,以P0.05為差異有統(tǒng)計(jì)學(xué)意義。兩兩比較采用Bonferroni法檢驗(yàn)矯正檢驗(yàn)系數(shù)。結(jié)果1.免疫組化法顯示:IEX-1在正常宮頸組織、CIN組織和宮頸癌組織中的表達(dá)依次減少,三者之間差異有統(tǒng)計(jì)學(xué)意義(c2=75.905,P=0.0000.017)。IEX-1在宮頸癌組織中的表達(dá)與患者年齡、病理類型及FIGO分期均無關(guān)(均P0.05)。IEX-1的表達(dá)與宮頸癌分化程度及肌層浸潤(rùn)深度相關(guān)。分化程度越低,IEX-1蛋白陽(yáng)性表達(dá)率越低(c2=6.642,P=0.0090.05);深肌層浸潤(rùn)者IEX-1蛋白陽(yáng)性表達(dá)率明顯低于僅淺肌層浸潤(rùn)者(c2=5.076,P=0.0250.05)。2.RT-q PCR法分別檢測(cè)Si Ha細(xì)胞、He La細(xì)胞和C-33a細(xì)胞中IEX-1 m RNA表達(dá)水平顯示:IEX-1 m RNA在C-33a細(xì)胞中表達(dá)(21.652±9.020)高于Si Ha細(xì)胞(1.006±0.027)和He La細(xì)胞(1.742±0.854)(PSi Ha-C-33a=0.0030.05,PHe La-C-33a=0.0030.05)。Si Ha細(xì)胞和He La細(xì)胞間IEX-1m RNA表達(dá)無明顯差異(PSi Ha-He La=0.8680.05)。3.Western Blot法分別檢測(cè)Si Ha細(xì)胞、He La細(xì)胞和C-33a細(xì)胞中IEX-1蛋白的表達(dá)水平顯示:IEX-1蛋白在C-33a細(xì)胞(18.017±1.351)中表達(dá)高于Si Ha細(xì)胞(1.028±0.039)和He La細(xì)胞(2.004±0.363)(PSi Ha-C-33a0.001,PHe La-C-33a0.001)。Si Ha細(xì)胞和He La細(xì)胞間IEX-1蛋白表達(dá)無明顯差異(PSi Ha-He La=0.1520.05)。4.將Si Ha細(xì)胞分為干擾組、陰性對(duì)照組和空白對(duì)照組,干擾組轉(zhuǎn)染入E6特異性Si RNA核苷酸序列,陰性對(duì)照組轉(zhuǎn)入無義RNA核苷酸序列,空白對(duì)照組使用RNase-free water代替。轉(zhuǎn)染后用RT-q PCR法分別檢測(cè)干擾組、陰性對(duì)照組和空白對(duì)照組E6 m RNA和IEX-1 m RNA表達(dá)水平顯示:E6 m RNA在干擾組(0.218±0.106)表達(dá)水平明顯低于陰性對(duì)照組(1.031±0.072)及空白對(duì)照組(1.003±0.015)(P干擾-陰性對(duì)照0.001,P干擾-空白對(duì)照0.001),E6 m RNA表達(dá)水平在陰性對(duì)照組和空白對(duì)照組差異無統(tǒng)計(jì)學(xué)意義(P陰性對(duì)照-空白對(duì)照=0.2070.05)。IEX-1m RNA在干擾組(20.083±0.672)表達(dá)水平明顯高于陰性對(duì)照組(1.613±0.408)及空白對(duì)照組(1.018±0.032)(P干擾-陰性對(duì)照0.001,P干擾-空白對(duì)照0.001),IEX-1 m RNA表達(dá)水平在陰性對(duì)照組和空白對(duì)照組差異無統(tǒng)計(jì)學(xué)意義(P陰性對(duì)照-空白對(duì)照=0.3040.05)5.轉(zhuǎn)染后用Western Blot法分別檢測(cè)干擾組、陰性對(duì)照組和空白對(duì)照組E6、IEX-1蛋白表達(dá)水平顯示:E6蛋白在干擾組(0.184±0.274)表達(dá)水平均明顯低于陰性對(duì)照組(0.692±0.133)及空白對(duì)照組(0.783±0.097)(P干擾-陰性對(duì)照0.001,P干擾-空白對(duì)照0.001),E6蛋白表達(dá)水平在陰性對(duì)照組和空白對(duì)照組間差異無統(tǒng)計(jì)學(xué)意義(P陰性對(duì)照-空白對(duì)照=0.1840.05)。IEX-1蛋白在干擾組(0.672±0.135)表達(dá)水平均明顯高于陰性對(duì)照組(0.137±0.071)及空白對(duì)照組(0.081±0.009)(P干擾-陰性對(duì)照=0.0010.05,P干擾-空白對(duì)照0.001),IEX-1蛋白表達(dá)水平在陰性對(duì)照組和空白對(duì)照組間差異無統(tǒng)計(jì)學(xué)意義(P陰性對(duì)照-空白對(duì)照=0.0940.05)結(jié)論1.IEX-1在宮頸癌組織中表達(dá)減低,其表達(dá)水平與宮頸癌惡性程度呈負(fù)相關(guān),宮頸上皮細(xì)胞中IEX-1的表達(dá)減低或缺失可能參與了宮頸癌的發(fā)生與發(fā)展。2.IEX-1在宮頸癌細(xì)胞中的表達(dá)水平與HPV感染與否呈負(fù)相關(guān),與感染的HPV型別無關(guān),IEX-1與HPV在宮頸癌變過程中可能發(fā)揮相反作用。3.E6特異性Si RNA可沉默宮頸癌細(xì)胞系中E6蛋白的表達(dá)。宮頸癌細(xì)胞系中HPV E6沉默后,IEX-1表達(dá)上調(diào),HPV可能通過E6癌蛋白下調(diào)了IEX-1的表達(dá)。
[Abstract]:BACKGROUND AND OBJECTIVE Cervical cancer is one of the most common malignant tumors in the female reproductive system. The incidence of cervical cancer is the third in female cancers worldwide, next only to lung cancer and gastric cancer. About 90% of cervical cancer deaths occur in developing countries, which seriously threaten women's life and health. Squamous cell carcinoma (SCC) and adenocarcinoma (ADCA), cervical squamous cell carcinoma (SCC) account for about 80%, the incidence of cervical adenocarcinoma in recent years is increasing. Persistent high-risk human papilloma virus (HR-HPV) infection is the most important carcinogen of cervical cancer, HPV16 and HPV18 are the most common HR-HPV. Type. E6 and E7 are the major cancer proteins of HR-HPV. E6 can hydrolyze P53 by ubiquitination, leading to loss of apoptosis and/or senescence in P53-dependent cells. E7 binding to P RB leads to cell cycle disorders. Therefore, HR-HPV infection can lead to malignant transformation and tumor development. Charles et al. found in mouse fibroblasts in 1993 Immediate early response gene X-1 (IEX-1), as a member of immediate early gene (IEG), can be expressed briefly and rapidly under a variety of stimulation conditions. These stimulating factors include growth factors, cytokines, ionizing radiation, virus infection and other types of cell stress factors. IEX-1 plays a complex role in regulating cell cycle and apoptosis. Although the expression of IEX-1 has been proved to be out of balance in many human malignant tumors, there is little research on IEX-1 in cervical cancer and IEX-1 in cervical cancer. The expression of IEX-1 in cervical cancer, cervical intraepithelial neoplasia (CIN) and normal cervical tissues was analyzed by immunohistochemistry. The relationship between IEX-1 expression and clinical pathology of cervical cancer was analyzed. To determine the role of IEX-1 in the development of cervical cancer, real-time fluorescence quantitative PRC (RT-q PCR) and Western Blot were used to analyze the expression of IEX-1 in cervical cancer cells with different HPV infection status. Homologous m RNA degrades efficiently and specifically. RNAi method has high sequence specificity. Specific gene silencing can be achieved by transient transfection of Si RNA into cells. Material and Methods 1. Human cervical cancer cell lines Si Ha (HPV16 +), He La (HPV18 +), C-33a (HPV -) were given by Huazhong University of Science and Technology. From January 2010 to October 2014, 132 cervical specimens (124 surgical specimens and 8 biopsy specimens) were collected from the Department of Pathology, First Affiliated Hospital of Zhengzhou University. Among them, 29 cases were normal cervix, aged 32-61 years; 46 cases of CIN (19 cases of grade I, 17 cases of grade II, 10 cases of grade III), aged 29-58 years; 57 cases of cervical cancer (35 cases of squamous cell carcinoma, 22 cases of adenocarcinoma), aged 27-65 years. According to FIGO clinical staging, 23 cases of cervical cancer were stage I, 26 cases of stage II, 6 cases of stage III and 2 cases of stage IV. Differentiation grade: 13 cases were well-differentiated, 18 cases were moderately differentiated and 26 cases were poorly differentiated. The expression of IEX-1 in Si Ha, He La, C-33a cervical cancer cell lines was detected by Western Blot method, and the expression of IEX-1 protein in Si Ha, He La, C-33a cervical cancer cell lines was detected by Western Blot method. Statistical analysis showed that the expression of IEX-1 in normal cervical tissues, CIN tissues and cervical cancer tissues decreased in turn. The expression of IEX-1 in cervical cancer tissues was not correlated with age, pathological type and FIGO stage (all P 0.05). The expression of IEX-1 was correlated with the degree of differentiation and the depth of myometrial invasion. The lower the degree of differentiation, the lower the positive expression rate of IEX-1 protein (c 2 = 6.642, P = 0.0090.05). The positive expression rate of IEX-1 protein in deep myometrial infiltrators was significantly lower than that in superficial myometrial infiltrators only (c2 = 5.076, P = 0.0250.05). 2. Detection of IEX-1 m RNA expression in Si Ha cells, He La cells and C-33a cells by RT-q PCR showed that the expression of IEX-1 m RNA in C-33a cells (21.652 + 9.020) was higher than that in Si Ha cells (1.006 + 0.027) and He La cells (1.742 + 0.027). 854 (PSi Ha-C-33a = 0.0030.05, PHe La-C-33a = 0.0030.05). There was no significant difference in IEX-1m RNA expression between Si Ha cells and He La cells (PSi Ha-He La = 0.8680.05). 3. Western Blot assay of IEX-1 protein expression in Si Ha cells, He La cells and C-33a cells showed that IEX-1 protein expression in C-33a cells was higher than that in Si Ha cells (18.017 + 1.351). There was no significant difference in IEX-1 protein expression between Si Ha cells and He La cells (PSi Ha-C-33a 0.001, PHe La-C-33a 0.001). 4. Si Ha cells were divided into interference group, negative control group and blank control group. The interference group was transfected into E6-specific Si RNA sequence, negative pair. After transfection, the expression levels of E6 m RNA and IEX-1 m RNA in the negative control group and blank control group were detected by RT-q PCR respectively. The expression levels of E6 m RNA and IEX-1 m RNA in the interference group (0.218 +0.106) were significantly lower than those in the negative control group (1.031 +0.072) and blank control group (1.031 +0.072). There was no significant difference in the expression of E6 m RNA between the negative control group and the blank control group (P-negative control = 0.2070.05). The expression of IEX-1m RNA in the interference group (20.083 + 0.672) was significantly higher than that in the negative control group (1.613 + 0.408) and the blank control group (0.001). There was no significant difference in the expression of IEX-1 m RNA between negative control group and blank control group (P-negative control = 0.3040.05). 5. Western Blot method was used to detect the expression of E6 and IEX-1 protein in interference group, negative control group and blank control group respectively. The level of E6 protein expression in the interference group (0.184+0.274) was significantly lower than that in the negative control group (0.692+0.133) and the blank control group (0.783+0.097) (P interference-negative control 0.001, P interference-blank control 0.001), and there was no significant difference between the negative control group and the blank control group (P negative control-blank control = 0.001). 1840.05). The expression level of IEX-1 protein in the interference group (0.672.135) was significantly higher than that in the negative control group (0.137.071) and the blank control group (0.081.009) (P interference-negative control = 0.0010.05, P interference-blank control 0.001). There was no significant difference in the expression level of IEX-1 protein between the negative control group and blank control group (P negative control-blank control-blank control). Conclusion 1. The expression of IEX-1 in cervical cancer tissues decreased, and its expression level was negatively correlated with the malignant degree of cervical cancer. The decrease or deletion of IEX-1 expression in cervical epithelial cells may be involved in the occurrence and development of cervical cancer. 2. The expression level of IEX-1 in cervical cancer cells was negatively correlated with HPV infection and H infection. IEX-1 and HPV may play an opposite role in cervical carcinogenesis. 3. E6-specific Si RNA can silence the expression of E6 protein in cervical cancer cell lines. After HPV E6 silencing, the expression of IEX-1 is up-regulated, and HPV may down-regulate the expression of IEX-1 through E6 oncoprotein.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R737.33
[Abstract]:BACKGROUND AND OBJECTIVE Cervical cancer is one of the most common malignant tumors in the female reproductive system. The incidence of cervical cancer is the third in female cancers worldwide, next only to lung cancer and gastric cancer. About 90% of cervical cancer deaths occur in developing countries, which seriously threaten women's life and health. Squamous cell carcinoma (SCC) and adenocarcinoma (ADCA), cervical squamous cell carcinoma (SCC) account for about 80%, the incidence of cervical adenocarcinoma in recent years is increasing. Persistent high-risk human papilloma virus (HR-HPV) infection is the most important carcinogen of cervical cancer, HPV16 and HPV18 are the most common HR-HPV. Type. E6 and E7 are the major cancer proteins of HR-HPV. E6 can hydrolyze P53 by ubiquitination, leading to loss of apoptosis and/or senescence in P53-dependent cells. E7 binding to P RB leads to cell cycle disorders. Therefore, HR-HPV infection can lead to malignant transformation and tumor development. Charles et al. found in mouse fibroblasts in 1993 Immediate early response gene X-1 (IEX-1), as a member of immediate early gene (IEG), can be expressed briefly and rapidly under a variety of stimulation conditions. These stimulating factors include growth factors, cytokines, ionizing radiation, virus infection and other types of cell stress factors. IEX-1 plays a complex role in regulating cell cycle and apoptosis. Although the expression of IEX-1 has been proved to be out of balance in many human malignant tumors, there is little research on IEX-1 in cervical cancer and IEX-1 in cervical cancer. The expression of IEX-1 in cervical cancer, cervical intraepithelial neoplasia (CIN) and normal cervical tissues was analyzed by immunohistochemistry. The relationship between IEX-1 expression and clinical pathology of cervical cancer was analyzed. To determine the role of IEX-1 in the development of cervical cancer, real-time fluorescence quantitative PRC (RT-q PCR) and Western Blot were used to analyze the expression of IEX-1 in cervical cancer cells with different HPV infection status. Homologous m RNA degrades efficiently and specifically. RNAi method has high sequence specificity. Specific gene silencing can be achieved by transient transfection of Si RNA into cells. Material and Methods 1. Human cervical cancer cell lines Si Ha (HPV16 +), He La (HPV18 +), C-33a (HPV -) were given by Huazhong University of Science and Technology. From January 2010 to October 2014, 132 cervical specimens (124 surgical specimens and 8 biopsy specimens) were collected from the Department of Pathology, First Affiliated Hospital of Zhengzhou University. Among them, 29 cases were normal cervix, aged 32-61 years; 46 cases of CIN (19 cases of grade I, 17 cases of grade II, 10 cases of grade III), aged 29-58 years; 57 cases of cervical cancer (35 cases of squamous cell carcinoma, 22 cases of adenocarcinoma), aged 27-65 years. According to FIGO clinical staging, 23 cases of cervical cancer were stage I, 26 cases of stage II, 6 cases of stage III and 2 cases of stage IV. Differentiation grade: 13 cases were well-differentiated, 18 cases were moderately differentiated and 26 cases were poorly differentiated. The expression of IEX-1 in Si Ha, He La, C-33a cervical cancer cell lines was detected by Western Blot method, and the expression of IEX-1 protein in Si Ha, He La, C-33a cervical cancer cell lines was detected by Western Blot method. Statistical analysis showed that the expression of IEX-1 in normal cervical tissues, CIN tissues and cervical cancer tissues decreased in turn. The expression of IEX-1 in cervical cancer tissues was not correlated with age, pathological type and FIGO stage (all P 0.05). The expression of IEX-1 was correlated with the degree of differentiation and the depth of myometrial invasion. The lower the degree of differentiation, the lower the positive expression rate of IEX-1 protein (c 2 = 6.642, P = 0.0090.05). The positive expression rate of IEX-1 protein in deep myometrial infiltrators was significantly lower than that in superficial myometrial infiltrators only (c2 = 5.076, P = 0.0250.05). 2. Detection of IEX-1 m RNA expression in Si Ha cells, He La cells and C-33a cells by RT-q PCR showed that the expression of IEX-1 m RNA in C-33a cells (21.652 + 9.020) was higher than that in Si Ha cells (1.006 + 0.027) and He La cells (1.742 + 0.027). 854 (PSi Ha-C-33a = 0.0030.05, PHe La-C-33a = 0.0030.05). There was no significant difference in IEX-1m RNA expression between Si Ha cells and He La cells (PSi Ha-He La = 0.8680.05). 3. Western Blot assay of IEX-1 protein expression in Si Ha cells, He La cells and C-33a cells showed that IEX-1 protein expression in C-33a cells was higher than that in Si Ha cells (18.017 + 1.351). There was no significant difference in IEX-1 protein expression between Si Ha cells and He La cells (PSi Ha-C-33a 0.001, PHe La-C-33a 0.001). 4. Si Ha cells were divided into interference group, negative control group and blank control group. The interference group was transfected into E6-specific Si RNA sequence, negative pair. After transfection, the expression levels of E6 m RNA and IEX-1 m RNA in the negative control group and blank control group were detected by RT-q PCR respectively. The expression levels of E6 m RNA and IEX-1 m RNA in the interference group (0.218 +0.106) were significantly lower than those in the negative control group (1.031 +0.072) and blank control group (1.031 +0.072). There was no significant difference in the expression of E6 m RNA between the negative control group and the blank control group (P-negative control = 0.2070.05). The expression of IEX-1m RNA in the interference group (20.083 + 0.672) was significantly higher than that in the negative control group (1.613 + 0.408) and the blank control group (0.001). There was no significant difference in the expression of IEX-1 m RNA between negative control group and blank control group (P-negative control = 0.3040.05). 5. Western Blot method was used to detect the expression of E6 and IEX-1 protein in interference group, negative control group and blank control group respectively. The level of E6 protein expression in the interference group (0.184+0.274) was significantly lower than that in the negative control group (0.692+0.133) and the blank control group (0.783+0.097) (P interference-negative control 0.001, P interference-blank control 0.001), and there was no significant difference between the negative control group and the blank control group (P negative control-blank control = 0.001). 1840.05). The expression level of IEX-1 protein in the interference group (0.672.135) was significantly higher than that in the negative control group (0.137.071) and the blank control group (0.081.009) (P interference-negative control = 0.0010.05, P interference-blank control 0.001). There was no significant difference in the expression level of IEX-1 protein between the negative control group and blank control group (P negative control-blank control-blank control). Conclusion 1. The expression of IEX-1 in cervical cancer tissues decreased, and its expression level was negatively correlated with the malignant degree of cervical cancer. The decrease or deletion of IEX-1 expression in cervical epithelial cells may be involved in the occurrence and development of cervical cancer. 2. The expression level of IEX-1 in cervical cancer cells was negatively correlated with HPV infection and H infection. IEX-1 and HPV may play an opposite role in cervical carcinogenesis. 3. E6-specific Si RNA can silence the expression of E6 protein in cervical cancer cell lines. After HPV E6 silencing, the expression of IEX-1 is up-regulated, and HPV may down-regulate the expression of IEX-1 through E6 oncoprotein.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R737.33
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