本文選題：miR-1246 + 宮頸癌�。� 參考：《中南大學(xué)》2014年碩士論文

【摘要】：宮頸癌是嚴(yán)重影響婦女健康的一種惡性腫瘤,其發(fā)病率僅次于乳腺癌。其主要的發(fā)病原因是持續(xù)性的高危型人乳頭狀瘤病毒(HPV)感染。HPVE6早期調(diào)控基因主要與HPV的致癌性相關(guān),編碼其重要的致癌蛋白。MicroRNAs是一類長度為17-25nt的非編碼RNA分子,通過與下游靶基因的3’端非翻譯區(qū)結(jié)合,抑制翻譯過程,從而調(diào)控蛋白編碼基因的轉(zhuǎn)錄后翻譯。近年來的研究表明microRNAs廣泛參與包括癌癥在內(nèi)的各種疾病發(fā)生發(fā)展,可以作為疾病的診斷、預(yù)后的分子標(biāo)志以及潛在的治療靶點。MicroRNAs可以通過影響癌細胞的增殖、遷移、侵襲、細胞周期與凋亡等過程參與癌癥的發(fā)生發(fā)展過程。MicroRNA-1246(miR-1246)定位于人2號染色體上,其表達受抑癌蛋白p53調(diào)控,參與唐氏綜合癥、系統(tǒng)性紅斑狼瘡等的發(fā)病過程。本文主要對miR-1246與宮頸癌發(fā)生機制的相關(guān)性進行研究。 本文首先利用實時熒光定量PCR的方法,比較了68例宮頸癌組織及52例對照樣本的miR。1246的表達水平,分析了miR-1246的表達水平與臨床病理特征的關(guān)系。結(jié)果表明：宮頸癌組織中的miR-1246的表達水平顯著低于對照組(p0.05),miR-1246的低表達與臨床分期相關(guān)(p0.05),與年齡、腫瘤直徑、宮頸浸潤深度、淋巴結(jié)轉(zhuǎn)移、脈管浸潤無關(guān)(p0.05)。 由于發(fā)現(xiàn)miR-1246在HPV16感染的宮頸癌組織及細胞系中比在HPV16未感染的宮頸癌組織及細胞系中的表達水平低。因此,我們利用過表達和(或)基因沉默癌細胞系(株)中的HPV16E6等方法,探討了HPV16E6致癌蛋白與miR-1246表達之間的關(guān)系。結(jié)果表明：HPV16(+)宮頸癌細胞系SiHa中,敲除掉HPV16E6后,miR-1246表達上調(diào),其下游靶蛋白DYRK1A表達降低；而HPV16(-)宮頸癌細胞系C33A轉(zhuǎn)染HPV16E6后,miR-1246表達下調(diào),其下游靶蛋白DYRK1A表達升高。表明HPV16E6致癌蛋白對miR-1246有明顯的負(fù)調(diào)控作用。 本文進一步采用模擬體內(nèi)成熟miR-1246及siRNA干擾內(nèi)源性miR-1246等方法研究了miR-1246對C33A細胞增殖、遷移、細胞周期的影響。結(jié)果發(fā)現(xiàn)miR-1246對宮頸癌細胞系C33A的增殖和細胞周期無顯著影響,但對其細胞遷移能力有一定影響。
[Abstract]:Cervical cancer is a malignant tumor that seriously affects women's health, its incidence is second only to breast cancer. The main cause is the persistent high risk HPV infection. The early regulatory gene of HPVE6 is mainly related to the carcinogenicity of HPV. MicroRNAs, an important carcinogenic protein, are a class of non-coding RNA molecules with length of 17-25nt. By binding to the 3 '-terminal untranslated region of the downstream target gene, the process of translation was inhibited and the post-transcriptional translation of the protein encoding gene was regulated. Recent studies have shown that microRNAs is widely involved in the occurrence and development of various diseases, including cancer, and can be used as a molecular marker of disease diagnosis, prognosis and potential therapeutic target. MicroRNAs can affect the proliferation, migration and invasion of cancer cells. Cell cycle and apoptosis. MicroRNA-1246 miR-1246) is located on human chromosome 2. Its expression is regulated by tumor suppressor protein p53 and participates in the pathogenesis of Down's syndrome and systemic lupus erythematosus. The relationship between miR-1246 and the mechanism of cervical cancer was studied in this paper. The expression of miR.1246 in 68 cases of cervical carcinoma and 52 cases of control were compared by real-time fluorescence quantitative PCR. The relationship between the expression of miR-1246 and clinicopathological features was analyzed. The results showed that the expression of miR-1246 in cervical carcinoma was significantly lower than that in control group. The low expression of miR-1246 was correlated with clinical stage, age, tumor diameter, depth of cervix invasion, lymph node metastasis and vascular invasion. It was found that the expression of miR-1246 in HPV16 infected cervical cancer tissues and cell lines was lower than that in HPV16 uninfected cervical cancer tissues and cell lines. Therefore, we studied the relationship between HPV16E6 oncoprotein and miR-1246 expression by using overexpression and / or gene silencing of HPV16E6 in cancer cell lines (lines). The results showed that the expression of miR-1246 was up-regulated and the expression of downstream target protein DYRK1A was decreased after knockout of HPV16E6 in the cervical cancer cell line SiHa, while the expression of miR-1246 was down-regulated and the expression of DYRK1A in the downstream target protein was increased after transfection of C33A into the cervical cancer cell line C33A. The results showed that HPV16E6 oncoprotein had a negative effect on miR-1246. The effects of miR-1246 on the proliferation, migration and cell cycle of C33A cells were further studied by simulating mature miR-1246 in vivo and interfering with endogenous miR-1246 by siRNA. The results showed that miR-1246 had no significant effect on the proliferation and cell cycle of cervical cancer cell line C33A, but had a certain effect on the migration ability of cervical cancer cell line C33A.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33

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本文編號：1835982