本文選題：miR-125a + 宮頸癌　； 參考：《中國人民解放軍醫(yī)學(xué)院》2016年博士論文

【摘要】：宮頸癌是女性生殖系統(tǒng)的常見腫瘤,在女性惡性腫瘤發(fā)病率位于第三位,死亡率位于第四位。其中80%的病例發(fā)生于發(fā)展中國家。雖然放療,化療和手術(shù)治療已經(jīng)成為進(jìn)展期病人標(biāo)準(zhǔn)的治療方案,但其5年生存率仍不理想。淋巴結(jié)和遠(yuǎn)處臟器的轉(zhuǎn)移是治療失敗的主要原因,因此闡述宮頸癌發(fā)生發(fā)展的分子機(jī)制成為其個性化治療的重要依據(jù)。就宮頸癌的發(fā)生而言,現(xiàn)在普遍接受的研究理論為：其發(fā)生發(fā)展與HPV感染有重要的關(guān)系。然而研究發(fā)現(xiàn)HPV感染只是宮頸癌發(fā)生的必要因素并不是充分因素,還涉及多種基因的改變。而這些引起宮頸癌發(fā)生發(fā)展的基因改變的研究還比較少。miRNA是一類非編碼小RNA,其可以結(jié)合于靶基因mRNA的3’-非翻譯區(qū)(untranslated region, UTR)進(jìn)而抑制靶基因的表達(dá)。最新的研究發(fā)現(xiàn)miRNA介導(dǎo)的轉(zhuǎn)錄后調(diào)控基因表達(dá)異常在多種癌癥的發(fā)生發(fā)展中起重要的作用,其中也包括宮頸癌。研究還發(fā)現(xiàn)miRNA在癌組織和癌旁組織表達(dá)存在差異,這種差異也使得miRNA成為潛在的治療和預(yù)測靶點。MiR-125a已經(jīng)證實是一種新的抑癌基因,在多種癌組織中檢測到其表達(dá)降低,然而其與宮頸癌的關(guān)系還沒有報道。我們研究發(fā)現(xiàn),miR-125a在宮頸癌組織中表達(dá)明顯低于癌旁組織。體外實驗發(fā)現(xiàn)miR-125a可以明顯的抑制細(xì)胞周期進(jìn)而抑制宮頸癌細(xì)胞的生長轉(zhuǎn)移,我們在動物模型中也得到了相同的結(jié)論。進(jìn)一步研究我們發(fā)現(xiàn)STAT3 是 miR-125a的新的靶基因,miR-125a可以直接結(jié)合于STAT3的3’非編碼區(qū)進(jìn)而抑制該基因的表達(dá)。綜上所述,過表達(dá)miR-125a可能成為STAT3異常激活宮頸癌患者的精準(zhǔn)有效的治療方案。
[Abstract]:Cervical cancer is a common tumor in the female reproductive system. Eighty percent of these cases occur in developing countries. Although radiotherapy, chemotherapy and surgery have become the standard treatment for advanced patients, the 5-year survival rate is still not satisfactory. Metastasis of lymph nodes and distant organs is the main cause of failure of treatment. Therefore, the molecular mechanism of cervical cancer development has become an important basis for individualized treatment. As far as the occurrence of cervical cancer is concerned, it is widely accepted that there is an important relationship between the occurrence and development of cervical cancer and HPV infection. However, the study found that HPV infection is a necessary factor in cervical cancer is not a sufficient factor, but also involves a variety of gene changes. However, there are few studies on the gene changes that cause the carcinogenesis and development of cervical cancer. MiRNA is a kind of non-coding small RNAs, which can bind to the 3 untranslated region (UTRs) of target gene mRNA and then inhibit the expression of target gene. Recent studies have found that miRNA-mediated abnormal expression of posttranscriptional genes plays an important role in the development of many cancers, including cervical cancer. The difference in miRNA expression in cancer tissues and adjacent tissues has also made miRNA a potential therapeutic and predictive target. MiR-125a has been proved to be a new tumor suppressor gene, and its expression has been detected to be reduced in many kinds of cancer tissues. However, its relationship with cervical cancer has not been reported. We found that the expression of miR-125a in cervical cancer tissues was significantly lower than that in paracancerous tissues. It was found that miR-125a could inhibit the cell cycle and then inhibit the growth and metastasis of cervical cancer cells in vitro. We also got the same conclusion in animal models. Furthermore, we found that STAT3, a new target gene of miR-125a, can directly bind to the 3'non-coding region of STAT3 and inhibit the expression of the gene. In conclusion, overexpression of miR-125a may be an accurate and effective therapy for abnormal activation of STAT3 in patients with cervical cancer.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R737.33

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1 范忠義;MiR-125a調(diào)控宮頸癌生長和轉(zhuǎn)移的功能研究[D];中國人民解放軍醫(yī)學(xué)院;2016年

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