MiR-125a调控宫颈癌生长和转移的功能研究

发布时间：2018-06-21 09:26

本文选题：miR-125a + 宫颈癌　；参考：《中国人民解放军医学院》2016年博士论文

【摘要】：宫颈癌是女性生殖系统的常见肿瘤,在女性恶性肿瘤发病率位于第三位,死亡率位于第四位。其中80%的病例发生于发展中国家。虽然放疗,化疗和手术治疗已经成为进展期病人标准的治疗方案,但其5年生存率仍不理想。淋巴结和远处脏器的转移是治疗失败的主要原因,因此阐述宫颈癌发生发展的分子机制成为其个性化治疗的重要依据。就宫颈癌的发生而言,现在普遍接受的研究理论为：其发生发展与HPV感染有重要的关系。然而研究发现HPV感染只是宫颈癌发生的必要因素并不是充分因素,还涉及多种基因的改变。而这些引起宫颈癌发生发展的基因改变的研究还比较少。miRNA是一类非编码小RNA,其可以结合于靶基因mRNA的3’-非翻译区(untranslated region, UTR)进而抑制靶基因的表达。最新的研究发现miRNA介导的转录后调控基因表达异常在多种癌症的发生发展中起重要的作用,其中也包括宫颈癌。研究还发现miRNA在癌组织和癌旁组织表达存在差异,这种差异也使得miRNA成为潜在的治疗和预测靶点。MiR-125a已经证实是一种新的抑癌基因,在多种癌组织中检测到其表达降低,然而其与宫颈癌的关系还没有报道。我们研究发现,miR-125a在宫颈癌组织中表达明显低于癌旁组织。体外实验发现miR-125a可以明显的抑制细胞周期进而抑制宫颈癌细胞的生长转移,我们在动物模型中也得到了相同的结论。进一步研究我们发现STAT3 是 miR-125a的新的靶基因,miR-125a可以直接结合于STAT3的3’非编码区进而抑制该基因的表达。综上所述,过表达miR-125a可能成为STAT3异常激活宫颈癌患者的精准有效的治疗方案。
[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.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.33

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