分析微小核糖核酸與標的基因發現癌轉移的調控機制

Interacting Analysis between microRNA and its Target Genes to Discover Metastasis Regulatory Mechanism

章雅雯(Ya-Wun Jhang)

指導教授 ： 李元綺

臺北醫學大學/醫學科技學院/醫學資訊研究所/碩士(2015年)

摘要

微小核糖核酸，是一個小片段髮夾型之RNA，內生性的存在於動植物以及病毒基因體中。微小核醣核酸在細胞中是由 RNA聚合脢II 所轉錄出來的，並經由 Drosha, Dicer 和RISC複合體的作用, 最後成為長度約為 22 核苷酸長的有功能性的寡核醣核酸。微小核糖核酸在體內藉由抑制轉譯或是 mRNA 的降解，來負調控下游基因的表現。有研究指出許多微小核醣核酸之下游基因的功能是調控細胞的生長、分化或是凋亡。
大多數的癌症死亡的主要原因是因為腫瘤轉移。而最近的研究顯示，微小核糖核酸在惡性腫瘤：如乳腺癌，肝癌，前列腺癌和大腸癌的侵襲和轉移扮演了重要的角色。本研究利用高通量生物晶片資料，結合有轉移能力的惡性腫瘤、與不會轉移的良性腫瘤，子宮內膜異位到卵巢的細胞、與正常的子宮內膜細胞找出促癌轉移基因與抑制癌轉移基因，後續利用生物資訊方式分析出它們的上游 microRNA，以及隱藏的下游microRNA, 希望未來可以進一步應用在臨床癌症治療上，降低病患死亡率。

關鍵字

子宮內膜異位、癌轉移、微小核糖核酸

並列摘要

MicroRNAs (miRNAs) are small hairpin-shaped, endogenous RNAs encoded in the genomes of plants, animals and virus. They are transcribed by RNA polymerase II and are processed to mature functional miRNAs (~22mer) by a series of processing of Drosha, Dicer and RISC. miRNA negatively regulates its target genes by either translational repression or mRNA cleavage. Previous studies have indicated that the functions of target genes of miRNAs are involved in cell growth, differentiation or apoptosis.

Metastases are the major cause of death from cancer. Recent studies have shown that microRNAs play an important role in invasion and metastasis of several malignancies, such as breast, liver, prostate and colorectal cancers. The study herein is to combine high throughput gene expression microarray data of metastatic tumor v.s. benign tumor and ovarian endometriosis v.s. endometrial tissues to find the “migration promoting genes” (MPG) and “migration suppressor genes” (MSG). With these genes, we could identify the upstream common miRNAs and the hidden downstream microRNAs using bioinformatics approaches. It is the hope that these discoveries are useful in cancer therapy and treatment and then decreasing the mortality rate in the near future.

並列關鍵字

Endometriosis , Metastasis , microRNA

參考文獻

Lee, Y., Kim, M., Han, J., Yeom, K. H., Lee, S., Baek, S. H., & Kim, V. N. (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J, 23(20), 4051-4060. doi: 10.1038/sj.emboj.7600385

Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E., & Kutay, U. (2004). Nuclear export of microRNA precursors. Science, 303(5654), 95-98. doi: 10.1126/science.1090599

Yu, S. L., Chen, H. Y., Chang, G. C., Chen, C. Y., Chen, H. W., Singh, S., . . . Yang, P. C. (2008). MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell, 13(1), 48-57. doi: 10.1016/j.ccr.2007.12.008

Adammek, M., Greve, B., Kassens, N., Schneider, C., Bruggemann, K., Schuring, A. N., . . . Gotte, M. (2013). MicroRNA miR-145 inhibits proliferation, invasiveness, and stem cell phenotype of an in vitro endometriosis model by targeting multiple cytoskeletal elements and pluripotency factors. Fertil Steril. doi: 10.1016/j.fertnstert.2012.11.055

Barad, O., Meiri, E., Avniel, A., Aharonov, R., Barzilai, A., Bentwich, I., . . . Einat, P. (2004). MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res, 14(12), 2486-2494. doi: 10.1101/gr.2845604