Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/92233
標題: Functional Characterization of Oncogenic Genes miR-372 and PARVA in Lung Cancer
功能性分析miR-372以及PARVA肺癌致癌基因
作者: 黃艾慧
Ay-Huey Huang
關鍵字: 肺癌;致癌基因;miR-372;PARVA
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摘要: 
Lung cancer is the most common cause of cancer deaths in the world. Several crucial steps of cancer progression are out of control determined by gene alterations including genetic mutations, epigenetic aberration and ablation of genes expression, leading to malignant tumorigenesis and metastasis which is pivotal to patients' survival. To understand the molecular mechanisms of cancer metastasis, it is indispensable to identify the genes whose alterations and expression are required for metastatic potentiality in cancer cells during cancer progression. We further investigated and identified the roles of miR-372 and PARVA in lung cancer. miR-372 was found to be a prognostic biomarker for the prediction of cancer relapse and survival in non-small cell lung cancer patients independent of stage or histological type. Here, we demonstrated that miR-372 was involved in the regulation of enhancing lung cancer metastasis in vivo and in vitro by multiply targeting to PTEN-STAT3-TIMP-1 axis. As an oncogene, PARVA, was firstly characterized in the lung cancer of promoting tumorigenesis, metastasis and angiogenesis by interacting with ILK followed by the activation of Akt and inhibition of GSK3. In conclusion, two oncogenes play significant roles in lung cancer progression by each individual pathway regulation and may further serve as potential therapeutic targets.

目前全世界發病率和導致死亡率最高的癌症是肺癌。癌症進程失去正常調控的幾個關鍵步驟通常都經由基因變異,包括基因突變、不正常的基因表徵遺傳調節和基因表現而導致惡性的腫瘤增生和癌轉移,其中癌轉移對病人的存活最為關鍵。為了進一步了解癌症轉移的分子機制,辨識出可能促進癌轉移的基因是極為重要的。在此,我們進一步探討並辨識出兩個致癌基因在肺癌中扮演的角色,包括miR-372和PARVA基因。前人研究發現,針對癌症復發預測與不同肺癌時期或病理組織型態之非小細胞肺癌病人的存活率,miR-372可作為其預後標記。在本研究中,我們發現miR-372參與調控PTEN-STAT3-TIMP-1的途徑中,並藉由多標的基因的抑制方式促進肺癌轉移的能力。另一個致癌基因,PARVA第一次在肺癌進程研究當中釐清其致癌的功能與角色。PARVA透過和ILK的交互作用和活化ILK,導致下游基因Akt的活化和GSK3的抑制,進而促進腫瘤增生、癌轉移與血管新生的能力。總而言之,這兩個致癌基因經由個別的調控路徑因而加速肺癌的進程,在治療癌症的應用上可作為有潛力的治療性標靶基因。
URI: http://hdl.handle.net/11455/92233
Rights: 同意授權瀏覽/列印電子全文服務,2018-08-28起公開。
Appears in Collections:分子生物學研究所

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