微小核醣核酸(microRNA/miRNA)是一段長度約為22 核苷酸的寡核醣
核酸分子，它們可以藉由調控mRNA來抑制轉譯作用或是造成mRNA的降
解來降低基因的表現。近來有許多研究發現，miRNA與癌症具有高度的相
關性。因此推論miRNA可能是癌化過程的一個導因。到目前為止，在人體
上有超過700個miRNA被發現，而大約有100左右的miRNA被確認與人類癌
症具有相關性，這其中包含有乳癌、血癌、肺癌、直腸癌、腦癌和肝癌。
不過，對於大部分的miRNA在人類癌症所扮演的角色仍需進一步印證。本
篇研究主要要探討與攝護腺癌及食道癌相關的miRNAs分別在攝護腺癌及
食道癌癌化過程中所扮演的角色。在攝護腺癌細胞中，我們發現miR-330
在攝護腺癌細胞株中的表現與正常攝護腺細胞株作比較，有明顯下降的現
象。進一步，利用生物資訊學方法和luciferase reporter assay，我們發現miR-330的調控蛋白質為E2F1。分析攝護腺癌細胞株與攝護腺癌臨床組織中，E2F1蛋白質的表現，我們發現E2F1蛋白質的表現的確與miR-330的表
現，有相反的趨勢。為了瞭解miR-330在細胞中的調控機轉，我們在攝護
腺癌細胞株中過渡表現miR-330，結果發現miR-330可以藉由抑制E2F1的表
現間接抑制Akt的磷酸化，而促使細胞的生長被抑制，進而誘導細胞凋亡。
在食道癌細胞中，我們發現抑癌蛋白質-LATS2的表現受到miR-373所抑制
並且在食道癌細胞株與食道癌臨床組織中，LATS2與miR-373的表現有相反
的趨勢。我們也發現在食道癌細胞中抑制或過度表現miR-373，細胞的生
長會受到影響。綜合上述結果，我們發現miR-330和miR-373均可以透過調
控其target proteins來影響攝護腺癌細胞及食道癌細胞的生長。另外，此研究也提供將來在臨床上治療攝護腺癌和食道癌的新方向。

MicroRNAs (miRNAs) are 22-nucleotide sequences that interact with multiple mRNAs resulting in either translational repression or degradation. A number of
studies have demonstrated that deregulation of miRNAs associates with cancer development and tumorigenesis. So far, the number of human miRNAs has been reported in excess of 700 and about one hundred miRNAs have been demonstrated to associate with various cancer development including breast cancer, leukemia, lung cancer, colon cancer, brain cancer and liver cancer. But, the roles of most miRNAs in tumorigenesis remained to be clarified. This study aimed to investigate the roles of prostate cancer related miRNAs and esophageal cancer related miRNAs in prostate and esophageal cancers tumorigenesis. In prostate cancer, we demonstrated that miR-330 was significantly lower expressed in human prostate cancer cell lines than in nontumorigenic prostate epithelial cells. Bioinformatics analyses and luciferase reporter assay reveal that one of target of miR-330 was E2F1. The expression level of miR-330 and E2F1 was inversely correlated in cell lines and prostate cancer specimens. After overexpressing of miR-330 in PC-3 cells, cell growth was suppressed by reducing E2F1-mediated Akt phosphorylation and thereby inducing apoptosis. In esophageal cancer, we found that large tumor suppressor, homolog 2 (LATS2) protein expression was mediated by miR-373 at the post-transcriptional level and inversely correlated with miR-373 amounts in esophageal cancer. The direct inhibition of LATS2 protein was mediated by miR-373 and manipulated the expression of miR-373 to affect esophageal cancer cells growth. These evidences suggest the important roles of prostate cancer and esophageal cancer-related miRNAs in tumorgenesis by regulating their target protein expression. And this highlight these
miRNAs or their targets may be as new therapeutic targets for prostate cancer and esophageal cancer in the future.

台灣地區主要死因分析（2008），行政院衛生署統計資料
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