探討MicroRNA-21 在黑色素細胞癌中調控PTEN PDCD4之表現

Studying the role of microRNA-21 in PTEN and PDCD4 expression in melanoma

謝雅如(Hsieh Ya Ju)

指導教授 ： 李婉若

臺北醫學大學/醫學院/臨床醫學研究所/碩士(2014年)

https://doi.org/10.6831/TMU.2014.00008

摘要

黑色素細胞癌是具高度轉移性的惡性腫瘤，其惡性變化程度與基因異常有關聯。包括了黑色素細胞癌，在許多癌症發現抑癌基因PTEN (phosphatase and tensin homology) 與PDCD4 (programmed cell death 4) 表現量下降與癌症的轉移有關。同時在許多癌症已被發現PTEN 與PDCD4 是微小核糖核酸-21的目標，會受到微小核糖核酸-21的抑制；而微小核糖核酸-21會在黑色素細胞癌過度表現，但是在黑色素細胞癌中，是否藉由微小核糖核酸-21去抑制 PTEN 與PDCD4而造成轉移仍未明。本研究假設核糖核酸-21透過抑制 PTEN 與PDCD4而造成轉移力上升。我們使用聚合酶連鎖反應分析微小核糖核酸-21在不同黑色素細胞癌與人類角質細胞表現量，發現微小核糖核酸-21表現量與黑色素細胞癌惡性度成正相關。進一步用西方墨點法去分析PTEN和PDCD4蛋白表現量，發現PTEN及PDCD4表現量與微小核糖核酸-21表現量在黑色素細胞癌中沒有呈現負相關。用免疫組織化學染色去比較痣與轉移之黑色素細胞癌組織的PDCD4表現量，發現有些癌組織反而比正常的痣的黑色素細胞表現量高。而PTEN在黑色素細胞癌組織表現並沒有全部被抑制。綜合實驗的結果，微小核糖核酸-21表現量與黑色素細胞癌惡性度成正相關，但是其調控黑色素癌轉移的方式也許是透過其他分子機轉而非調降PTEN和PDCD4。

關鍵字

黑色素細胞癌 ； 微小核糖核酸-21

並列摘要

Melanoma is a highly metastatic cancer. Its malignant progression is regulated by the altered gene expression. Studies have found that the loss of tumor suppressors, PTEN (phosphatase and tensin homology) and PDCD4 (programmed cell death 4) attributes to metastasis in many cancer cases, including melanoma. Additionally, many cancer studies reported that mircoRNA-21 over-expressed suppresses PTEN and PDCD4 in melanoma. However, it is unclear in melanoma, whether tumor metastasis is caused by microRNA-21 suppressing PTEN and PDCD4. This report evaluated this hypothesis. We studied the expressions of microRNA-21, PTEN, and PDCD4 in human keratinocyte cells and malignant melanoma cells. The results of reverse transcription-polymerase chain reaction (RT-PCR) assays showed that the levels of microRNA-21 were correlated to the malignancy of melanoma cells. Nevertheless, the results of Western blotting and RT-PCR revealed that the expression of PTEN and PDCD4 did not show a reverse-correlation with the levels of microRNA-21 in melanoma cells. Comparing the expression of PDCD4 in nevus cells with metastatic melanoma tissues, the immunohistochemical stain showed some metastatic melanoma tissues expressing stronger PDCD4 than nevus cells. Meanwhile, some melanoma tissues still showed positive stains of PTEN. These results indicated that microRNA-21expression is correlated in melanoma malignancy, but microRNA-21 may regulate metastasis of melanoma through other mechanism rather than through down-regulating PTEN and PDCD4.

並列關鍵字

microRNA-21 ； melanoma

參考文獻

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