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|Title: ||泌尿道上皮癌相關的miRNAs在膀胱癌之研究;Study of urothelial carcinoma-related miRNAs in bladder cancer|
|Authors: ||方培倫;Fang, Pei-Luen|
|Keywords: ||泌尿道上皮癌;膀胱癌;miRNA;urothelial carcinoma;bladder cancer|
|Issue Date: ||2019-09-03 14:54:05 (UTC+8)|
|Abstract: ||在泌尿系統中，泌尿道上皮癌（Urothelial carcinoma, UC）是一種常見的惡性疾病，由病變的泌尿上皮所衍生而成，過去又稱作移行上皮細胞癌，通常伴隨著較差的預後，且有高達90%的膀胱癌（Bladder cancer, BC）病患都是泌尿道上皮癌患者。一般來說，泌尿道上皮癌發生在男性身上的機率較女性高，在年長者中機率較年輕人高。在台灣的病患中，泌尿道上皮癌也是最常見的泌尿道腫瘤，然而泌尿道上皮癌卻很難在早期被發現。經統計發現，慢性腎臟病人患有泌尿道上皮癌的機率是一般人的七倍；洗腎病人患有泌尿道上皮癌的機率是一般人的兩、三百倍。|
再者，我們為了調查候選miRNA對BC的影響，因此對兩株膀胱癌細胞株 (RT4, J82) 進行轉染，發現當候選miRNA過度表達時，J82和RT4細胞的生長速率沒有明顯下降，但在過度表達miR-19a-5p和miR-155-5p時，J82細胞群體數量顯著減少。另外，我們也觀察到當miR-150-5p過度表達時，會抑制J82細胞的遷移爬行能力；當miR-19a-5p、miR-30a-5p、miR-155-5p過度表達時，會抑制J82細胞的侵襲能力。這些結果說明候選miRNA可能會參與抑癌作用，但miR-19b-1-5p並不會抑制腫瘤的細胞增生、爬行與侵襲。
;Bladder cancer (BC) is a common malignant disease with poor prognosis in urinary system, which occurs in men more often than women and usually affects older adults. About 90% of bladder cancer is urothelial carcinoma (UC) which is known as transitional cell carcinoma (TCC) previously. UC is the most common urinary tract tumor in Taiwan patients. However, it is hard to be diagnosed at early stage. In addition, it has been found that the risk of developing UC in chronic kidney disease (CKD) patients is seven times higher than in normal people and the risk of developing UC in hemodialysis (HD) patients is 200-300 times higher than in normal people.
Our previous data showed that the expression of several miRNAs in urine and plasma were significant different between CKD patients and CKD patients with UC, or between HD patients and HD patients with UC. We chose these miRNAs as our candidate miRNAs to study their roles in BC.
Firstly, we analyzed the data of candidate miRNAs from ArrayExpress database and predicted the targets from four websites. Then, we obtained the survival rate curves of patients. The results showed that only the expression of miR-19b-1-5p significantly regulate survival of BC patients. Patients with high expression of miR-19b-1-5p had significantly longer overall survival than those with low expression. miR-19b-1-5p might act as a tumor suppressor. The expression of four miRNAs target genes significantly regulate survival of BC patients. Most interestingly, miR-19b-1-5p appeared to target EDN1 gene to have an impact on overall survival in BC patients.
Furthermore, we transfected negative control (NC) or candidate miRNA mimics in two BC cells (J82 and RT4) in order to know the function of these miRNAs in BC. We found that overexpression of candidate miRNAs could not significantly inhibit cell proliferation in J82 and RT4 cells. But, overexpression of miR-19a-5p and miR-155-5p could significantly decrease cell colonies in J82 cells. We also observed that overexpression of miR-150-5p could inhibit migration in J82 cells and overexpression of miR-19a-5p, miR-30a-5p, and miR-155-5p could inhibit invasion in J82 cells. The data indicated that these miRNAs might be associated with BC anti-carcinogenesis, but overexpression of miR-19b-1-5p did not inhibit cell proliferation, colony formation, migration and invasion.
Finally, because of different results from survival curves and functional tests, we investigated the expression of candidate miRNAs in patients’ serum and cells through GEO database and RT-qPCR analysis. We found that almost of candidate miRNAs have higher expression in BC. The data might indicate that UC-related miRNAs were involved in BC carcinogenesis, and we will further investigate the reasons for different results.
|Appears in Collections:||[系統生物與生物資訊研究所] 博碩士論文|
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