Mir-145過低表現是上泌尿道上皮癌之不良預後因子
柯宏龍1,2,4、林慧惠2,4、李威明1,2,4,6、黃俊農1,2,4、李經家1,2,4,5、張玲麗1,3、葉信志1,2,4,5、吳文正1,2,4,5
高雄醫學大學 醫學研究所1 泌尿學科2 微生物學科3
高雄醫學大學附設醫院泌尿科4、大同醫院泌尿科5、部立屏東醫院泌尿科6
Downregulation of mir-145 predicts a worse outcome in upper tract urothelial carcinomas
Hung-Lung Kea,b,d , Hui-Hui Linb,d , Wei-Ming Lia,b,d,f ,Chun-Nung Huanga,b,d ,Ching-Chia Li a,b,d,e, Lin-Li Changa,c , Hsin-Chih Yeha,b,d,e ,Wen-Jeng Wua,b,d,e
aGraduate Institute of Medicine , bDepartment of Urology , cDepartment of Microbiology , College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan dDepartment of Urology, Kaohsiung Medical University Hospital, eDepartment of Urology, Kaohsiung Municipal Ta-Tung Hospital , Kaohsiung Medical University, Kaohsiung, Taiwan, fPingtung Hospital , Department of Health, Executive Yuan, Pingtung , Taiwan
Purpose:
MicroRNAs (miRNAs) represent a class of small non‑coding RNAs regulating gene expression by inducing the degradation of RNA or interfering with translation. Aberrant miRNA expression has been described in several types of cancer in humans. By our pre-set miR array data, we identified miR-145 as the most significant tumor suppressor mir in urothelial carcinoma (UC). However, the expression of miR-145 in UC of the upper urinary tract (UTUC) has not been investigated. This study is conducted to evaluate the outcome predictive value of miR-145 expression in UTUC.
Materials and Methods:
Using a miRNA array (Applied Biosystems) that included 667 human miRNAs and mammalian RNU6B, we compare the differentially expressed miRNAs between BFTC909 cell line and paired UTUC samples. The miR-145 expression levels from 65 UTUC tissues and the paired adjacent noncancerous tissues were investigated by Real-Time Reverse Transcriptase PCR assay. In addition, the functional consequences of miR145 transfection in BFTC909 cells were studied in vitro by MTT, wound healing, cell migration, cell invasion assays.
Results:
In 65 paired tissues, we found that mir-145 expression was significantly decreased in UTUC tissues than in paired adjacent noncancerous tissues. Decreased mir-145 expression was associated with worse recurrence-free and cancer-specific survival. In cell line experiments, we demonstrated that mir145 can inhibit cell proliferation, migration and invasion in BFTC909 cell line after transfection of miR145 mimics.
Conclusion:
Our findings imply that decreased miR-145 expression is a potential biomarker to predict clinical outcome of UTUC patients. Further study is necessary to identify the molecular mechanisms of miR-145 involved in the cancerous processes of UTUC.