NDP067: Extraperitoneal laparoscopic repair of huge inguinoscrotal bladder hernia: A case report and literature review
Small Non-coding MicroRNAs (miRNAs) Target Hepatoma-Derived Growth Factor (HDGF) as a Novel Therapeutic Strategy for Urothelial Carcinoma
小型非編碼核糖核酸靶向肝癌衍生生長因子(HDGF)作為尿路上皮癌治療新策略
孔美蘭1,5、葉碧雯2,3,4、李威明2,3、李經家2,3、吳文正2,3,4,5*
高雄榮總教學研究部1,5，高雄醫學大學泌尿學科2，高雄醫學大學附設醫院泌尿科7，高雄醫學大學再生醫學與細胞治療中心4，國立中山大學醫學科學技術研究所5
Mei-Lang Kung1, 5, Bi-Wen Yeh2, 3, 4, Wei-Ming Li2,3, Ching-Chia Li2,3, and Wen-Jeng Wu2, 3, 4, 5*
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung1; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung2; Department of Urology, KMU Hospital, Kaohsiung3; Regenerative Medicine and Cell Therapy Research Center, KMU, Kaohsiung4; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan5
Purposes:
Previous studies demonstrated that targeting the hepatoma-derived growth factor (HDGF) using non-coding microRNAs significantly decreased HDGF-mediated cell proliferation, invasion, and tumorigenesis. However, the HDGF-associated non-coding microRNAs expression profiles and their roles on tumorigenesis in urothelial carcinoma are still obscured.
Materials and Methods:
We first analyzed hdgf expression profiles in bladder urothelial carcinoma (BLCA) and the Kaplan-Meier survival analysis between normal and control tissues using a TCGA dataset. Next, we collected all the potential miRNA candidates involved in HDGF expression in BLCA by using TCGA microRNA comparison system. We identified five miRNA candidates in UC cell lines such as T24, RT4, BFTC905, J82 and BFTC905. Subsequently, we selected the most efficacy HDGF-targeted miRNA candidates to identify their effects on cell viability, colony formation, invasion assay, and EMT-related signaling in urothelial carcinoma (UC) cell lines.
Results:
By using TCGA database, our result suggested that hdgf gene is highly expression in BLCA as compared to many cancer types. We found that hdgf is highly expression in BLCA tissues rather than normal tissue. Moreover, a significant poor survival was found in 402 bladder urothelial carcinoma patients who shown a higher hdgf expression level. Five miRNA candidates: miR139-5p, miR195-5p, miR497-5p, miR148-3p, and miR-6838-5p were selected and further validated their effects on HDGF expression and cellular biofunctions. Our results shown that all five miRNA candidates were downregulated in high HDGF expressed UC cell lines, such as BFTC905 and BFTC909. Further analysis revealed that overexpression of miR195-5p and miR-6838-5p significantly downregulated cell proliferation in BFTC905 cells.
Conclusions:
Upregulation of HDGF is found in BLCA patients and highly correlated with patient’s survival. In this study, our results demonstrated that downregulation of five HDGF-specific miRNAs: miR139-5p, miR195-5p, miR497-5p, miR148-3p, and miR-6838-5p are significantly associated with higher HDGF expression in UC cell lines. Among that, overexpression of miR195-5p and miR-6838-5p showed dramatically inhibit cell proliferation on BFTC905 cells. Further bio-functional effects of HDGF-specific miRNAs on UC cell lines will be validated in future works.