Yang Changwon, Lee Minkyeong, Song Gwonhwa, Lim Whasun
Department of Biotechnology, Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Korea.
Department of Food and Nutrition, College of Science and Technology, Kookmin University, Seoul 02707, Korea.
Pharmaceutics. 2021 Jan 4;13(1):55. doi: 10.3390/pharmaceutics13010055.
Cisplatin is a standard treatment for prostate cancer, which is the third leading cause of cancer-related deaths among men globally. However, patients who have undergone cisplatin can rxperience relapse. tRNA-derived fragments (tRFs) are small non-coding RNAs generated via tRNA cleavage; their physiological activities are linked to the development of human diseases. Specific tRFs, including tRF-315 derived from tRNA, are highly expressed in prostate cancer patients. However, whether tRF-315 regulates prostate cancer cell proliferation or apoptosis is unclear. Herein, we confirmed that tRF-315 expression was higher in prostate cancer cells (LNCaP, DU145, and PC3) than in normal prostate cells. tRF-315 prevented cisplatin-induced apoptosis and alleviated cisplatin-induced mitochondrial dysfunction in LNCaP and DU145 cells. Moreover, transfection of tRF-315 inhibitor increased the expression of apoptotic pathway-related proteins in LNCaP and DU145 cells. Furthermore, tRF-315 targeted the tumor suppressor gene , thus regulating the cell cycle, which was altered by cisplatin in LNCaP and DU145 cells. Thus, tRF-315 protects prostate cancer cells from mitochondrion-dependent apoptosis induced by cisplatin treatment.
顺铂是前列腺癌的标准治疗药物，前列腺癌是全球男性癌症相关死亡的第三大主要原因。然而，接受顺铂治疗的患者可能会复发。tRNA衍生片段（tRFs）是通过tRNA切割产生的小非编码RNA；它们的生理活性与人类疾病的发展有关。特定的tRFs，包括源自tRNA的tRF-315，在前列腺癌患者中高度表达。然而，tRF-315是否调节前列腺癌细胞的增殖或凋亡尚不清楚。在此，我们证实tRF-315在前列腺癌细胞（LNCaP、DU145和PC3）中的表达高于正常前列腺细胞。tRF-315可预防顺铂诱导的LNCaP和DU145细胞凋亡，并减轻顺铂诱导的线粒体功能障碍。此外，转染tRF-315抑制剂可增加LNCaP和DU145细胞中凋亡途径相关蛋白的表达。此外，tRF-315靶向肿瘤抑制基因，从而调节细胞周期，而LNCaP和DU145细胞中的细胞周期因顺铂而改变。因此，tRF-315可保护前列腺癌细胞免受顺铂治疗诱导的线粒体依赖性凋亡。
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