Abstract
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 tRNALys, 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 GADD45A, 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.
Highlights
Prostate cancer is the third leading cause of cancer-related death among men worldwide [1]
The results revealed thatPathway the tRNA-derived fragments (tRFs)-315 in Prostate Cancer Cells mimic alone inhibited the apoptosis of LNCaP (9.5 ± 0.3%, p < 0.01) and DU145 (8.5 ± 1.1%,cells we investigated inhibition of tRF-315 affectsincrease the expression of proteins p < 0.01)
We found that the cisplatin-mediated increase in the expression of BAX was alleviated by siGADD45A in LNCaP (35.1 ± 0.1%, p < 0.05)
Summary
Prostate cancer is the third leading cause of cancer-related death among men worldwide [1]. Platinum-based anticancer drugs, including cisplatin, are used to treat prostate cancer; long-term cisplatin treatment leads to the development of resistance in patients [2]. Cisplatin works by binding to DNA and, in prostate cancer, it inhibits cell growth and induces apoptosis in both a P53-dependent and -independent manner [3,4]. Several pieces of research have shown that different types of non-coding RNAs (ncRNAs) are involved in the progression of prostate cancer and can be used to predict the prognosis for chemotherapy [5,6]. Among ncRNAs, small non-coding RNAs (sncRNAs), which are shorter than 40 nucleotides in length and include micro RNAs (miRNAs), contribute to genetic regulation through complementary binding to DNA and are associated with the development of several human diseases, including cancer [7]. SncRNAs regulate the sensitivity of cancer cells to anticancer agents [9,10,11]
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