TRNA-Derived Fragment Alleviates Cisplatin-Induced Apoptosis in Prostate Cancer Cells

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2021 Jan 7

PMID 33406670

Citations 23

Authors

Changwon Yang

Minkyeong Lee

Gwonhwa Song

Whasun Lim

Affiliations

Soon will be listed here.

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 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.

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References

Qin D, Li H, Xie H . Ultrasound‑targeted microbubble destruction‑mediated miR‑205 enhances cisplatin cytotoxicity in prostate cancer cells. Mol Med Rep. 2018; 18(3):3242-3250. PMC: 6102709. DOI: 10.3892/mmr.2018.9316. View

Thompson D, Lu C, Green P, Parker R . tRNA cleavage is a conserved response to oxidative stress in eukaryotes. RNA. 2008; 14(10):2095-103. PMC: 2553748. DOI: 10.1261/rna.1232808. View

Su L, Xin H, Liu Y, Zhang J, Xin H, Su X . Anticancer bioactive peptide (ACBP) inhibits gastric cancer cells by upregulating growth arrest and DNA damage-inducible gene 45A (GADD45A). Tumour Biol. 2014; 35(10):10051-6. DOI: 10.1007/s13277-014-2272-7. View

Moriyama-Gonda N, Shiina H, Terashima M, Satoh K, Igawa M . Rationale and clinical implication of combined chemotherapy with cisplatin and oestrogen in prostate cancer: primary evidence based on methylation analysis of oestrogen receptor-alpha. BJU Int. 2007; 101(4):485-91. DOI: 10.1111/j.1464-410X.2007.07256.x. View

Arencibia J, Del Rio M, Bonnin A, Lopes R, Lemoine N, Lopez-Barahona M . Doxazosin induces apoptosis in LNCaP prostate cancer cell line through DNA binding and DNA-dependent protein kinase down-regulation. Int J Oncol. 2005; 27(6):1617-23. View

Falconi M, Giangrossi M, Elexpuru Zabaleta M, Wang J, Gambini V, Tilio M . A novel 3'-tRNA-derived fragment acts as a tumor suppressor in breast cancer by targeting nucleolin. FASEB J. 2019; 33(12):13228-13240. DOI: 10.1096/fj.201900382RR. View

Lee Y, Shibata Y, Malhotra A, Dutta A . A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009; 23(22):2639-49. PMC: 2779758. DOI: 10.1101/gad.1837609. View

Kanwal R, Plaga A, Liu X, Shukla G, Gupta S . MicroRNAs in prostate cancer: Functional role as biomarkers. Cancer Lett. 2017; 407:9-20. DOI: 10.1016/j.canlet.2017.08.011. View

Dasari S, Tchounwou P . Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014; 740:364-78. PMC: 4146684. DOI: 10.1016/j.ejphar.2014.07.025. View

10.

Chiang K, Tsui K, Chung L, Yeh C, Feng T, Chen W . Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways. Sci Rep. 2014; 4:5511. PMC: 4076686. DOI: 10.1038/srep05511. View

11.

Goodarzi H, Liu X, Nguyen H, Zhang S, Fish L, Tavazoie S . Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell. 2015; 161(4):790-802. PMC: 4457382. DOI: 10.1016/j.cell.2015.02.053. View

12.

Olvedy M, Scaravilli M, Hoogstrate Y, Visakorpi T, Jenster G, Martens-Uzunova E . A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget. 2016; 7(17):24766-77. PMC: 5029740. DOI: 10.18632/oncotarget.8293. View

13.

Zhu L, Ge J, Li T, Shen Y, Guo J . tRNA-derived fragments and tRNA halves: The new players in cancers. Cancer Lett. 2019; 452:31-37. DOI: 10.1016/j.canlet.2019.03.012. View

14.

Barabas K, Milner R, Lurie D, Adin C . Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol. 2009; 6(1):1-18. DOI: 10.1111/j.1476-5829.2007.00142.x. View

15.

Lee S, Kim Y . Phosphorylation of eIF2α attenuates statin-induced apoptosis by inhibiting the stabilization and translocation of p53 to the mitochondria. Int J Oncol. 2013; 42(3):810-6. PMC: 3597453. DOI: 10.3892/ijo.2013.1792. View

16.

Kumar P, Anaya J, Mudunuri S, Dutta A . Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets. BMC Biol. 2014; 12:78. PMC: 4203973. DOI: 10.1186/s12915-014-0078-0. View

17.

Magee R, Telonis A, Loher P, Londin E, Rigoutsos I . Profiles of miRNA Isoforms and tRNA Fragments in Prostate Cancer. Sci Rep. 2018; 8(1):5314. PMC: 5871839. DOI: 10.1038/s41598-018-22488-2. View

18.

Wade C, Kyprianou N . Profiling Prostate Cancer Therapeutic Resistance. Int J Mol Sci. 2018; 19(3). PMC: 5877765. DOI: 10.3390/ijms19030904. View

19.

Rodriguez M, Bajo-Santos C, Hessvik N, Lorenz S, Fromm B, Berge V . Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes. Mol Cancer. 2017; 16(1):156. PMC: 5629793. DOI: 10.1186/s12943-017-0726-4. View

20.

Jin L, Zhu C, Qin X . Expression profile of tRNA-derived fragments in pancreatic cancer. Oncol Lett. 2019; 18(3):3104-3114. PMC: 6676665. DOI: 10.3892/ol.2019.10601. View