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Research Article

tRF-20-S998LO9D inhibits endometrial carcinoma by upregulating SESN2

    Tianye Qian‡

    Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China

    ‡Authors contributed equally

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    ,
    Xinnian Yu‡

    Department of Internal Medicine, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China

    ‡Authors contributed equally

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    ,
    Andi Xu‡

    Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China

    ‡Authors contributed equally

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    ,
    Huixin Li

    Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity & Child Health Care Hospital, Nanjing, 210004, China

    ,
    Wei Chen

    Department of Head & Neck Surgery, The Affiliated Cancer Hospital of Nanjing, Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China

    &
    Shanliang Zhong

    *Author for correspondence: Tel.: +86 25 8328 3335;

    E-mail Address: slzhong@njmu.edu.cn

    Center of Clinical Laboratory Science, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210009, China

    Published Online:https://doi.org/10.2217/epi-2022-0349

    Aim: To explore the roles of transfer RNA-derived small RNAs (tsRNAs) in endometrial carcinoma (EC). Materials & methods: tsRNA profiles for EC from TCGA were analyzed. The functions and mechanisms of tsRNA were explored using in vitro experiments. Results: 173 dysregulated tsRNAs were identified. After validating in EC tissues and serumal exosome samples from EC patients, a downregulated tsRNA in both EC tissues and serumal exosomes (i.e., tRF-20-S998LO9D) was observed. Exosomal tRF-20-S998LO9D had an area under the curve of 0.768. tRF-20-S998LO9D overexpression inhibited proliferation, migration and invasion and promoted apoptosis of EC cells and tRF-20-S998LO9D knockdown further confirmed its effects. Further analyses showed that tRF-20-S998LO9D upregulated SESN2 in protein levels. Conclusion: tRF-20-S998LO9D inhibits EC cells by upregulating SESN2.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    Reference

    • 1. Raglan O, Kalliala I, Markozannes G et al. Risk factors for endometrial cancer: an umbrella review of the literature. Int. J. Cancer 145(7), 1719–1730 (2019).
    • 2. Lu KH, Broaddus RR. Endometrial cancer. N. Engl. J. Med. 383(21), 2053–2064 (2020).
    • 3. Njoku K, Abiola J, Russell J, Crosbie EJ. Endometrial cancer prevention in high-risk women. Best Pract. Res. Clin. Obstet. Gynaecol. 65, 66–78 (2020).
    • 4. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68(6), 394–424 (2018).
    • 5. Sundar S, Balega J, Crosbie E et al. BGCS uterine cancer guidelines: recommendations for practice. Eur. J. Obstet. Gynecol. Reprod. Biol. 213, 71–97 (2017).
    • 6. Colombo N, Creutzberg C, Amant F et al. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer: diagnosis, treatment and follow-up. Ann. Oncol. 27(1), 16–41 (2016).
    • 7. Concin N, Matias-Guiu X, Vergote I et al. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int. J. Gynecol. Cancer 31(1), 12–39 (2021). •• Introduced guidelines for the management of patients with endometrial carcinoma.
    • 8. Raffone A, Travaglino A, Raimondo D et al. Prognostic value of myometrial invasion and TCGA groups of endometrial carcinoma. Gynecol. Oncol. 162(2), 401–406 (2021).
    • 9. Talhouk A, Mcconechy MK, Leung S et al. Confirmation of ProMisE: a simple, genomics-based clinical classifier for endometrial cancer. Cancer 123(5), 802–813 (2017).
    • 10. Mcalpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J. Pathol. 244(5), 538–549 (2018).
    • 11. Zhang L, Yu D. Exosomes in cancer development, metastasis, and immunity. Biochim. Biophys. Acta Rev. Cancer 1871(2), 455–468 (2019).
    • 12. Mashouri L, Yousefi H, Aref AR, Ahadi AM, Molaei F, Alahari SK. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol. Cancer 18(1), 75 (2019). • Summarized findings about exosomes.
    • 13. Wang J, Zhang Q, Wang D et al. Microenvironment-induced TIMP2 loss by cancer-secreted exosomal miR-4443 promotes liver metastasis of breast cancer. J. Cell. Physiol. 235(7–8), 5722–5735 (2020).
    • 14. Wang J, Zhang Q, Zhou S et al. Circular RNA expression in exosomes derived from breast cancer cells and patients. Epigenomics 11(4), 411–421 (2019).
    • 15. Zhong S, Chen X, Wang D et al. MicroRNA expression profiles of drug-resistance breast cancer cells and their exosomes. Oncotarget 7(15), 19601–19609 (2016).
    • 16. Zhu L, Li J, Gong Y et al. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis. Mol. Cancer 18(1), 74 (2019). •• Explored transfer RNA-derived small RNAs (tsRNAs) in exosomes.
    • 17. Wang J, Ma G, Ge H et al. Circulating tRNA-derived small RNAs (tsRNAs) signature for the diagnosis and prognosis of breast cancer. NPJ Breast Cancer 7(1), 4 (2021).
    • 18. Jin F, Yang L, Wang W et al. A novel class of tsRNA signatures as biomarkers for diagnosis and prognosis of pancreatic cancer. Mol. Cancer 20(1), 95 (2021).
    • 19. Wang T, Cao L, He S et al. Small RNA sequencing reveals a novel tsRNA-06018 playing an important role during adipogenic differentiation of hMSCs. J. Cell Mol. Med. 24(21), 12736–12749 (2020).
    • 20. Li J, Zhu L, Cheng J, Peng Y. Transfer RNA-derived small RNA: a rising star in oncology. Semin. Cancer Biol. doi: 10.1016/j.semcancer.2021.05.024 (2021). •• Summarized the current understanding of the roles of tsRNAs in cancer
    • 21. Fang S, He T, Jiang J, Li Y, Chen P. Osteogenic effect of tsRNA-10277-loaded exosome derived from bone mesenchymal stem cells on steroid-induced osteonecrosis of the femoral head. Drug Des. Devel. Ther. 14, 4579–4591 (2020).
    • 22. Jia Y, Tan W, Zhou Y. Transfer RNA-derived small RNAs: potential applications as novel biomarkers for disease diagnosis and prognosis. Ann. Transl. Med. 8(17), 1092 (2020).
    • 23. Pliatsika V, Loher P, Telonis AG, Rigoutsos I. MINTbase: a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments. Bioinformatics 32(16), 2481–2489 (2016).
    • 24. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15(12), 550 (2014).
    • 25. Zhong S, Lin Z, Chen H, Mao L, Feng J, Zhou S. The m(6)A-related gene signature for predicting the prognosis of breast cancer. PeerJ 9, e11561 (2021).
    • 26. Xie Y, Yao L, Yu X, Ruan Y, Li Z, Guo J. Action mechanisms and research methods of tRNA-derived small RNAs. Signal Transduct. Target Ther. 5(1), 109 (2020).
    • 27. Kumar P, Anaya J, Mudunuri SB, 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. 12, 78 (2014).
    • 28. Kuscu C, Kumar P, Kiran M, Su Z, Malik A, Dutta A. tRNA fragments (tRFs) guide ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 24(8), 1093–1105 (2018).
    • 29. Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic Acids Res. 48(D1), D127–D131 (2020).
    • 30. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS. MicroRNA targets in Drosophila. Genome Biol. 5(1), R1 (2003).
    • 31. Kruger J, Rehmsmeier M. RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res. 34, W451–454 (2006).
    • 32. Shannon P, Markiel A, Ozier O et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13(11), 2498–2504 (2003).
    • 33. Zhou SY, Chen W, Yang SJ et al. Circular RNA circVAPA regulates breast cancer cell migration and invasion via sponging miR-130a-5p. Epigenomics 12(4), 303–317 (2020).
    • 34. Li K, Lin Y, Luo Y et al. A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study. Mol. Cancer 21(1), 21 (2022). •• Explored saliva-derived exosomal small RNAs.
    • 35. Poller W, Dimmeler S, Heymans S et al. Non-coding RNAs in cardiovascular diseases: diagnostic and therapeutic perspectives. Eur. Heart J. 39(29), 2704–2716 (2018).
    • 36. He C, Zheng S, Luo Y, Wang B. Exosome theranostics: biology and translational medicine. Theranostics 8(1), 237–255 (2018).
    • 37. Wang C, Li Z, Liu Y, Yuan L. Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets. Theranostics 11(8), 3996–4010 (2021).
    • 38. Shen Y, Yu X, Zhu L, Li T, Yan Z, Guo J. Transfer RNA-derived fragments and tRNA halves: biogenesis, biological functions and their roles in diseases. J. Mol. Med. 96(11), 1167–1176 (2018). • Summarized biogenesis and biological functions of tsRNAs.
    • 39. Goodarzi H, Liu X, Nguyen H, Zhang S, Fish L, Tavazoie S. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell 161(4), 790–802 (2015).
    • 40. Wen JT, Huang ZH, Li QH, Chen X, Qin HL, Zhao Y. Research progress on the tsRNA classification, function, and application in gynecological malignant tumors. Cell Death Discov. 7(1), 388 (2021).
    • 41. Cordani M, Sánchez-Álvarez M, Strippoli R, Bazhin A, Donadelli M. Sestrins at the interface of ROS control and autophagy regulation in health and disease. Oxid. Med. Cellul. Longev. 2019, 1283075 (2019).
    • 42. Wang BJ, Wang S, Xiao M et al. Regulatory mechanisms of Sesn2 and its role in multi-organ diseases. Pharmacol. Res. 164, 105331 (2021).
    • 43. Kim H, Yin K, Falcon DM, Xue X. The interaction of hemin and sestrin2 modulates oxidative stress and colon tumor growth. Toxicol. Appl. Pharmacol. 374, 77–85 (2019).
    • 44. Pham DV, Raut PK, Pandit M et al. Globular adiponectin inhibits breast cancer cell growth through modulation of inflammasome activation: critical role of sestrin2 and AMPK signaling. Cancers (Basel) 12(3), 613 (2020).
    • 45. Wei JL, Fang M, Fu ZX et al. Sestrin 2 suppresses cells proliferation through AMPK/mTORC1 pathway activation in colorectal cancer. Oncotarget 8(30), 49318–49328 (2017).
    • 46. Hua X, Xu J, Deng X et al. New compound ChlA-F induces autophagy-dependent anti-cancer effect via upregulating sestrin-2 in human bladder cancer. Cancer Lett. 436, 38–51 (2018).
    • 47. Jeong S, Kim DY, Kang SH et al. Docosahexaenoic acid enhances oxaliplatin-induced autophagic cell death via the ER stress/Sesn2 pathway in colorectal cancer. Cancers (Basel) 11(7), 982 (2019).
    • 48. Shin J, Bae J, Park S et al. mTOR-dependent role of sestrin2 in regulating tumor progression of human endometrial cancer. Cancers (Basel) 12(9), 2515 (2020).
    • 49. Troisi J, Mollo A, Lombardi M et al. The metabolomic approach for the screening of endometrial cancer: validation from a large cohort of women scheduled for gynecological surgery. Biomolecules 12(9), 1229 (2022).
    • 50. Raffone A, Troisi J, Boccia D et al. Metabolomics in endometrial cancer diagnosis: a systematic review. Acta Obstet. Gynecol. Scand. 99(9), 1135–1146 (2020). •• Summarized metabolomics in endometrial cancer diagnosis.
    • 51. Xu H, Gong Z, Shen Y, Fang Y, Zhong S. Circular RNA expression in extracellular vesicles isolated from serum of patients with endometrial cancer. Epigenomics 10(2), 187–197 (2018). • Explored circular RNAs in extracellular vesicles.
    • 52. Zhou L, Wang W, Wang F et al. Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma. Mol. Cancer 20(1), 57 (2021).