tRNA‑derived fragment tRF‑Glu49 inhibits cell proliferation, migration and invasion in cervical cancer by targeting FGL1

Wang,Yang; Wang,Yang; Xia,Wenying; Xia,Wenying; Shen,Fangrong; Shen,Fangrong; Zhou,Jinhua; Zhou,Jinhua; Gu,Yanzheng; Gu,Yanzheng; Chen,Youguo; Chen,Youguo

doi:10.3892/ol.2022.13455

tRNA‑derived fragment tRF‑Glu49 inhibits cell proliferation, migration and invasion in cervical cancer by targeting FGL1

Authors:
- Yang Wang
- Wenying Xia
- Fangrong Shen
- Jinhua Zhou
- Yanzheng Gu
- Youguo Chen
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Affiliations: Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital Group Suqian Hospital and The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, Jiangsu 223800, P.R. China, Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China
Published online on: August 9, 2022 https://doi.org/10.3892/ol.2022.13455
Article Number: 334
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A transfer RNA (tRNA)‑derived fragment (tRF) was found to be a new possible biological marker and target in carcinoma therapy. However, the effect exerted by tRFs on cervical carcinoma remains unclear. In the present study, the potential tumor suppressor gene tRF‑Glu49 was identified in cervical carcinoma through tRF and tiRNA microarray investigation. A reverse transcription‑quantitative PCR assay then demonstrated that tRF‑Glu49 was downregulated in the cervical carcinoma tissue. Further clinicopathological analysis proved that tRF‑Glu49 was associated with less aggressive clinical features and improved prognosis. Cell Counting Kit‑8 tests, Transwell and Matrigel tests, and xCELLigence system tests revealed that tRF‑Glu49 inhibited cervical cell proliferation, migration and invasion processes. Mechanistic investigation revealed that tRF‑Glu49 directly regulated the oncogene, fibrinogen‑like protein‑1 (FGL1). In general, according to the result achieved in the present study, tRF‑Glu49 can modulate cervical cell proliferation, migration, and invasion processes through the target process for FGL1, and tRF‑Glu49 is likely to be a possible prognostic biological marker in patients with cervical carcinoma.

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1	Shrestha AD, Neupane D, Vedsted P and Kallestrup P: Cervical cancer prevalence, incidence and mortality in low and middle income countries: A systematic review. Asian Pac J Cancer Prev. 19:319–324. 2018.PubMed/NCBI
2	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
3	Crafton SM and Salani R: Beyond chemotherapy: An overview and review of targeted therapy in cervical cancer. Clin Ther. 38:449–458. 2016. View Article : Google Scholar : PubMed/NCBI
4	Kokka F, Bryant A, Brockbank E, Powell M and Oram D: Hysterectomy with radiotherapy or chemotherapy or both for women with locally advanced cervical cancer. Cochrane Database Syst Rev. 7:CD0102602015.PubMed/NCBI
5	de Freitas AC, da Conceição Gomes Leitão M and Coimbra EC: Prospects of molecularly-targeted therapies for cervical cancer treatment. Curr Drug Targets. 16:77–91. 2015. View Article : Google Scholar : PubMed/NCBI
6	Waggoner SE: Cervical cancer. Lancet. 361:2217–2225. 2003. View Article : Google Scholar : PubMed/NCBI
7	Kawaji H, Nakamura M, Takahashi Y, Sandelin A, Katayama S, Fukuda S, Daub CO, Kai C, Kawai J, Yasuda J, et al: Hidden layers of human small RNAs. BMC Genomics. 9:1572008. View Article : Google Scholar : PubMed/NCBI
8	Cole C, Sobala A, Lu C, Thatcher SR, Bowman A, Brown JWS, Green PJ, Barton GJ and Hutvagner G: Filtering of deep sequencing data reveals the existence of abundant dicer-dependent small RNAs derived from tRNAs. RNA. 15:2147–2160. 2009. View Article : Google Scholar : PubMed/NCBI
9	Pekarsky Y, Balatti V, Palamarchuk A, Rizzotto L, Veneziano D, Nigita G, Rassenti LZ, Pass HI, Kipps TJ, Liu CG and Croce CM: Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. Proc Natl Acad Sci USA. 113:5071–5076. 2016. View Article : Google Scholar : PubMed/NCBI
10	Soares AR and Santos M: Discovery and function of transfer RNA-derived fragments and their role in disease. Wiley Interdiscip Rev RNA. 8:doi: 10.1002/wrna.1423. 2017. View Article : Google Scholar : PubMed/NCBI
11	Kumar P, Kuscu C and Dutta A: Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem Sci. 41:679–689. 2016. View Article : Google Scholar : PubMed/NCBI
12	Keam SP and Hutvagner G: tRNA-derived fragments (tRFs): Emerging new roles for an ancient RNA in the regulation of gene expression. Life (Basel). 5:1638–1651. 2015.PubMed/NCBI
13	Huang B, Yang H, Cheng X, Wang D, Fu S, Shen W, Zhang Q, Zhang L, Xue Z, Li Y, et al: tRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Res. 77:3194–3206. 2017. View Article : Google Scholar : PubMed/NCBI
14	Li S, Shi X, Chen M, Xu N, Sun D, Bai R, Chen H, Ding K, Sheng J and Xu Z: Angiogenin promotes colorectal cancer metastasis via tiRNA production. Int J Cancer. 145:1395–1407. 2019. View Article : Google Scholar : PubMed/NCBI
15	Olvedy M, Scaravilli M, Hoogstrate Y, Visakorpi T, Jenster G and Martens-Uzunova ES: A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget. 7:24766–24777. 2016. View Article : Google Scholar : PubMed/NCBI
16	Zhao C, Tolkach Y, Schmidt D, Muders M, Kristiansen G, Müller SC and Ellinger J: tRNA-halves are prognostic biomarkers for patients with prostate cancer. Urol Oncol. 36:503.e501–503.e507. 2018. View Article : Google Scholar : PubMed/NCBI
17	Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L and Tavazoie SF: Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell. 161:790–802. 2015. View Article : Google Scholar : PubMed/NCBI
18	Honda S, Loher P, Shigematsu M, Palazzo JP, Suzuki R, Imoto I, Rigoutsos I and Kirino Y: Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc Natl Acad Sci USA. 112:E3816–E3825. 2015. View Article : Google Scholar : PubMed/NCBI
19	Balatti V, Pekarsky Y and Croce CM: Role of the tRNA-derived small RNAs in cancer: New potential biomarkers and target for therapy. Adv Cancer Res. 135:173–187. 2017. View Article : Google Scholar : PubMed/NCBI
20	Jang K, Ahn H, Sim J, Han H, Abdul R, Paik SS, Chung MS and Jang SJ: Loss of microRNA-200a expression correlates with tumor progression in breast cancer. Transl Res. 163:242–251. 2014. View Article : Google Scholar : PubMed/NCBI
21	Shi J, Zhang Y, Tan D, Zhang X, Yan M, Zhang Y, Franklin R, Shahbazi M, Mackinlay K, Liu S, et al: PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications. Nat Cell Biol. 23:424–436. 2021. View Article : Google Scholar : PubMed/NCBI
22	Cui Y, Huang Y, Wu X, Zheng M, Xia Y, Fu Z, Ge H, Wang S and Xie H: Hypoxia-induced tRNA-derived fragments, novel regulatory factor for doxorubicin resistance in triple-negative breast cancer. J Cell Physiol. 234:8740–8751. 2019. View Article : Google Scholar : PubMed/NCBI
23	Sun C, Yang F, Zhang Y, Chu J, Wang J, Wang Y, Zhang Y, Li J, Li Y, Fan R, et al: tRNA-derived fragments as novel predictive biomarkers for trastuzumab-resistant breast cancer. Cell Physiol Biochem. 49:419–431. 2018. View Article : Google Scholar : PubMed/NCBI
24	Lee YS, Shibata Y, Malhotra A and Dutta A: A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 23:2639–2649. 2009. View Article : Google Scholar : PubMed/NCBI
25	Maute RL, Schneider C, Sumazin P, Holmes A, Califano A, Basso K and Dalla-Favera R: tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci USA. 110:1404–1409. 2013. View Article : Google Scholar : PubMed/NCBI
26	Loss-Morais G, Waterhouse PM and Margis R: Description of plant tRNA-derived RNA fragments (tRFs) associated with argonaute and identification of their putative targets. Biol Direct. 8:62013. View Article : Google Scholar : PubMed/NCBI
27	Kumar P, Anaya J, Mudunuri SB and 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. 12:782014. View Article : Google Scholar : PubMed/NCBI
28	Shigematsu M and Kirino Y: tRNA-derived short non-coding RNA as interacting partners of argonaute proteins. Gene Regul Syst Biol. 9:27–33. 2015.PubMed/NCBI
29	Yee VC, Pratt KP, Cote HC, Trong IL, Chung DW, Davie EW, Stenkamp RE and Teller DC: Crystal structure of a 30 kDa C-terminal fragment from the gamma chain of human fibrinogen. Structure. 5:125–138. 1997. View Article : Google Scholar : PubMed/NCBI
30	Shi AP, Tang XY, Xiong YL, Zheng KF, Liu YJ, Shi XG, Lv Y, Jiang T, Ma N and Zhao JB: Immune checkpoint LAG3 and its ligand FGL1 in cancer. Front Immunol. 12:7850912021. View Article : Google Scholar : PubMed/NCBI
31	Sun C, Gao W, Liu J, Cheng H and Hao J: FGL1 regulates acquired resistance to Gefitinib by inhibiting apoptosis in non-small cell lung cancer. Respir Res. 21:2102020. View Article : Google Scholar : PubMed/NCBI
32	Lv Z, Cui B, Huang X, Feng HY, Wang T, Wang HF, Xuan YD, Li HZ, Ma X, Huang Y and Zhang X: FGL1 as a novel mediator and biomarker of malignant progression in clear cell renal cell carcinoma. Front Oncol. 11:7568432021. View Article : Google Scholar : PubMed/NCBI
33	Qian W, Zhao M, Wang R and Li H: Fibrinogen-like protein 1 (FGL1): The next immune checkpoint target. J Hematol Oncol. 14:1472021. View Article : Google Scholar : PubMed/NCBI
34	Yan Q, Lin HM, Zhu K, Cao Y, Xu XL, Zhou ZY, Xu LB, Liu C and Zhang R: Immune checkpoint FGL1 expression of circulating tumor cells is associated with poor survival in curatively resected hepatocellular carcinoma. Front Oncol. 12:8102692022. View Article : Google Scholar : PubMed/NCBI
35	Wang J, Sanmamed MF, Datar I, Su TT, Ji L, Sun J, Chen L, Chen Y, Zhu G, Yin W, et al: Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell. 176:334–347.e312. 2019. View Article : Google Scholar : PubMed/NCBI