Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Các exosome huyết thanh tuần hoàn i-tRF-AspGTC và tRF-1-SerCGA như các chỉ thị chẩn đoán cho ung thư phổi không phải tế bào nhỏ
Tóm tắt
tRF-RNA—một đại diện của RNA không mã hóa (ncRNA)—là một tiền chất hoặc mảnh của tRNA trưởng thành và đóng vai trò điều hòa quan trọng trong quá trình hình thành và phát triển của ung thư. Hiện tại, có rất ít nghiên cứu về tRF-RNA như một dấu hiệu chẩn đoán trong ung thư, đặc biệt là ung thư phổi không phải tế bào nhỏ (NSCLC) từ exosome huyết thanh. Exosome huyết thanh đã được chiết xuất thành công từ huyết thanh; hình thái vật lý của chúng được ghi lại bằng kính hiển vi điện tử truyền qua (TEM); việc phát hiện kích thước hạt phù hợp đã được thực hiện bằng cách sử dụng qNano; việc gán bề mặt đã được xác minh thông qua phân tích western blotting. Exosome huyết thanh i-tRF-AspGTC và tRF-1-SerCGA đã được chọn thông qua vi mảng gen, và qPCR đã được sử dụng để xác thực tầm quan trọng của chúng ở 242 bệnh nhân và 201 cá nhân khỏe mạnh. Diện tích dưới đường cong (AUC) đã được sử dụng để đánh giá các chỉ số chẩn đoán của ung thư phổi không phải tế bào nhỏ (NSCLC). So với 201 cá nhân khỏe mạnh, i-tRF-AspGTC và tRF-1-SerCGA đã giảm đáng kể ở 242 bệnh nhân NSCLC và 95 bệnh nhân ở giai đoạn đầu. Đối với tRF-AspGTC và tRF-1-SerCGA, tỷ lệ hiệu suất chẩn đoán dự đoán của AUC lần lượt là 0.690 và 0.680, trong khi tỷ lệ hiệu suất chẩn đoán sớm là 0.656 và 0.688, tương ứng. Kết quả của việc chẩn đoán kết hợp với CEA và CYFRA21-1 là 0.928, và hiệu suất chẩn đoán sớm là 0.843, đây là một yếu tố dự đoán sinh học rất cao cho NSCLC. Biểu hiện của các exosome huyết thanh i-tRF-AspGTC và tRF-1-SerCGA đã giảm đáng kể ở bệnh nhân NSCLC. Những exosome này có thể được sử dụng như các chỉ số dự đoán cho chẩn đoán hoặc chẩn đoán sớm ung thư phổi không phải tế bào nhỏ (NSCLC).
Từ khóa
#tRF-RNA #ung thư phổi không phải tế bào nhỏ #exosome huyết thanh #chỉ thị chẩn đoán #qPCR #khám sàng lọcTài liệu tham khảo
Chen P, Liu Y, Wen Y, Zhou C. Non-small cell lung cancer in China. Cancer Commun (Lond). 2022;42:937–70. https://doi.org/10.1002/cac2.12359.
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553:446–54. https://doi.org/10.1038/nature25183.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(2021):209–49. https://doi.org/10.3322/caac.21660.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics. CA Cancer J Clin. 2022;72(2022):7–33. https://doi.org/10.3322/caac.21708.
Gao S, Li N, Wang S, Zhang F, Wei W, Li N, Bi N, Wang Z, He J. Lung cancer in People’s Republic of China. J Thorac Oncol. 2020;15:1567–76. https://doi.org/10.1016/j.jtho.2020.04.028.
Kumar P, Mudunuri SB, Anaya J, Dutta A. tRFdb: a database for transfer RNA fragments. Nucleic Acids Res. 2015;43:D141-145. https://doi.org/10.1093/nar/gku1138.
Lee YS, Shibata Y, Malhotra A, Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009;23:2639–49. https://doi.org/10.1101/gad.1837609.
Losh JS, King AK, Bakelar J, Taylor L, Loomis J, Rosenzweig JA, Johnson SJ, van Hoof A. Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing. Nucleic Acids Res. 2015;43:1848–58. https://doi.org/10.1093/nar/gkv005.
Yu M, Lu B, Zhang J, Ding J, Liu P, Lu Y. tRNA-derived RNA fragments in cancer: current status and future perspectives. J Hematol Oncol. 2020;13:121. https://doi.org/10.1186/s13045-020-00955-6.
Lu S, Wei X, Tao L, Dong D, Hu W, Zhang Q, Tao Y, Yu C, Sun D, Cheng H. A novel tRNA-derived fragment tRF-3022b modulates cell apoptosis and M2 macrophage polarization via binding to cytokines in colorectal cancer. J Hematol Oncol. 2022;15:176. https://doi.org/10.1186/s13045-022-01388-z.
Cui H, Li H, Wu H, Du F, Xie X, Zeng S, Zhang Z, Dong K, Shang L, Jing C, Li L. A novel 3′tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer. Cell Death Dis. 2022;13:471. https://doi.org/10.1038/s41419-022-04930-6.
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. 2018;24:1093–105. https://doi.org/10.1261/rna.066126.118.
Sun C, Fu Z, Wang S, Li J, Li Y, Zhang Y, Yang F, Chu J, Wu H, Huang X, Li W, Yin Y. Roles of tRNA-derived fragments in human cancers. Cancer Lett. 2018;414:16–25. https://doi.org/10.1016/j.canlet.2017.10.031.
Hong W, Xue M, Jiang J, Zhang Y, Gao X. Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC). J Exp Clin Cancer Res. 2020;39:149. https://doi.org/10.1186/s13046-020-01648-1.
Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, Valente N, Shreeniwas R, Sutton MA, Delcayre A, Hsu DH, Le Pecq JB, Lyerly HK. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3:9. https://doi.org/10.1186/1479-5876-3-9.
Zhang C, Wang XY, Zhang P, He TC, Han JH, Zhang R, Lin J, Fan J, Lu L, Zhu WW, Jia HL, Zhang JB, Chen JH. Cancer-derived exosomal HSPC111 promotes colorectal cancer liver metastasis by reprogramming lipid metabolism in cancer-associated fibroblasts. Cell Death Dis. 2022;13:57. https://doi.org/10.1038/s41419-022-04506-4.
Cao W, Dai S, Ruan W, Long T, Zeng Z, Lei S. Pancreatic stellate cell-derived exosomal tRF-19-PNR8YPJZ promotes proliferation and mobility of pancreatic cancer through AXIN2. J Cell Mol Med. 2023. https://doi.org/10.1111/jcmm.17852.
Wang D, Zhao C, Xu F, Zhang A, Jin M, Zhang K, Liu L, Hua Q, Zhao J, Liu J, Yang H, Huang G. Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2. Theranostics. 2021;11:2860–75. https://doi.org/10.7150/thno.51797.
Yang P, Zhang X, Chen S, Tao Y, Ning M, Zhu Y, Liang J, Kong W, Shi B, Li Z, Shen H, Wang Y. A novel serum tsRNA for diagnosis and prediction of nephritis in SLE. Front Immunol. 2021;12:735105. https://doi.org/10.3389/fimmu.2021.735105.
Wang W, Zhu L, Li H, Ren W, Zhuo R, Feng C, He Y, Hu Y, Ye C. Alveolar macrophage-derived exosomal tRF-22-8BWS7K092 activates Hippo signaling pathway to induce ferroptosis in acute lung injury. Int Immunopharmacol. 2022;107:108690. https://doi.org/10.1016/j.intimp.2022.108690.
Zhang Z, Tang Y, Song X, Xie L, Zhao S, Song X. Tumor-derived exosomal miRNAs as diagnostic biomarkers in non-small cell lung cancer. Front Oncol. 2020;10:560025. https://doi.org/10.3389/fonc.2020.560025.
Zhang ZJ, Song XG, Xie L, Wang KY, Tang YY, Yu M, Feng XD, Song XR. Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer. Exp Biol Med (Maywood). 2020;245:1428–36. https://doi.org/10.1177/1535370220945987.
Mathieu M, Névo N, Jouve M, Valenzuela JI, Maurin M, Verweij FJ, Palmulli R, Lankar D, Dingli F, Loew D, Rubinstein E, Boncompain G, Perez F, Théry C. Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nat Commun. 2021;12:4389. https://doi.org/10.1038/s41467-021-24384-2.
Nasim F, Sabath BF, Eapen GA. Lung cancer. Med Clin North Am. 2019;103:463–73. https://doi.org/10.1016/j.mcna.2018.12.006.
Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS. Lung cancer. Lancet. 2021;398:535–54. https://doi.org/10.1016/s0140-6736(21)00312-3.
Alexander M, Kim SY, Cheng H. Update 2020: management of non-small cell lung cancer. Lung. 2020;198:897–907. https://doi.org/10.1007/s00408-020-00407-5.
Zhang Q, Liu Z, Han X, Li Y, Xia T, Zhu Y, Li Z, Wang L, Hao L, Hu F, Cao Y, Han C, Zhu Z. Circulatory exosomal tRF-Glu-CTC-005 and tRF-Gly-GCC-002 serve as predictive factors of successful microdissection testicular sperm extraction in patients with nonobstructive azoospermia. Fertil Steril. 2022;117:512–21. https://doi.org/10.1016/j.fertnstert.2021.11.010.
Zhao L, Wang H, Fu J, Wu X, Liang XY, Liu XY, Wu X, Cao LL, Xu ZY, Dong M. Microfluidic-based exosome isolation and highly sensitive aptamer exosome membrane protein detection for lung cancer diagnosis. Biosens Bioelectron. 2022;214:114487. https://doi.org/10.1016/j.bios.2022.114487.
Dai J, Su Y, Zhong S, Cong L, Liu B, Yang J, Tao Y, He Z, Chen C, Jiang Y. Exosomes: key players in cancer and potential therapeutic strategy. Signal Transduct Target Ther. 2020;5:145. https://doi.org/10.1038/s41392-020-00261-0.
Mohammadi M, Zargartalebi H, Salahandish R, Aburashed R, Wey Yong K, Sanati-Nezhad A. Emerging technologies and commercial products in exosome-based cancer diagnosis and prognosis, Biosens Bioelectron. 2021;183:113176. https://doi.org/10.1016/j.bios.2021.113176.
Wu Y, Yang X, Jiang G, Zhang H, Ge L, Chen F, Li J, Liu H, Wang H. 5′-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis. Genome Med. 2021;13:20. https://doi.org/10.1186/s13073-021-00833-x.
Weng Q, Wang Y, Xie Y, Yu X, Zhang S, Ge J, Li Z, Ye G, Guo J. Extracellular vesicles-associated tRNA-derived fragments (tRFs): biogenesis, biological functions, and their role as potential biomarkers in human diseases. J Mol Med (Berl). 2022;100:679–95. https://doi.org/10.1007/s00109-022-02189-0.
Salunkhe S, Dheeraj M, Basak D, Chitkara A. Mittal, Surface functionalization of exosomes for target-specific delivery and in vivo imaging & tracking: strategies and significance. J Control Release. 2020;326:599–614. https://doi.org/10.1016/j.jconrel.2020.07.042.
Wang C, Li Z, Liu Y, Yuan L. Exosomes in atherosclerosis: performers, bystanders, biomarkers, and therapeutic targets. Theranostics. 2021;11:3996–4010. https://doi.org/10.7150/thno.56035.
Jiang L, Dong H, Cao H, Ji X, Luan S, Liu J. Exosomes in pathogenesis, diagnosis, and treatment of Alzheimer’s disease. Med Sci Monit. 2019;25:3329–35. https://doi.org/10.12659/msm.914027.
Chu X, He C, Sang B, Yang C, Yin C, Ji M, Qian A, Tian Y. Transfer RNAs-derived small RNAs and their application potential in multiple diseases. Front Cell Dev Biol. 2022;10: 954431. https://doi.org/10.3389/fcell.2022.954431.
Yu X, Song X, Xie Y, Zhang S, Guo J. Establishment of an absolute quantitative method to detect a plasma tRNA-derived fragment and its application in the non-invasive diagnosis of gastric cancer. Int J Mol Sci. 2022;24. https://doi.org/10.3390/ijms24010322.
Brokāne A, Bajo-Santos C, Zayakin P, Belovs A, Jansons J, Lietuvietis V, Martens-Uzunova ES, Jenster GW, Linē A. Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles. Front Mol Biosci. 2023;10:1279854. https://doi.org/10.3389/fmolb.2023.1279854.
Jiang Q, Ma Y, Zhao Y, Yao MD, Zhu Y, Zhang QY, Yan B. tRNA-derived fragment tRF-1001: A novel anti-angiogenic factor in pathological ocular angiogenesis. Mol Ther Nucleic Acids. 2022;30:407–20. https://doi.org/10.1016/j.omtn.2022.10.016.
Zhang Y, Gu X, Qin X, Huang Y, Ju S. Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer. Mol Med. 2022;28:63. https://doi.org/10.1186/s10020-022-00491-8.
Han Y, Peng Y, Liu S, Wang X, Cai C, Guo C, Chen Y, Gao L, Huang Q, He M, Shen E, Long J, Yu J, Shen H, Zeng S. tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner. J Exp Clin Cancer Res. 2022;41:32. https://doi.org/10.1186/s13046-021-02190-4.
Zhang Y, Bi Z, Dong X, Yu M, Wang K, Song X, Xie L, Song X. tRNA-derived fragments: tRF-Gly-CCC-046, tRF-Tyr-GTA-010 and tRF-Pro-TGG-001 as novel diagnostic biomarkers for breast cancer, Thorac. Cancer. 2021;12:2314–23. https://doi.org/10.1111/1759-7714.14072.
Kazimierczyk M, Wojnicka M, Biała E, Żydowicz-Machtel P, Imiołczyk B, Ostrowski T, Kurzyńska-Kokorniak A, Wrzesinski J. Characteristics of transfer RNA-derived fragments expressed during human renal cell development: the role of dicer in tRF biogenesis. Int J Mol Sci. 2022;23. https://doi.org/10.3390/ijms23073644.
Park J, Ahn SH, Shin MG, Kim HK, Chang S. tRNA-derived small RNAs: novel epigenetic regulators. Cancers (Basel). 2020;12. https://doi.org/10.3390/cancers12102773.
Pan L, Huang X, Liu ZX, Ye Y, Li R, Zhang J, Wu G, Bai R, Zhuang L, Wei L, Li M, Zheng Y, Su J, Deng J, Deng S, Zeng L, Zhang S, Wu C, Che X, Wang C, Chen R, Lin D, Zheng J. Inflammatory cytokine-regulated tRNA-derived fragment tRF-21 suppresses pancreatic ductal adenocarcinoma progression. J Clin Invest. 2021;131. https://doi.org/10.1172/jci148130.
Magee R, Rigoutsos I. On the expanding roles of tRNA fragments in modulating cell behavior. Nucleic Acids Res. 2020;48:9433–48. https://doi.org/10.1093/nar/gkaa657.
Hu Y, Cai A, Xu J, Feng W, Wu A, Liu R, Cai W, Chen L, Wang F. An emerging role of the 5′ termini of mature tRNAs in human diseases: Current situation and prospects. Biochim Biophys Acta Mol Basis Dis. 2022;1868:166314. https://doi.org/10.1016/j.bbadis.2021.166314.
Panoutsopoulou K, Magkou P, Dreyer T, Dorn J, Obermayr E, Mahner S, van Gorp T, Braicu I, Magdolen V, Zeillinger R, Avgeris M, Scorilas A. tRNA-derived small RNA 3′U-tRF(ValCAC) promotes tumour migration and early progression in ovarian cancer. Eur J Cancer. 2023;180:134–45. https://doi.org/10.1016/j.ejca.2022.11.033.
Pekarsky Y, Balatti V, Croce CM. tRNA-derived fragments (tRFs) in cancer. J Cell Commun Signal. 2023;17:47–54. https://doi.org/10.1007/s12079-022-00690-2.
