TRNA-derived Fragments As Novel Potential Biomarkers for Relapsed/refractory Multiple Myeloma

Overview

Journal BMC Bioinformatics

Publisher Biomed Central

Specialty Biology

Date 2021 May 11

PMID 33971811

Citations 6

Authors

Cong Xu

Ting Liang

Fangrong Zhang

Jing Liu

Yunfeng Fu

Affiliations

Soon will be listed here.

Abstract

Background: tRNA-derived fragments have been reported to be key regulatory factors in human tumors. However, their roles in the progression of multiple myeloma remain unknown.

Results: This study employed RNA-sequencing to explore the expression profiles of tRFs/tiRNAs in new diagnosed MM and relapsed/refractory MM samples. The expression of selected tRFs/tiRNAs were further validated in clinical specimens and myeloma cell lines by qPCR. Bioinformatic analysis was performed to predict their roles in multiple myeloma progression.We identified 10 upregulated tRFs/tiRNAs and 16 downregulated tRFs/tiRNAs. GO enrichment and KEGG pathway analysis were performed to analyse the functions of 1 significantly up-regulated and 1 significantly down-regulated tRNA-derived fragments. tRFs/tiRNAs may be involved in MM progression and drug-resistance.

Conclusion: tRFs/tiRNAs were dysregulated and could be potential biomarkers for relapsed/refractory MM.

Citing Articles

tRNA-Derived Small RNAs: A Novel Regulatory Small Noncoding RNA in Renal Diseases.

Li D, Xie X, Yin N, Wu X, Yi B, Zhang H Kidney Dis (Basel). 2024; 10(1):1-11.

PMID: 38322624 PMC: 10843216. DOI: 10.1159/000533811.

Maternal Serum tRNA-Derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease.

Lu E, Wu L, Chen B, Xu S, Fu Z, Wu Y J Cardiovasc Dev Dis. 2023; 10(2).

PMID: 36826574 PMC: 9968204. DOI: 10.3390/jcdd10020078.

Emerging roles of tRNA-derived fragments in cancer.

Fu M, Gu J, Wang M, Zhang J, Chen Y, Jiang P Mol Cancer. 2023; 22(1):30.

PMID: 36782290 PMC: 9926655. DOI: 10.1186/s12943-023-01739-5.

A 5`-tRNA Derived Fragment NamedtiRNA-Val-CAC-001 Works as a Suppressor in Gastric Cancer.

Zheng J, Li C, Zhu Z, Yang F, Wang X, Jiang P Cancer Manag Res. 2022; 14:2323-2337.

PMID: 35958946 PMC: 9359412. DOI: 10.2147/CMAR.S363629.

tRNA Derivatives in Multiple Myeloma: Investigation of the Potential Value of a tRNA-Derived Molecular Signature.

Karousi P, Papanota A, Artemaki P, Liacos C, Patseas D, Mavrianou-Koutsoukou N Biomedicines. 2021; 9(12).

PMID: 34944627 PMC: 8698603. DOI: 10.3390/biomedicines9121811.

References

Chng W, Gonzalez-Paz N, Price-Troska T, Jacobus S, Rajkumar S, Oken M . Clinical and biological significance of RAS mutations in multiple myeloma. Leukemia. 2008; 22(12):2280-4. PMC: 3864109. DOI: 10.1038/leu.2008.142. View

Xia J, He Y, Meng B, Chen S, Zhang J, Wu X . NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma. Mol Oncol. 2020; 14(4):763-778. PMC: 7138399. DOI: 10.1002/1878-0261.12641. View

Tian F, Zhan Y, Zhu W, Li J, Tang M, Chen X . MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2. Int J Mol Med. 2018; 43(2):1058-1066. DOI: 10.3892/ijmm.2018.4019. View

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

Yang X, Liu M, Li M, Zhang S, Hiju H, Sun J . Epigenetic modulations of noncoding RNA: a novel dimension of Cancer biology. Mol Cancer. 2020; 19(1):64. PMC: 7092482. DOI: 10.1186/s12943-020-01159-9. View

Maute R, Schneider C, Sumazin P, Holmes A, Califano A, Basso K . tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A. 2013; 110(4):1404-9. PMC: 3557069. DOI: 10.1073/pnas.1206761110. View

Yuan X, Ma R, Yang S, Jiang L, Wang Z, Zhu Z . miR-520g and miR-520h overcome bortezomib resistance in multiple myeloma via suppressing APE1. Cell Cycle. 2019; 18(14):1660-1669. PMC: 6619958. DOI: 10.1080/15384101.2019.1632138. View

Gonzalez-Hormazabal P, Musleh M, Bustamante M, Stambuk J, Pisano R, Valladares H . Polymorphisms in RAS/RAF/MEK/ERK Pathway Are Associated with Gastric Cancer. Genes (Basel). 2019; 10(1). PMC: 6356706. DOI: 10.3390/genes10010020. View

Guzzi N, Bellodi C . Novel insights into the emerging roles of tRNA-derived fragments in mammalian development. RNA Biol. 2020; 17(8):1214-1222. PMC: 7549657. DOI: 10.1080/15476286.2020.1732694. View

10.

Gao M, Li C, Xiao H, Dong H, Jiang S, Fu Y . hsa_circ_0007841: A Novel Potential Biomarker and Drug Resistance for Multiple Myeloma. Front Oncol. 2019; 9:1261. PMC: 6877741. DOI: 10.3389/fonc.2019.01261. View

11.

Iyer M, Niknafs Y, Malik R, Singhal U, Sahu A, Hosono Y . The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015; 47(3):199-208. PMC: 4417758. DOI: 10.1038/ng.3192. View

12.

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(1):121. PMC: 7487644. DOI: 10.1186/s13045-020-00955-6. View

13.

Anderson P, Ivanov P . tRNA fragments in human health and disease. FEBS Lett. 2014; 588(23):4297-304. PMC: 4339185. DOI: 10.1016/j.febslet.2014.09.001. View

14.

Veneziano D, Tomasello L, Balatti V, Palamarchuk A, Rassenti L, Kipps T . Dysregulation of different classes of tRNA fragments in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2019; 116(48):24252-24258. PMC: 6883801. DOI: 10.1073/pnas.1913695116. View

15.

Fricker R, Brogli R, Luidalepp H, Wyss L, Fasnacht M, Joss O . A tRNA half modulates translation as stress response in Trypanosoma brucei. Nat Commun. 2019; 10(1):118. PMC: 6328589. DOI: 10.1038/s41467-018-07949-6. View

16.

Kim H, Fuchs G, Wang S, Wei W, Zhang Y, Park H . A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature. 2017; 552(7683):57-62. PMC: 6066594. DOI: 10.1038/nature25005. View

17.

Cui Y, Huang Y, Wu X, Zheng M, Xia Y, Fu Z . Hypoxia-induced tRNA-derived fragments, novel regulatory factor for doxorubicin resistance in triple-negative breast cancer. J Cell Physiol. 2018; 234(6):8740-8751. DOI: 10.1002/jcp.27533. View

18.

Chan L, Zhou L, Ng K, Wong T, Lee T, Sharma R . PRMT6 Regulates RAS/RAF Binding and MEK/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation. Cell Rep. 2018; 25(3):690-701.e8. DOI: 10.1016/j.celrep.2018.09.053. View

19.

Lamanuzzi A, Saltarella I, Desantis V, Frassanito M, Leone P, Racanelli V . Inhibition of mTOR complex 2 restrains tumor angiogenesis in multiple myeloma. Oncotarget. 2018; 9(29):20563-20577. PMC: 5945497. DOI: 10.18632/oncotarget.25003. View

20.

Ivanov P, Emara M, Villen J, Gygi S, Anderson P . Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell. 2011; 43(4):613-23. PMC: 3160621. DOI: 10.1016/j.molcel.2011.06.022. View