Circulating tumour cells differentially express upregulated cancer biomarkers “lncRNAs and miRNAs” compared to bone marrow biopsy samples in multiple myeloma patients

Yıl 2024, Cilt: 41 Sayı: 2, 351 - 360, 19.05.2024

Gizem Ayna Duran

Öz

Easy-to-apply liquid biopsy technique and detection of differentially expressed miRNA/lncRNAs (DEGs) may be more beneficial in multiple myeloma (MM) compared to bone marrow (BM) biopsy. We compared the gene expression levels of circulating tumor cells and BM cells in MM patients and showed differentially upregulated circulating tumor cell-derived miRNAs and lncRNAs. DEGs and related biological pathways were identified by using the R-LIMMA package, ShinyGO 0.77, and LncSEA2.0 tools. Three hundred nine lncRNAs/16 miRNAs were detected as differentially upregulated in MM patients’ circulating tumour cells. Among them, miRNAs (mainly has-miR-103a) and lncRNAs (MEG3, NEAT1, PCAT1) were detected, and only a few miRNAs and lncRNAs were related to MM in a limited number of studies. Drugs that interact with these lncRNAs were also identified. The fact that miRNAs/lncRNAs related to MM are also detected in tumor circulating cells indicates that a technically easier liquid biopsy may verify and even replace BM biopsy.

Anahtar Kelimeler

Circulating tumour cells, multiple myeloma, DEGs, miRNA, lncRNAs

Etik Beyan

No ethical statement is required since publicly available data are used.

Destekleyen Kurum

There is no supporting institution and funding.

Proje Numarası

None

Teşekkür

None

Kaynakça

• Shaji K. Kumar, Vincent Rajkumar, Robert A. Kyle1, et al. (2017) Multiple myeloma. Nat Rev Dis Primers 3, 17046. https://doi.org/10.1038/nrdp.2017.46
• Claudio Cerchione, Saad Z. Usmani, A. Keith Stewart, et al. Gene Expression Profiling in Multiple Myeloma: Redefining the Paradigm of Risk-Adapted Treatment Front Oncol . 2022 Feb 8;12:820768. doi: 10.3389/fonc.2022.820768.
• Andrew J., Cowan, Damian J. Green, Mary Kwok, et al. (2022) Diagnosis and Management of Multiple Myeloma JAMA. 327(5):464-477. doi:10.1001/jama.2022.0003
• Cinzia Federico, Antonio Sacco, Angelo Belotti, et al. (2019) Circulating microRNAs and Their Role in Multiple Myeloma Non-coding RNA 5, 37; doi:10.3390/ncrna5020037
• S Vincent Rajkumar, Meletios A Dimopoulos, Antonio Palumbo, et al. (2014) International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol., 15, 538–548
• Anaïs Schavgoulidze, Titouan Cazaubiel, Aurore Perrot. (2021) Multiple Myeloma: Heterogeneous in Every Way Cancers (Basel). 2021 Mar 13;13(6):1285. doi: 10.3390/cancers13061285.
• Alessandro Allegra, Gabriella Cancemi, Giuseppe Mirabile, et al. (2022) Circulating Tumour Cells, Cell Free DNA and Tumour-Educated Platelets as Reliable Prognostic and Management Biomarkers for the Liquid Biopsy in Multiple Myeloma Cancers 14, 4136. https://doi.org/10.3390/cancers14174136
• Irene M Ghobrial (2012) Myeloma as a model for the process of metastasis: implications for therapy Blood. 120(1):20-30. doi: 10.1182/blood-2012-01-379024.
• Juan-Jose Garcés, Michal Simicek, Marco Vicari, et al. (2020) Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination Leukemia 34:589–603 https://doi.org/10.1038/s41375-019-0588-4
• Sanoja-Flores L, Flores-Montero J, Garcés JJ, et al. (2018) Next generation flow for minimallyinvasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC). Blood Cancer J. 8:117. doi: 10.1038/s41408-018-0153-9
• Gonsalves WI, Rajkumar SV, Dispenzieri A, et al. (2017) Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression. Leukemia. 31:130–5. doi:10.1038/leu.2016.205
• Mehrdad Hashemi, Sophie Mousavian Roshanzamir, Mahshid Deldar Abad Paskeh, et al. (2023) Non-coding RNAs and exosomal ncRNAs in multiple myeloma: An emphasis on molecular pathways European Journal of Pharmacology 941:(15), doi: https://doi.org/10.1016/j.ejphar.2022.175380
• Dan Chen, Xinhong Yang, Min Liu, et al. (2021) Roles of miRNA dysregulation in the pathogenesis of multiple myeloma Cancer Gene Therapy 28:1256–1268 https://doi.org/10.1038/s41417-020-00291-4
• Ilaria Saltarella, Benedetta Apollonio, Aurelia Lamanuzzi, et al. (2022) The Landscape of lncRNAs in Multiple Myeloma: Implications in the “Hallmarks of Cancer”, Clinical Perspectives and Therapeutic Opportunities Cancers 14, 1963. https://doi.org/10.3390/cancers14081963
• van Duin M, Kuiper R, Hofste op Bruinink D, et al. (2022) Identification of High-Risk Multiple Myeloma With a Plasma Cell Leukemia-Like Transcriptomic Profile. J Clin Oncol 20;40(27):3132-3150. PMID: 35357885
• Shi L, Campbell G, Jones WD, et al. (2010) The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models. Nat Biotechnol 28(8):827-38. PMID: 20676074
• YongMing Yang, ZhiFeng Wu, Ming Wang, et al. (2022) MicroRNA-429 Regulates Invasion and Migration of Multiple Myeloma Cells via Bmi1/AKT Pathway Journal of Biomaterials and Tissue Engineering 12(12):2419-2426 doi:10.1166/jbt.2022.3196
• Fakhredin Saba, Masoud Soleimani, Saeid Abroun. (2018) New role of hypoxia in pathophysiology of multiple myeloma through miR-210 EXCLI J . 4;17:647-662. doi: 10.17179/excli2018-1109.
• Chen F, Wang X, Fu S, et al. (2020) Circular RNA circ-CDYL sponges miR-1180 to elevate yesassociated protein in multiple myeloma. Experimental Biology and Medicine 245(11):925-932.
• Peng Xiao, Wenliang Liu, Hui Zhou. (2021) miR-429 promotes the proliferation of non-small cell lung cancer cells via targeting DLC-1 Oncol Lett. 22(1):545. doi: 10.3892/ol.2021.12806 19
• Taoqiong Li, Li Lin, Qin Liu, et al. (2021) Exosomal transfer of miR-429 confers chemoresistance in epithelial ovarian cancer Am J Cancer Res. 2021 11(5):2124-2141. PMCID: PMC8167704
• Claudia Cava, Chiara Novello, Cristina Martelli, et al. (2020) Theranostic application of miR-429 in HER2+ breast cancer Theranostics. 10(1):50-61. doi:10.7150/thno.36274. eCollection 2020. 21
• Senlin Zhao, Hongcheng Sun, Weiliang Jiang, et al. (2017) miR-4775 promotes colorectal cancer invasion and metastasis via the Smad7/TGFβ-mediated epithelial to mesenchymal transition Mol Cancer. 16(1):12. doi: 10.1186/s12943-017-0585-z. 22
• Jiangeng Yang, Yuchen Liu, Anbang He, et al. (2017) Hsa-miR-429 promotes bladder cancer cell proliferation via inhibiting CDKN2B Oncotarget. 8(40):68721-68729. doi: 10.18632/oncotarget.19878. 23
• Kaiyou Fu, Yanrui Li, Jianyuan Song, et al. (2021) Identification of a MicroRNA Signature Associated with Lymph Node Metastasis in Endometrial Endometrioid Cancer Front. Genet., 12:650102. doi: 10.3389/fgene.2021.650102.
• Jiajun Shou, Shixin Gu, Wentao Gu. (2015) Identification of dysregulated miRNAs and their regulatory signature in glioma patients using the partial least squares method Exp Ther Med. 2015 Jan;9(1):167-171. doi: 10.3892/etm.2014.2041.
• Harriet E Gee, Carme Camps, Francesca M Buffa, et al. (2010) hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer Cancer 116(9):2148-58. doi: 10.1002/cncr.25009.
• Junqiang Fan, Guanxin Xu, Zhibo Chang, et al. (2020) miR-210 transferred by lung cancer cell-derived exosomes may act as proangiogenic factor in cancer-associated fibroblasts by modulating JAK2/STAT3 pathway Clin Sci (Lond). 134(7):807-825. doi: 10.1042/CS20200039.
• Zhongqing Li, Lanting Liu, Chenxing Du, et al. (2020) Therapeutic effects of oligo-single-stranded DNA mimicking of hsa-miR-15a-5p on multiple myeloma Cancer Gene Ther. 27(12):869-877. doi: 10.1038/s41417-020-0161-3.
• Zhipeng Li, Zeyu Zhu, Yanjun Wang, et al. (2021) hsa‑miR‑15a‑5p inhibits colon cell carcinoma via targeting CCND1 Mol Med Rep. 24(4):735. doi: 10.3892/mmr.2021.12375.
• Amriti R. Lulla, Michael J. Slifker, Yan Zhou, et al. (2017) miR-6883 Family miRNAs Target CDK4/6 to Induce G1 Phase Cell-Cycle Arrest in Colon Cancer Cells Cancer Res; 77(24) doi: 10.1158/0008-5472.CAN-17-1767 30
• Zihan Zhou, Xianguo Zhou, Yanji Jiang, et al. (2020) Clinical significance of miR-1180-3p in hepatocellular carcinoma: a study based on bioinformatics analysis and RT-qPCR validation Sci Rep. 2020 10(1):11573. doi: 10.1038/s41598-020-68450-z. 31
• Yu-Ting Hua, Wen-Xiu Xu, Hui Li, et al. (2021) Emerging roles of MiR-133a in human cancers Journal of Cancer J Cancer. 12(1):198-206. doi: 10.7150/jca.48769.
• A.S. Pal, M. Bains, A. Agredo, et al. (2021) Identification of microRNAs that promote erlotinib resistance in non-small cell lung cancer Biochem Pharmacol. 189:114154. doi: 10.1016/j.bcp.2020.114154.
• Xuan Huang, Mingjie Huang, Lingbao Kong, et al. (2015) miR-372 suppresses tumour proliferation and invasion by targeting IGF2BP1 in renal cell carcinoma Cell Prolif. 48(5):593-9. doi: 10.1111/cpr.12207.
• Harshini Sriram, Twinkle Khanka, Sanghamitra Gawai, et al. (2022) Serum microRNA Signature Predicting Poor Therapeutic Response to Bortezomib-Based Therapy and Clinical Outcome in Newly Diagnosed Multiple Myeloma: A Result of miRNA Profiling By Deep Sequencing Blood 4292–4293. https://doi.org/10.1182/blood-2022-168598
• Yiming Zhang, Ran Kang, Wenrong Liu, et al. (2017) Identification and Analysis of P53-Mediated Competing Endogenous RNA Network in Human Hepatocellular Carcinoma Int J Biol Sci. 13(9):1213-1221. doi: 10.7150/ijbs.21502.
• Bo Li, Xianyi Liu, Guogang Wu, et al. (2021) MicroRNA-934 facilitates cell proliferation, migration, invasion and angiogenesis in colorectal cancer by targeting B-cell translocation gene 2, Bioengineered, 12:2, 9507-9519, DOI: 10.1080/21655979.2021.1996505
• C. M. Guo, S. Q. Liu, M. Z. Sun. (2020) miR-429 as biomarker for diagnosis, treatment and prognosis of cancers and its potential action mechanisms: A systematic literature review Neoplasma 67(2): 215–228 doi:10.4149/neo_2019_190401N282
• Aldo M. Roccaro, Antonio Sacco, Brian Thompson, et al. (2009) MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood 113, 6669–6680. doi: https://doi.org/10.1182/blood-2009-01-198408
• Chun-Yan Sun, Xiao-Mei She, You Qin, et al. (2013) miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF. Carcinogenesis 34, 426–435. doi: 10.1093/carcin/bgs333
• Wenzhuo Zhuang, Xueping Ge, Sijun Yang, et al. (2015) Upregulation of lncRNA MEG3 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells From Multiple Myeloma Patients By Targeting BMP4 Transcription Stem Cells. 33(6):1985-97. doi: 10.1002/stem.1989.
• Xiaoyan Zang, Jing Wang, Yuan Xia, et al. (2022) LncRNA MEG3 promotes the sensitivity of bortezomib by inhibiting autophagy in multiple myeloma Leuk Res. 123:106967. doi: 10.1016/j.leukres.2022.106967.
• Xuxing Shen, Hua Bai, Huayuan Zhu, et al. (2018) Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma Cell Physiol Biochem 49(1):87-100. doi: 10.1159/000492846.
• Yin Gao, Peng Fang, Wen-Jin Li, et al. (2020) LncRNA NEAT1 sponges miR-214 to regulate M2 macrophage polarization by regulation of B7-H3 in multiple myeloma Molecular Immunology 117(20-28)
• Yilan Wu, Han Wang. (2018) LncRNA NEAT1 promotes dexamethasone resistance in multiple myeloma by targeting miR-193a/MCL1 pathway JBiochemMolToxicol. 32(1). https://doi.org/10.1002/jbt.22008
• Haifeng Yu, Shuailing Peng, Xi Chen, et al. (2020) Long non-coding RNA NEAT1 serves as a novel biomarker for treatment response and survival profiles via microRNA-125a in multiple myeloma J Clin Lab Anal. 34:e23399 https://doi.org/10.1002/jcla.23399
• Elisa Taiana, Vanessa Favasuli, Domenica Ronchetti, et al. (2020) Long non-coding RNA NEAT1 targeting impairs the DNA repair machinery and triggers anti-tumor activity in multiple myeloma Leukemia. 34(1):234-244. doi: 10.1038/s41375-019-0542-5.
• Xianjuan Shen, Yan Zhang, Xian Wu, et al. (2017) Upregulated lncRNA-PCAT1 is closely related to clinical diagnosis of multiple myeloma as a predictive biomarker in serum Cancer Biomark. 18(3):257-263. doi: 10.3233/CBM-160158.
• Peng Zhao, Xiaohong Zhao. (2021) Baseline lncRNA PCAT1 high expression and its longitude increment during induction therapy predict worse prognosis in multiple myeloma patients J Clin Lab Anal. 35(11):e23924. doi: 10.1002/jcla.23924.