{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:58Z","timestamp":1787028538890,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T00:00:00Z","timestamp":1717113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Greek Universities","award":["2022-050-0502-52198"],"award-info":[{"award-number":["2022-050-0502-52198"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in multiple myeloma (MM) pathogenesis by regulating gene expression. This study evaluated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide\u2013dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both correlated with the depth of response and mir-16 with sustained response to LD treatment. Ratios of both miR-16 and miR-21 expression levels (prior to LD treatment\/diagnosis) below two predicted a shorter time to response (p = 0.027) and a longer time to next treatment (p = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels correlated with disease variables and treatment outcomes.<\/jats:p>","DOI":"10.3390\/ijms25116065","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:35:32Z","timestamp":1717137332000},"page":"6065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Circulating miR-16 and miR-21 Levels in Multiple Myeloma: Prognostic Significance of Survival and Response to Lenalidomide Treatment"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1599-5509","authenticated-orcid":false,"given":"Annita-Ioanna","family":"Gkioka","sequence":"first","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9861-7166","authenticated-orcid":false,"given":"Maria","family":"Tsota","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 17676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3284-3710","authenticated-orcid":false,"given":"Aspasia","family":"Koudouna","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Gkiokas","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina-Aggeliki","family":"Mitropoulou","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 17676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini","family":"Palaiokrassa","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 17676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Alexandropoulos","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mavra","family":"Papadatou-Gigante","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Bartzi","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomais-Marina","family":"Tryfou","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros P.","family":"Sfikakis","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7798-6221","authenticated-orcid":false,"given":"George V.","family":"Dedoussis","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 17676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Kyrtsonis","sequence":"additional","affiliation":[{"name":"Hematology Section, First Department of Propaedeutic Internal Medicine, Laikon Hospital, National and Kapodistrian University of Athens\u2019 Medical School, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ajh.24402","article-title":"Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management","volume":"91","author":"Rajkumar","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1182\/blood.2019004309","article-title":"Risk factors in multiple myeloma: Is it time for a revision?","volume":"137","author":"Corre","year":"2021","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1001\/jama.2022.0003","article-title":"Diagnosis and Management of Multiple Myeloma: A Review","volume":"327","author":"Cowan","year":"2022","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2147\/TACG.S7456","article-title":"Genetic and molecular mechanisms in multiple myeloma: A route to better understand disease pathogenesis and heterogeneity","volume":"3","author":"Kyrtsonis","year":"2010","journal-title":"Appl. Clin. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrclinonc.2011.76","article-title":"MicroRNAs in body fluids--the mix of hormones and biomarkers","volume":"8","author":"Cortez","year":"2011","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1182\/blood-2016-09-742296","article-title":"Prognostic role of circulating exosomal miRNAs in multiple myeloma","volume":"129","author":"Manier","year":"2017","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cbpa.2019.01.024","article-title":"The roles of microRNAs in epigenetic regulation","volume":"51","author":"Yao","year":"2019","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1038\/leu.2014.155","article-title":"Circulating miRNA markers show promise as new prognosticators for multiple myeloma","volume":"28","author":"Rocci","year":"2014","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chakrabortty, A., Patton, D.J., Smith, B.F., and Agarwal, P. (2023). miRNAs: Potential as Biomarkers and Therapeutic Targets for Cancer. Genes, 14.","DOI":"10.20944\/preprints202306.0045.v1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/ijc.32894","article-title":"Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study","volume":"147","author":"Casabonne","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1182\/blood.V106.11.1554.1554","article-title":"MicroRNA Expression Analysis in Multiple Myeloma","volume":"106","author":"Masri","year":"2005","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s12032-014-0094-5","article-title":"MicroRNA-21 and multiple myeloma: Small molecule and big function","volume":"31","author":"Ma","year":"2014","journal-title":"Med. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dubaj, M., Bigosi\u0144ski, K., Dembowska, A., Mlak, R., Szudy-Szczyrek, A., Ma\u0142ecka-Massalska, T., and Homa-Mlak, I. (2024). Role of Non-Coding RNAs in Diagnosis, Prediction and Prognosis of Multiple Myeloma. Cancers, 16.","DOI":"10.3390\/cancers16051033"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/ddr.21257","article-title":"The Role of miR-21 in Cancer","volume":"76","author":"Pfeffer","year":"2015","journal-title":"Drug Dev. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up(\u2020)","volume":"32","author":"Dimopoulos","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"60723","DOI":"10.18632\/oncotarget.11032","article-title":"Role of micro-RNAs in drug resistance of multiple myeloma","volume":"7","author":"Abdi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_17","first-page":"4001","article-title":"The diagnostic and prognostic value of plasma microRNA-125b-5p in patients with multiple myeloma","volume":"16","author":"Jiang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"38270","DOI":"10.18632\/oncotarget.5681","article-title":"MicroRNA-15a\/16-1 cluster located at chromosome 13q14 is down-regulated but displays different expression pattern and prognostic significance in multiple myeloma","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.jmoldx.2015.06.006","article-title":"Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression","volume":"17","author":"Wang","year":"2015","journal-title":"J. Mol. Diagn."},{"key":"ref_20","first-page":"471","article-title":"Circulating Serum MicroRNA as Diagnostic Biomarkers for Multiple Myeloma","volume":"25","author":"Xu","year":"2017","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rhim, J., Baek, W., Seo, Y., and Kim, J.H. (2022). From Molecular Mechanisms to Therapeutics: Understanding MicroRNA-21 in Cancer. Cells, 11.","DOI":"10.3390\/cells11182791"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.3109\/10428194.2011.591004","article-title":"Myeloma cell adhesion to bone marrow stromal cells confers drug resistance by microRNA-21 up-regulation","volume":"52","author":"Wang","year":"2011","journal-title":"Leuk Lymphoma"},{"key":"ref_23","first-page":"1490","article-title":"Clinical Study of miRNAs Derived from Serum Exosomes in Multiple Myeloma","volume":"30","author":"Zhou","year":"2022","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Moura, S.R., Abreu, H., Cunha, C., Ribeiro-Machado, C., Oliveira, C., Barbosa, M.A., Marques, H., and Almeida, M.I. (2021). Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions. Cancers, 13.","DOI":"10.3390\/cancers13215258"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Robak, P., Dr\u00f3\u017cd\u017c, I., Jarych, D., Mikulski, D., W\u0119g\u0142owska, E., Siemieniuk-Ry\u015b, M., Misiewicz, M., Stawiski, K., Fendler, W., and Szemraj, J. (2020). The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients. Cancers, 12.","DOI":"10.3390\/cancers12092569"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1756-8722-4-37","article-title":"Suppressing miRNA-15a\/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells","volume":"4","author":"Hao","year":"2011","journal-title":"J. Hematol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, J.H., Zhou, W.W., Liu, B.X., Man, D.L., Yang, Z.D., Liu, F.R., and Shang, H. (2016). Expression and significance of miR-21 in multiple myeloma patients. Genet. Mol. Res., 15.","DOI":"10.4238\/gmr.15016892"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Xu, Q., Hou, Y.X., Langlais, P., Erickson, P., Zhu, J., Shi, C.X., Luo, M., Zhu, Y., Xu, Y., and Mandarino, L.J. (2016). Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2331-0"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e456","DOI":"10.3324\/haematol.2017.168070","article-title":"Circulating microRNA expressions can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory\/relapsed multiple myeloma","volume":"102","author":"Jung","year":"2017","journal-title":"Haematologica"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1038\/leu.2016.147","article-title":"Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents","volume":"30","author":"Majithia","year":"2016","journal-title":"Leukemia"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/6065\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:51:40Z","timestamp":1760107900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/11\/6065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,31]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["ijms25116065"],"URL":"https:\/\/doi.org\/10.3390\/ijms25116065","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,31]]}}}