miR‐17‐3p promotes the proliferation of multiple myeloma cells by downregulating P21 expression through LMLN inhibition

• Published in: International journal of cancer Vol. 148; no. 12; pp. 3071 - 3085
• Main Authors: Xiang, Pu, Yeung, Yiu To, Wang, Jiheng, Wu, Qiong, Du, Ruijuan, Huang, Chuntian, Jia, Xuechao, Gao, Yunfeng, Zhi, Yafei, Guo, Fangqin, Wei, Huifang, Zhang, Dandan, Liu, Yuzhang, Liu, Lina, Liang, Lijie, Wang, Juan, Song, Yongping, Liu, Kangdong, Fang, Baijun
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.06.2021; Wiley Subscription Services, Inc
• Subjects: Apoptosis; Benign monoclonal gammopathy; Bone marrow; Cancer; Cell cycle; Cell growth; Cell proliferation; Chromosome 3; Cyclin-dependent kinase inhibitor p21; Hematology; Leukocytes (mononuclear); LMLN; M protein; Malignancy; Medical research; miR‐17‐3p; Molecular Cancer Biology; Multiple myeloma; p21; plasma biomarker; Prognosis; Tumor cell lines; LMLN; multiple myeloma; plasma biomarker; miR-17-3p; p21
• DOI: 10.1002/ijc.33528
• ISSN: 0020-7136; 1097-0215

Multiple myeloma (MM), a hematological malignancy, has a poor prognosis and requires an invasive procedure. Reports have implicated miRNAs in the diagnosis, treatment and prognosis of hematological malignancies. In our study, we evaluated the expression profiles of miR‐17‐3p in plasma and bone marrow mononuclear cells of monoclonal gammopathy of undetermined significance (MGUS) and MM patients and healthy subjects. The results showed that the plasma and mononuclear cell expression levels of miR‐17‐3p in MM patients were higher than those in MGUS patients and normal controls. In addition, the expression of miR‐17‐3p was positively correlated with diagnostic indexes, such as marrow plasma cell abundance and serum M protein level, and positively correlated with the International Staging System stage of the disease. Receiver operating characteristic curve analysis suggested that miR‐17‐3p might be a diagnostic index of MM. Moreover, miR‐17‐3p regulated cell proliferation, apoptosis and the cell cycle through P21 in MM cell lines and promoted MM tumor growth in vivo. Furthermore, we predicted and verified LMLN as a functional downstream target gene of miR‐17‐3p. Negatively regulated by miR‐17‐3p, LMLN inhibits MM cell growth, exerting a tumor suppressive function through P21. Taken together, our data identify miR‐17‐3p as a promising diagnostic biomarker for MM in the clinic and unveil a new miR‐17‐3p‐LMLN‐P21 axis in MM progression. What's new MicroRNAs have shown potential in the diagnosis, treatment, and prognosis of hematological malignancies. Here, the authors found that miR‐17‐3p is highly expressed in the plasma and bone marrow cells of multiple myeloma patients. miR‐17‐3p expression is positively correlated with diagnostic indexes as well as the stage of disease. Moreover, miR‐17‐3p exerts an oncogenic role by regulating the proliferation, apoptosis, cell cycle, and colony formation of multiple myeloma cells by targeting LMLN and regulating P21. Altogether, the results identify miR‐17‐3p as a promising diagnostic biomarker and unveil the role of the miR‐17‐3p‐LMLN‐P21 axis in multiple myeloid progression.