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

被引:19
|
作者
Xiang, Pu [1 ,2 ]
Yeung, Yiu To [3 ]
Wang, Jiheng [4 ,5 ]
Wu, Qiong [3 ,6 ]
Du, Ruijuan [3 ,6 ]
Huang, Chuntian [3 ,6 ]
Jia, Xuechao [3 ,6 ]
Gao, Yunfeng [3 ]
Zhi, Yafei [3 ,6 ]
Guo, Fangqin [6 ]
Wei, Huifang [3 ,6 ]
Zhang, Dandan [3 ]
Liu, Yuzhang [1 ,2 ]
Liu, Lina [1 ,2 ]
Liang, Lijie [1 ,2 ]
Wang, Juan [1 ,2 ]
Song, Yongping [1 ,2 ]
Liu, Kangdong [3 ,6 ,7 ]
Fang, Baijun [1 ,2 ]
机构
[1] Zhengzhou Univ, Affiliated Canc Hosp, Dept Hematol, Zhengzhou 450008, Henan, Peoples R China
[2] Henan Canc Hosp, Henan Hematol Inst, Zhengzhou 450008, Henan, Peoples R China
[3] China US Henan Hormel Canc Inst, Zhengzhou 450001, Henan, Peoples R China
[4] Zhengzhou Univ, Affiliated Canc Hosp, Dept Head & Neck Thyroid, Zhengzhou, Henan, Peoples R China
[5] Henan Canc Hosp, Zhengzhou, Henan, Peoples R China
[6] Zhengzhou Univ, Sch Basic Med Sci, Dept Pathophysiol, Zhengzhou 450001, Henan, Peoples R China
[7] Canc Chemoprevent Int Collaborat Lab, Zhengzhou 450001, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
LMLN; miR‐ 17‐ 3p; multiple myeloma; p21; plasma biomarker;
D O I
10.1002/ijc.33528
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3071 / 3085
页数:15
相关论文
共 50 条
  • [1] PRAME promotes proliferation of multiple myeloma cells through CTMP/Akt/p21/CCND3 axis by ubiquitinating CTMP and p21
    Sun, Kai
    Yang, Lu
    Wang, Feng
    Liu, Ying
    Xu, Nan
    Shi, Zong-Yan
    Chen, Wen-Min
    Li, Ke
    Qin, Ya-Zhen
    HELIYON, 2024, 10 (13)
  • [2] MiR-17-3p inhibits osteoblast differentiation by downregulating Sox6 expression
    Chen, Nan
    Wu, Di
    Li, Hua
    Liu, Yi
    Yang, Hao
    FEBS OPEN BIO, 2020, 10 (11): : 2499 - 2506
  • [3] Trichostatin A promotes GLI1 degradation and P21 expression in multiple myeloma cells
    Geng, Yan
    Liu, Jing
    Xie, Ying
    Jiang, Hongmei
    Zuo, Kai
    Li, Tao
    Liu, Zhiqiang
    CANCER MANAGEMENT AND RESEARCH, 2018, 10 : 2905 - 2914
  • [4] MiR-17-5p promotes cancer cell proliferation and tumorigenesis in nasopharyngeal carcinoma by targeting p21
    Chen, Chun
    Lu, Zenghong
    Yang, Jie
    Hao, Weichao
    Qin, Yujuan
    Wang, Huiyan
    Xie, Congying
    Xie, Raoying
    CANCER MEDICINE, 2016, 5 (12): : 3489 - 3499
  • [5] A novel human TINP1 gene promotes cell proliferation through inhibition of p53 and p21 expression
    Li, Wei
    Song, Ai-Ping
    Zhao, Fang
    Hu, Yong-Mei
    Hua, Mu
    ONCOLOGY REPORTS, 2013, 30 (04) : 1848 - 1852
  • [6] miR-17-3P regulates the proliferation and survival of colon cancer cells by targeting Par4
    Lu, Debao
    Tang, Liang
    Zhuang, Yan
    Zhao, Peng
    MOLECULAR MEDICINE REPORTS, 2018, 17 (01) : 618 - 623
  • [7] EZH2 promotes gastric cancer cells proliferation by repressing p21 expression
    Xu, Jiewei
    Wang, Zhong
    Lu, Wei
    Jiang, Hao
    Lu, Jun
    Qiu, Jian
    Ye, Guochao
    PATHOLOGY RESEARCH AND PRACTICE, 2019, 215 (06)
  • [8] Long Noncoding RNA PVT1 Promotes EMT and Cell Proliferation and Migration Through Downregulating p21 in Pancreatic Cancer Cells
    Wu, Bao-Qiang
    Jiang, Yong
    Zhu, Feng
    Sun, Dong-Lin
    He, Xiao-Zhou
    TECHNOLOGY IN CANCER RESEARCH & TREATMENT, 2017, 16 (06) : 819 - 827
  • [9] A novel human TINP1 gene promotes cell proliferation by inhibition of p53 and p21 expression
    Li, Wei
    Hu, Yongmei
    Song, Aiping
    INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2015, 36 : S108 - S108
  • [10] MiR-17-3p Inhibits Angiogenesis by Downregulating Flk-1 in the Cell Growth Signal Pathway
    Yin, Runting
    Wang, Rubing
    Guo, Le
    Zhang, Wei
    Lu, Yong
    JOURNAL OF VASCULAR RESEARCH, 2013, 50 (02) : 157 - 166