Journal of Shanghai Jiao Tong University (Medical Science) ›› 2022, Vol. 42 ›› Issue (7): 858-865.doi: 10.3969/j.issn.1674-8115.2022.07.003

• Basic research • Previous Articles    

SMAD7 expression in multiple myeloma and its effect on cell proliferation and drug resistance

DING He1(), CAO Yanglin2, HE Yang2, WEI Xing3, YANG Jianfeng1()   

  1. 1.Hematology Center, Cyrus Tang Medical Institute, Suzhou Medical College of Soochow University, Suzhou 215123, China
    2.The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou 215006, China
    3.Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
  • Received:2022-03-07 Accepted:2022-06-24 Online:2022-07-28 Published:2022-09-04
  • Contact: YANG Jianfeng E-mail:1838872960@qq.com;yangjianfeng@suda.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81673096)

Abstract: Objective

·To analyze the expression of Sma- and Mad-related protein 7 (SMAD7) in multiple myeloma (MM), and its effect on the proliferation and drug resistance of MM cells.

Methods

·Three datasets from the Gene Expression Omnibus (GEO) database were obtained to analyze the differential expression of SMAD7 in healthy donors and MM. Bone marrow samples from 8 healthy donors and 20 MM patients were collected. The relative expression of SMAD7 mRNA in bone marrow CD138+ cells was detected by quantitative real-time PCR (qPCR), and the relationship between SMAD7 mRNA expression and clinical information of patients was analyzed. After overexpression of SMAD7 in MM cells KMS11, the effects of SMAD7 on the proliferation was observed by CCK8 assay and cell cycle assay. KMS11 cells overexpressing SMAD7 were treated with different concentrations of bortezomib, and the effect of SMAD7 on drug resistance and apoptosis of MM cells were observed.

Results

·The analysis of SMAD7 expression data in the datasets showed that compared with healthy donors, SMAD7 expression in MM patients was higher (all P<0.05). The results of qPCR showed that the relative expression of SMAD7 mRNAwas up-regulated in MM patients (P=0.002), although no correlation with clinical information of patients was shown. Compared with the control cells, the cell viability of KMS11 was higher after overexpression of SMAD7 (all P<0.05); the change of cell cycle distribution showed that the proportion of cells in S phase decreased (P=0.016), and the proportion of cells in G2/M phase increased (P=0.005); after bortezomib treatment, the drug sensitivity and apoptosis level of overexpression SMAD7 cells was lower.

Conclusion

·The expression of SMAD7 is up-regulated in MM. Overexpression of SMAD7 can promote the proliferation and drug resistance of MM cells.

Key words: Sma- and Mad-related protein 7 (SMAD7), multiple myeloma (MM), cell proliferation, bortezomib

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