Volume 20 Issue 5
May  2022
Turn off MathJax
Article Contents
Article Navigation >  Chinese Journal of General Practice  > 2022  >  20(5): 745-748
LI Guang-bao, YIN Jian-wen, ZHANG Yi-qun, LI Shi-zhong, WU Zu-tong, HE Ai-jun. Mechanism of miRNA-19a targeting the SMO gene regulates the hedgehog signalling pathway and affects the biological characteristics of myeloma cells[J]. Chinese Journal of General Practice, 2022, 20(5): 745-748. doi: 10.16766/j.cnki.issn.1674-4152.002444
Citation: LI Guang-bao, YIN Jian-wen, ZHANG Yi-qun, LI Shi-zhong, WU Zu-tong, HE Ai-jun. Mechanism of miRNA-19a targeting the SMO gene regulates the hedgehog signalling pathway and affects the biological characteristics of myeloma cells[J]. Chinese Journal of General Practice, 2022, 20(5): 745-748. doi: 10.16766/j.cnki.issn.1674-4152.002444
shu

Mechanism of miRNA-19a targeting the SMO gene regulates the hedgehog signalling pathway and affects the biological characteristics of myeloma cells

doi: 10.16766/j.cnki.issn.1674-4152.002444

  • Department of Orthopaedics, the First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan 422000, China

Funds:

 19C1636

  • Received Date: 2021-07-03
    Available Online: 2022-09-05
    Abstract
  •   Objective  To explore the effects of miRNA-19a on the proliferation, apoptosis and metastasis of multiple myeloma cells, as well as on smoothened frizzled class receptor(SMO) protein and the hedgehog signalling pathway.  Methods  Human myeloma cell lines U266b1, LP-1, RPMI 8226 and NCI-H929 were used as the research models. Firstly, the background expression of SMO protein in four kinds of cells was detected. Using U266b1 cells as the model, the miRNA-19a inhibitor was designed, and the miRNA-19a knockdown group, control plasmid group and empty group were established. Changes in the SMO protein content, cell proliferation, apoptosis and metastasis were explored after miRNA-19a knockdown. Cytotoxicity was detected by MTT assay, apoptosis was detected by flow cytometry and cell invasion was detected by Transwell test.  Results  The expression levels of SMO protein in the U266b1, LP-1, RPMI 8226 and NCI-H929 cell lines were 0.925±0.057, 0.889±0.067, 0.904±0.075, and 0.507±0.048, respectively, whereas the expression level of SMO protein in the NCI-H929 cell line was low (P < 0.05). The miRNA-19a contents in the miRNA-19a knockdown group, control plasmid group and empty group were 0.325±0.058, 1.158±0.128 and 1.172±0.131, respectively. The miRNA-19a contents in the miRNA-19a knockdown group decreased significantly (P < 0.05). The expression levels of SMO in the control plasmid group, miRNA-19a knockdown group and empty group were 0.787±0.104, 0.354±0.068 and 0.807±0.106, respectively. The content of SMO protein in the miRNA-19a knockdown group decreased significantly (P < 0.05). MTT assay showed that the OD value of cell proliferation in the miRNA-19a knockdown group was significantly lower than that in the empty group and control plasmid group within 24-72 h (all P < 0.05). Apoptosis experiments showed that the apoptosis rate of the miRNA-19a knockdown group was significantly higher than that of the empty group and control plasmid group (all P < 0.05). Transwell experiments showed that the number of invasive cells in the miRNA-19a knockdown group was significantly lower than that in the two other groups (all P < 0.05).  Conclusion  miRNA-19a/SMO protein may be the key signal to control the malignant growth of cells in myeloma cell line U266b1. It can be used as a potential target for the treatment of multiple myelomas.

     

    • FullText(HTML)
  • loading
    • References(19)
  • [1]
    MIAN H, BROUWERS M, KOUROUKIS C T, et al. Comparison of frailty scores in newly diagnosed patients with multiple myeloma: A review[J]. J Frailty Aging, 2019, 8(4): 215-221.
    [2]
    ZHANG L, ZHOU L, SHI M, et al. Downregulation of miRNA-15a and miRNA-16 promote tumor proliferation in multiple myeloma by increasing CABIN1 expression[J]. Oncology letters, 2018, 15(1): 1287-1296.
    [3]
    岳智杰, 张小影, 赵盼, 等. 多发性骨髓瘤患者骨髓瘤细胞中miRNA-19a的表达水平及其对骨髓瘤细胞相关特性的影响[J]. 中国实验血液学杂志, 2018, 26(2): 464-469. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201802031.htm

    QIU Z J, ZHANG X Y, ZHAO P, et al. Expression of miRNA-49a in cells of multiple myeloma patients and its effect on the characteristics of myeloma cells[J]. Journal of Experimental Hematology, 2018, 26(2): 464-469. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201802031.htm
    [4]
    NATONI A, BOHARA R, PANDIT A, et al. Targeted approaches to inhibit sialylation of multiple myeloma in the bone marrow microenvironment[J]. Front Bioeng Biotechnol, 2019, 7(100): 252-259.
    [5]
    丁飞, 朱平, 伍学强. 多发性骨髓瘤发病的分子机理和恶性克隆演化[J]. 中国实验血液学杂志, 2015, 23(5): 1513-1516. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201505059.htm

    DING F, ZHU P, WU X Q. Molecular mechanism and malignant clonal evolution of multiple myeloma: Review[J]. Journal of Experimental Hematology, 2015, 23(5): 1513-1516. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201505059.htm
    [6]
    FIRTH J. Haematology: Multiple myeloma[J]. Clin Med, 2019, 19(1): 58-60. doi: 10.7861/clinmedicine.19-1-58
    [7]
    ACQUAVELLA J, GARABRANT D, MARSH G, et al. Glyphosate epidemiology expert panel review: A weight of evidence systematic review of the relationship between glyphosate exposure and non-Hodgkin's lymphoma or multiple myeloma[J]. Crit Rev Toxicol, 2016, 46(Suppl 1): 28-43.
    [8]
    ROBAK P, DROZDZ I, SZEMRAJ J, et al. Drug resistance in multiple myeloma[J]. Cancer Treat Rev, 2018, 70: 199-208. doi: 10.1016/j.ctrv.2018.09.001
    [9]
    尚晋, 陈志忠, 王志红, 等. miRNA-196b-5p和miRNA-99a-5p对多发性骨髓瘤细胞自噬及凋亡的影响[J]. 中华血液学杂志, 2018, 39(9): 766-772.

    SHANG J, CHEN Z Z, WANG Z H, et al. Effects of miRNA-196b-5p and miRNA-99a-5p on autophagy and apoptosis of multiple myeloma cells[J]. Chinese Journal of Hematology, 2018, 39(9): 766-772.
    [10]
    尚晋, 陈志忠, 王志红, 等. miRNA-132、miRNA-125b、miRNA-143和miRNA-145表达对多发性骨髓瘤细胞自噬及凋亡的影响[J]. 中国实验血液学杂志, 2018, 26(6): 1688-1694. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201806021.htm

    SHANG J, CHEN Z Z, WANG Z H, et al. Effects of miRNA-132, miRNA-125b, miRNA-143 and miRNA-145 expression on autophagy and apoptosis of multiple myeloma cells[J]. Journal of Experimental Hematology, 2018, 26(6): 1688-1694. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201806021.htm
    [11]
    JIN N, ZHU X J, CHENG F J, et al. Disulfiram/copper targets stem cell-like ALDH(+) population of multiple myeloma by inhibition of ALDH1A1 and Hedgehog pathway[J]. J Cell Biochem, 2018, 119(8): 6882-6893. doi: 10.1002/jcb.26885
    [12]
    XIE Y, LIU J, JIANG H M, et al. Proteasome inhibitor induced SIRT1 deacetylates GLI2 to enhance hedgehog signaling activity and drug resistance in multiple myeloma[J]. Oncogene, 2020, 39(4): 922-934. doi: 10.1038/s41388-019-1037-6
    [13]
    KESIREDDY M, MENDIOLA V L, JANA B G, et al. Long-term response to vismodegib in a patient with Gorlin-Goltz syndrome: A case report and review of pathological mechanisms involved[J]. Cureus, 2019, 11(8): 582-591.
    [14]
    WANG J, CHAN D K W, SEN A, et al. Tumor priming by SMO inhibition enhances antibody delivery and efficacy in a pancreatic ductal adenocarcinoma model[J]. Mol Cancer Ther, 2019, 18(11): 2074-2084. doi: 10.1158/1535-7163.MCT-18-0354
    [15]
    ZHANG X Y, CHEN Y F, ZHAO P, et al. MicroRNA-19a functions as an oncogene by regulating PTEN/AKT/pAKT pathway in myeloma[J]. Leuk Lymphoma, 2017, 58(4): 932-940. doi: 10.1080/10428194.2016.1213827
    [16]
    QU C, LIU Y, KUNKALLA, K, et al. Smoothened (SMO), a G-Protein-Coupled Receptor (GPCR) activated by hedgehog ligands, modulates the activity levels of PI3K/AKT and NF-K in diffuse large b-cell lymphoma[J]. Blood, 2011, 118(21): 3483. doi: 10.1182/blood.V118.21.3483.3483
    [17]
    岳智杰, 张小影, 赵盼, 等. 多发性骨髓瘤患者骨髓瘤细胞中miRNA-19a的表达水平及其对骨髓瘤细胞相关特性的影响[J]. 中国实验血液学杂志, 2018, 26(2): 464-469. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201802031.htm

    YUE Z J, ZHANG X Y, ZHAO P, et al. Expression level of mirna-19a in myeloma cells of patients with multiple myeloma and its effect on relevant characteristics of myeloma cells[J]. Journal of Experimental Hematology, 2018, 26(2): 464-469. https://www.cnki.com.cn/Article/CJFDTOTAL-XYSY201802031.htm
    [18]
    YIN Z, YANG J, NING R, et al. Signal pathways, diseases, and functions associated with the miR-19a/92a cluster and the use of berberine to modulate the expression of this cluster in multiple myeloma cells[J]. J Biochem Mol Toxic, 2018, 13(15): 325-332.
    [19]
    保秋萍, 李惠民, 李晓进, 等. 多发性骨髓瘤U266细胞株中侧群细胞的生物学特性与耐药性的关系[J]. 中国组织工程研究, 2017, 21(29): 4648-4653. doi: 10.3969/j.issn.2095-4344.2017.29.010

    BAO Q P, LI H M, LI X J, et al. Relationship between biological characteristics and drug resistance of lateral population cells in U266 cell line of multiple myeloma[J]. China Tissue Engineering Research, 2017, 21(29): 4648-4653. doi: 10.3969/j.issn.2095-4344.2017.29.010
    • Relative Articles
    • Supplements(0)
    • Cited By
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(4)

    Get Citation
    PDF
    XML

    Article Metrics

    Article views (205) PDF downloads(4) Cited by()
    Proportional views
    Related

    Address：No. 287, Changhuai Road, Bengbu, Anhui Province, 233004, P.R.ChinaphoneNo：0552-3066635； 0552-3051890Email：zhqkyx@163.com

    Copyright © Chinese Journal of General Practice皖ICP备2020018345号-2

    Supported by: Beijing Renhe Information Technology Co., Ltd.    

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return