Influence of targeted inhibition of DNAJC1 gene on apoptosis and proliferation in multiple myeloma cells

Bihui YANG; Guoyu HU; Chanjuan SHEN; Zhenzhen CHEN; Haimei CHEN; Zhao LIU

doi:10.16016/j.1000-5404.202104054

您当前的位置：

首页 >

文章列表页 >

Influence of targeted inhibition of DNAJC1 gene on apoptosis and proliferation in multiple myeloma cells

Basic Medicine | 更新时间：2026-01-09

- Influence of targeted inhibition of DNAJC1 gene on apoptosis and proliferation in multiple myeloma cells
- Journal of Third Military Medical University Vol. 43, Issue 19, Pages: 1894-1898(2021)
- 作者机构：
  
  1.412007 湖南株洲，湖南省株洲市中心医院: 血液科
  2.412007 湖南株洲，湖南省株洲市中心医院: 重症医学科
- 作者简介：
- 基金信息：
  
  the Guidance Project for Clinical Medical Technology Innovation of Hunan Provincial Technology Innovation Guidance Plan(2018SK52805)
- DOI：10.16016/j.1000-5404.202104054
  CLC： R394.3;R73-362;R733.3
- Received：09 April 2021，
  
  Revised：2021-05-18，
  
  Published：15 October 2021
- 稿件说明：
移动端阅览
Bihui YANG, Guoyu HU, Chanjuan SHEN, et al. Influence of targeted inhibition of DNAJC1 gene on apoptosis and proliferation in multiple myeloma cells[J]. Journal of Third Military Medical University, 2021, 43(19): 1894-1898.
DOI：

Bihui YANG, Guoyu HU, Chanjuan SHEN, et al. Influence of targeted inhibition of DNAJC1 gene on apoptosis and proliferation in multiple myeloma cells[J]. Journal of Third Military Medical University, 2021, 43(19): 1894-1898. DOI： 10.16016/j.1000-5404.202104054.

摘要

目的

研究DNAJC1基因对多发性骨髓瘤细胞增殖及凋亡的影响，初步探讨其作用机制。

方法

将DNAJC1-siRNA及阴性对照siRNA转染人多发性骨髓瘤细胞株U266，利用RT-qPCR及Western blot验证DNAJC1基因干扰效果，CCK-8检测DNAJC1基因对U266细胞增殖的影响，流式细胞仪检测其对细胞凋亡的影响。RT-qPCR及Western blot检测 U266 细胞中 PTEN mRNA及蛋白表达。

结果

干扰组DNAJC1基因mRNA及蛋白表达明显降低

U266细胞的增殖明显受抑

抑制率为(58.95± 8.13)%

与阴性siRNA组相比差异有统计学意义(

0.05)。干扰组细胞凋亡率为(44.95±6.06)%

明显高于阴性siRNA

组[(3.91±0.38)%

]

及对照组[(3.97±0.43)%

0.05

]

。与阴性siRNA组相比

干扰组PTEN的mRNA及蛋白表达明显升高(

0.05)。

结论

靶向抑制DNAJC1基因可促进多发性骨髓瘤细胞的凋亡，抑制其增殖，这种作用可能是通过上调PTEN水平来实现的。

Abstract

Objective

To determine the effect of DNAJC1 gene on the proliferation and apoptosis of multiple myeloma cell lines and preliminarily investigate its mechanism.

Methods

DNAJC1-siRNA and its negative control (siRNA) were transfected into human multiple myeloma cell line U266 respectively. The interference efficiency was determined by RT-qPCR and Western blotting

and cell proliferation and apoptotic rate were measured with CCK-8 assay and flow cytometry

respectively. In addition

RT-qPCR and Western blotting were also used to examine the mRNA and protein expression of PTEN in U266 cells.

Results

The mRNA and protein levels of DNAJC1 were downregulated in the interference group. The proliferation of U266 cells was inhibited significantly in the interference group

with an inhibitory rate of (58.95±8.13)%

apparently higher than that of the negative siRNA group (

0.05). The apoptotic rate was (44.95±6.06)% in the interference group

which notably exceeded that of the negative siRNA group and the control group (

0.05). The mRNA and protein levels of PTEN were significantly increased in the interference group (

0.05).

Conclusion

Targeted inhibition of DNAJC1 gene can promote the apoptosis and inhibit the proliferation in multiple myeloma cells

which may be mediated by up-regulation of PTEN.

关键词

Keywords

references

WANG S, XU L, FENG J, et al . Prevalence and incidence of multiple myeloma in urban area in China: a national population-based analysis[J ] . Front Oncol, 2019, 9: 1513. DOI:10.3389/fonc.2019.01513.

RAJKUMAR S V. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management [J]. Am J Hematol, 2020, 95(5): 548-567. DOI:10.1002/ajh.25791.

BLAU M, MULLAPUDI S, BECKER T, et al . ERj1p uses a universal ribosomal adaptor site to coordinate the 80S ribosome at the membrane[J ] . Nat Struct Mol Biol, 2005, 12(11): 1015-1016. DOI:10.1038/nsmb998.

DUDEK J, GREINER M, MVLLER A, et al . ERj1p has a basic role in protein biogenesis at the endoplasmic Reticulum[J ] . Nat Struct Mol Biol, 2005, 12(11): 1008-1014. DOI:10.1038/nsmb1007.

POMPEIA C, HODGE D R, PENG B, et al . Epigenetic up-regulation of gene expression in KAS 6/1 human multiple myeloma cells[J ] . Cancer Genom Proteom, 2004, 1(5/6): 387-406.

MISRA U K, GONZALEZ-GRONOW M, GAWDI G, et al . The role of MTJ-1 in cell surface translocation of GRP78, a receptor for alpha 2-macroglobulin-dependent signaling[J ] . J Immunol, 2005, 174(4): 2092-2097. DOI:10.4049/jimmunol.174.4.2092.

LEE A S. Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential[J]. Nat Rev Cancer, 2014, 14(4): 263-276. DOI:10.1038/nrc3701.

WEY S, LUO B, TSENG C C, et al . Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling[J ] . Blood, 2012, 119(3): 817-825. DOI:10.1182/blood-2011-06-357384.

杨碧慧, 张玉琳, 王利, 等. SPAG6基因RNAi慢病毒载体的构建及其对SKM-1细胞凋亡的影响[J]. 第三军医大学学报, 2015, 37(5): 474-479. DOI: 10.16016/j.1000-5404.201408199.

YANG B H, ZHANG Y L, WANG L, et al . Construction of lentiviral vector for SPAG6 RNA interference and its influence on apoptosis of SKM-1 cells[J ] . J Third Mil Med Univ, 2015, 37(5): 474-479. DOI: 10.16016/j.1000-5404.201408199.

PHAROAH P D, TSAI Y Y, RAMUS S J, et al . GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer[J ] . Nat Genet, 2013, 45(4): 362-370. DOI:10.1038/ng.2564.

SHI J, SUNG H, ZHANG B, et al . New breast cancer risk variant discovered at 10q25 in East Asian women[J ] . Cancer Epidemiol Biomarkers Prev, 2013, 22(7): 1297-1303. DOI:10.1158/1055-9965.epi-12-1393.

JUNG J J, JEUNG H C, CHUNG H C, et al . In vitro pharmaco genomic database and chemosensitivity predictive genes in gastric cancer[J ] . Genomics, 2009, 93(1): 52-61. DOI:10.1016/j.ygeno.2008.08.002..

WANG L, FIDLER C, NADIG N, et al . Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays[J ] . Haematologica, 2008, 93(7): 994-1000. DOI:10.3324/haematol.12603.

MULAW M A, KRAUSE A, DESHPANDE A J, et al . CALM/AF10-positive leukemias show upregulation of genes involved in chromatin assembly and DNA repair processes and of genes adjacent to the breakpoint at 10p12[J ] . Leukemia, 2012, 26(5): 1012-1019. DOI:10.1038/leu.2011.307.

CARRASCO D R, TONON G, HUANG Y, et al . High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients[J ] . Cancer Cell, 2006, 9(4): 313-325. DOI:10.1016/j.ccr.2006.03.019.

CHEVALIER M, RHEE H, ELGUINDI E C, et al . Interaction of murine BiP/GRP78 with the DnaJ homologue MTJ1[J ] . J Biol Chem, 2000, 275(26): 19620-19627. DOI:10.1074/jbc.m001333200.

CASAS C. GRP78 at the centre of the stage in cancer and neuroprotection[J]. Front Neurosci, 2017, 11: 177. DOI:10.3389/fnins.2017.00177.

MISRA U K, MOWERY Y M, GAWDI G, et al . Loss of cell surface TFⅡ-Ⅰ promotes apoptosis in prostate cancer cells stimulated with activated α 2 -macroglobulin[J ] . J Cell Biochem, 2011, 112(6): 1685-1695. DOI:10.1002/jcb.23083..

ZHANG J, GRINDLEY J C, YIN T, et al . PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention[J ] . Nature,2006, 441(7092): 518-522. DOI:10.1038/nature04747.

GE N L, RUDIKOFF S. Expression of PTEN in PTEN-deficient multiple myeloma cells abolishes tumor growth in vivo [J ] . Oncogene, 2000, 19(36): 4091-4095. DOI:10.1038/sj.onc.1203801.

HYUN T, YAM A, PECE S, et al . Loss of PTEN expression leading to high Akt activation in human multiple myelomas[J ] . Blood, 2000, 96(10): 3560-3568. DOI:10.1182/blood.V96.10.3560.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of abnormal specification of spermatogonial stem cells after Rb1 knockout in mitotic-arrested prospermatogonia

Biological clock gene PER1 regulates circadian rhythms of BAX, BCL2 and PCNA expression in oral squamous carcinoma cells

Effect of protease activated receptor 2 on proliferation and apoptosis of hepatocellular carcinoma cells

Related Author

CHEN Xinling

LONG Yixuan

DU Guihua

CHEN Xinling

LONG Yixuan

DU Guihua

Shilin YIN

Zhiwei ZHANG

Related Institution

Department of Occupational Health and Toxicology， School of Public Health, Nanchang University

Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University

Department of Occupational Health and Toxicology， School of Public Health

Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health， Nanchang University

Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University

⁰