|Table of Contents|

MTDH interference promotes drug sensitivity and cell apoptosis in glioma resistant to temozolomide

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 14
Page:
2530-2534
Research Field:
Publishing date:

Info

Title:
MTDH interference promotes drug sensitivity and cell apoptosis in glioma resistant to temozolomide
Author(s):
MENG Liang1; WANG Yuefei1; TAO Liang1; FAN Wen1; TU Qin1; ZHU Yuan1; YU Xiaoxiang1; DAI Xiaoqin2
1.Department of Neurosurgery;2.120 Treatment Center,Wuhan Third Hospital,Hubei Wuhan 430061,China.
Keywords:
glioma; MTDH; apoptosis; drug sensitivity; AKT1 pathway
PACS:
R739.41
DOI:
10.3969/j.issn.1672-4992.2024.14.006
Abstract:
Objective:To investigate whether metadherin (MTDH) interference can promote cell apoptosis by improving the drug sensitivity of glioma temozolomide (TMZ)-resistant strains.Methods:Based on the cultured U251 human glioma cells and U251MG/TMZ human astroglioma cells resistant to temozolomide,the expressions of MTDH,miR-1471 and miR-153-3p in the cells were detected by qRT-PCR.siRNA/NC was synthesized according to the sequence of human MTDH and transfected into U251MG/TMZ cells.Cell proliferation ability was detected by CCK8.Cell apoptosis was detected by flow cytometry.The expression of drug resistance-related genes was detected by Western blot.U251MG/TMZ cells transfected with si-MTDH/NC were treated with different concentrations of temozolomide (2.5,5,10,20,40,80,160 μmol/L),and cell proliferation was detected by CCK8 method after 48 h.Results:U251MG/TMZ cells had high expression of MTDH,low expression of miR-1471 and miR-153-3p.Compared with the Control group,the proliferation ability of cells in the U251MG/TMZ group was significantly increased,the apoptosis rate was significantly reduced,the mRNA expressions of MTDH,ABCG2,MGMT and Pgp were significantly increased,and the protein expressions of MTDH,ABCB1,MGMT,ABCG2 and p-AKT1 were significantly increased.Compared with the NC group,the proliferation ability of cells in the si-MTDH group was significantly decreased,the apoptosis rate was significantly increased,the mRNA expressions of MTDH,ABCG2,MGMT and Pgp were significantly decreased,and the protein expressions of MTDH,ABCB1,MGMT,ABCG2 and p-AKT1 were significantly decreased.Conclusion:MTDH interference promotes cell apoptosis by increasing the drug sensitivity of glioma resistant to temozolomide,and the mechanism may be related to the AKT1 pathway.

References:

[1]XU S,TANG L,LI X,et al.Immunotherapy for glioma:Current management and future application［J］.Cancer Lett,2020,476:1-12.
[2]DI NUNNO V,GATTO L,TOSONI A,et al.Implications of BRAF V600E mutation in gliomas:Molecular considerations,prognostic value and treatment evolution［J］.Front Oncol,2023,12:1067252.
[3]FRIEDRICH M,HAHN M,MICHEL J,et al.Dysfunctional dendritic cells limit antigen-specific T cell response in glioma［J］.Neuro Oncol,2023,25(2):263-276.
[4]ZHANG XN,YANG KD,CHEN C,et al.Pericytes augment glioblastoma cell resistance to temozolomide through CCL5-CCR5 paracrine signaling［J］.Cell Res,2021,31(10):1072-1087.
[5]DHIMAN G,SRIVASTAVA N,GOYAL M,et al.Metadherin:a therapeutic target in multiple cancers［J］.Front Oncol,2019,9:349.
[6]吴云,沙琳琳.MTDH和PDCD10在结直肠癌组织中的表达及临床意义［J］.中国现代普通外科进展,2017,20(09):677-679，683. WU Y,SHA LL.Expression and clinical significance of MTDH and PDCD10 in colorectal cancer tissues［J］.Progress of Modern General Surgery in China,2017,20(09):677-679，683.
[7]NGUYEN YT,MOON JY,EDIRIWEERA MK,et al.Phenethyl isothiocyanate suppresses stemness in the chemo- and radio-resistant triple-negative breast cancer cell line MDA-MB-231/IR via downregulation of metadherin［J］.Cancers (Basel),2020,12(2):268.
[8]MENG L,CHEN Q,CHEN Z,et al.microRNA-1471 suppresses glioma cell growth and invasion by repressing metadherin expression［J］.Int J Clin Exp Pathol,2018,11(12):5909-5915.
[9]FU J,PENG J,TU G.Knockdown MTDH inhibits glioma proliferation and migration and promotes apoptosis by downregulating MYBL2［J］.Mediators Inflamm,2022,2022:1706787.
[10]MOLINARO AM,TAYLOR JW,WIENCKE JK,et al.Genetic and molecular epidemiology of adult diffuse glioma［J］.Nat Rev Neurol,2019,15(7):405-417.
[11]YOU F,LI C,ZHANG S,et al.Sitagliptin inhibits the survival,stemness and autophagy of glioma cells,and enhances temozolomide cytotoxicity［J］.Biomed Pharmacother,2023,162:114555.
[12]韩刚，杨扬，胡胜利.替莫唑胺通过调控miR-216a/PRKCA抑制胶质瘤细胞U251增殖和侵袭作用的研究［J］.现代肿瘤医学，2019，27(10):1713-1717. HAN G,YANG Y,HU SL.Inhibitory effect of temozolomide on proliferation and invasion of glioma cell line U251 by regulating miR-216a/PRKCA［J］.Modern Oncology，2019，27(10):1713-1717.
[13]戴小琴,孟亮,王跃飞,等.miR-1471对胶质瘤细胞增殖,侵袭和迁移能力的影响及其机制探讨［J］.现代肿瘤医学,2023,31(3):407-411. DAI XQ,MENG L,WANG YF,et al.Effects of miR-1471 on the proliferation,invasion and migration of glioma cells and its mechanism［J］.Modern Oncology,2023,31(3):407-411.
[14]SUN D,MU Y,PIAO H.MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma［J］.Biol Res,2018,51(1):56.
[15]PENG KL,VASUDEVAN HN,LOCKNEY DT,et al.Miat and interacting protein Metadherin maintain a stem-like niche to promote medulloblastoma tumorigenesis and treatment resistance［J］.Proc Natl Acad Sci USA,2022,119(37):e2203738119.
[16]TONG L,CHU M,YAN B,et al.MTDH promotes glioma invasion through regulating miR-130b-ceRNAs［J］.Oncotarget,2017,8(11):17738-17749.
[17]LIU X,CHEN J,LI W,et al.Inhibition of casein kinase II by CX-4945,but not yes-associated protein (YAP) by verteporfin,enhances the antitumor efficacy of temozolomide in glioblastoma［J］.Transl Oncol,2020,13(1):70-78.
[18]BUTLER M,PONGOR L,SU YT,et al.MGMT status as a clinical biomarker in glioblastoma［J］.Trends Cancer,2020,6(5):380-391.
[19]PASTVOVA N,DOLEZEL P,MLEJNEK P.Heat shock protein inhibitor 17-allyamino-17-demethoxygeldanamycin,a potent inductor of apoptosis in human glioma tumor cell lines,is a weak substrate for ABCB1 and ABCG2 transporters［J］.Pharmaceuticals (Basel),2021,29,14(2):107.
[20]MAJEWSKA E SZELIGA M.AKT/GSK3β signaling in glioblastoma［J］.Neurochem Res,2017,42(3):918-924.
[21]WANG Y,XIE X,LI S,et al.Co-overexpression of RIOK1 and AKT1 as a prognostic risk factor in glioma［J］.J Cancer,2021,12(19):5745-5752.

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湖北省武汉市科技局2022年度知识创新专项基础研究项目（编号:2022020801010549）
Last Update: 1900-01-01