|Table of Contents|

The effect of lncRNA LINC02381 on temozolomide resistance of glioma cells through the miR-133a-3p/MGMT axis

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

Issue:
2023 20
Page:
3751-3757
Research Field:
Publishing date:

Info

Title:
The effect of lncRNA LINC02381 on temozolomide resistance of glioma cells through the miR-133a-3p/MGMT axis
Author(s):
CHEN Jing; DONG Shanwu; TAO Shuang; LUO Chao; CHEN Ling; LIU Na; FU Yang
Department of Pediatrics,Wuhan Fourth Hospital,Hubei Wuhan 430000,China.
Keywords:
glioma; lncRNA LINC02381; miR-133a-3p; MGMT
PACS:
R739.41
DOI:
10.3969/j.issn.1672-4992.2023.20.006
Abstract:
Objective:To investigate the effect of lncRNA LINC02381 on the resistance of glioma cells to temozolomide (TMZ) through the miR-133a-3p/MGMT axis.Methods:Human glioma cell lines U251 and TMZ-resistant cells U251/TR were cultured in vitro,and U251/TR cells were divided into U251/TR group,si-NC group,si-LINC02381 group,mimics NC group,miR-133a-3p mimics group,miR-133a-3p mimics+pcDNA3.1 group,miR-133a-3p mimics+pcDNA3.1 LINC02381 group,and miR-133a-3p mimics+pcDNA3.1 MGMT group.CCK-8 method was performed to measure the resistance of U251 and U251/TR cells to TMZ.qRT-PCR was performed to measure the levels of LINC02381,miR-133a-3p,and MGMT.Flow cytometry was performed to measure cell apoptosis.Dual luciferase report experiment was performed to verify the targeting relationship between LINC02381 and miR-133a-3p,between miR-133a-3p and MGMT.Western blot method was performed to measure the protein expression of Bax,Bcl-2,Cleaved-caspase 3 and MGMT.Results:Compared with U251 cells,IC50,the expression of LINC02381 and MGMT mRNA,MGMT protein expression in U251/TR cells increased (P＜0.05),and the expression of miR-133a-3p decreased (P＜0.05).Compared with U251/TR group and mimics NC group,the Bcl-2 expression in miR-133a-3p mimics group decreased (P＜0.05),and the miR-133a-3p expression,cell apoptosis rate,the expression of Bax and Cleaved-caspase 3 increased (P＜0.05).Compared with the U251/TR group and the si-NC group,the expression of LINC02381 and Bcl-2 in the si-LINC02381 group decreased (P＜0.05),and the cell apoptosis rate,the expression of Bax and Cleaved-caspase 3 increased (P＜0.05).miR-133a-3p had a targeting relationship with LINC02381 and MGMT.Both LINC02381 and MGMT overexpression could reverse the effect of miR-133a-3p overexpression on the TMZ resistance of U251/TR cells.Conclusion:The silencing of lncRNA LINC02381 may increase the expression of miR-133a-3p,thereby inhibiting the expression of MGMT and reducing the resistance of U251/TR cells to TMZ.

References:

[1] 王宏欣,付苏,淳雪莉,等.miR-4539通过靶向作用于叉头盒转录因子1抑制胶质瘤细胞生长的实验研究［J］.中国比较医学杂志,2022,32(5):91-97. WANG HX,FU S,CHUN XL,et al.miR-4539 inhibits the growth of glioma cells by targeting Foxp［J］.Chinese Journal of Comparative Medicine,2022,32(5):91-97.
[2] ZHANG D,ZHOU H,LIU J,et al.Long noncoding RNA ASB16-AS1 promotes proliferation,migration,and invasion in glioma cells［J］.Biomed Res Int,2019,2019:5437531.
[3] 刘正泰,肖方祥,王俊杰,等.LncRNA KCNQ1OT1在卵巢癌组织中的表达及对卵巢癌细胞顺铂耐药的作用［J］.肿瘤,2019,39(1):51-60. LIU ZT,XIAO FX,WANG JJ,et al.Expression of LncRNA KCNQ1OT1 in ovarian cancer tissues and its effect on cisplatin resistance in ovarian cancer cells［J］.Tumor,2019,39(1):51-60.
[4] 李吉,徐莹,褚以忞,等.lncRNA XIST-miR137-ATG5调节细胞自噬功能在肠癌细胞5-氟胞嘧啶耐药性中的作用［J］.现代生物医学进展,2020,20(19):3609-3615. LI J,XU Y,CHU YM,et al.LncRNA XIST-miR137-ATG5 mediate cell autophagy to attenuate 5-FU resistance in colorectal cancer cells to 5-FU［J］.Progress in Modern Biomedicine,2020,20(19):3609-3615.
[5]BIAN X,SUN YM,WANG LM,et al.ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503-5p［J］.Biochem Biophys Res Commun,2021,548:112-119.
[6] SUN Y,WANG X,BU X.LINC02381 contributes to cell proliferation and hinders cell apoptosis in glioma by transcriptionally enhancing CBX5［J］.Brain Res Bull,2021,176:121-129.
[7] GCZI D,NAGY B,SZILGYI M,et al.Analysis of circulating miRNA profile in plasma samples of glioblastoma patients［J］.Int J Mol Sci,2021,22(10):5058-5078.
[8] CHEN B,HE A,BI J,et al.Long-range gene regulation network of the MGMT enhancer modulates glioma cell sensitivity to temozolomide［J］.J Genet Genomics,2021,48(10):946-949.
[9]段然,颜成睿,王磊.lncRNA POU3F3通过调节MGMT的表达影响高级别脑胶质瘤细胞对替莫唑胺耐药［J］.中国肿瘤生物治疗杂志,2019,26(3):328-332. DUAN R,YAN CR,WANG L.IncRNA POU3F3 affects temozolomide-resistance in high-grade glioma cells via regulating MGMT expression［J］.Chinese Journal of Cancer Biotherapy,2019,26(3):328-332.
[10]丁吉涛,李明浩,李琳坤,等.替莫唑胺治疗神经胶质瘤患者疗效与安全性的回顾性分析［J］.现代肿瘤医学，2019,27(23):4187-4190. DING Jitao,LI Minghao,LI Linkun，et al.The curative effect and safe analysis of temozolomide for neuroglioma patients［J］.Modern Oncology,2019,27(23):4187-4190.
[11] 卫润斐，梁洪磊，曹付强，等.立体定向放射治疗联合替莫唑胺治疗复发性脑胶质瘤的疗效［J］.现代肿瘤医学，2021,29（13）：2261-2265. WEI Runfei,LIANG Honglei,CAO Fuqiang,et al.Efficacy of stereotactic radiotherapy combined with temozolomide in the treatment of recurrent glioma［J］.Modern Oncology,2021,29（13）：2261-2265.
[12]阮庆芬,杨德祥,杨理伟.miR-572对胃癌细胞增殖和凋亡影响及其作用机制研究［J］.中国比较医学杂志,2021,31(3):82-88. RUAN QF,YANG DX,YANG LW.Effects and mechanism of miR-572 on proliferation and apoptosis of gastric cancer cells［J］.Chinese Journal of Comparative Medicine,2021,31(3):82-88.
[13] WANG X,ZHU L,LIN X,et al.MiR-133a-3p inhibits the malignant progression of oesophageal cancer by targeting CDCA8［J］.J Biochem,2022,170(6):689-698.
[14] 刘亮，朱正权，阿满·哈迪尔别克，等.DNA甲基化对miR-133a表达及胶质瘤细胞增殖及凋亡的影响［J］.现代肿瘤医学，2021,29（08）：1296-1300. LIU Liang,ZHU Zhengquan,Aman·Hadierbieke,et al.Effect of DNA methylation on the expression of microRNA-133a and the proliferation and apoptosis of glioma cells［J］.Modern Oncology,2021,29（08）：1296-1300.
[15] LUO Y,ZHENG S,WU Q,et al.Long noncoding RNA (lncRNA) EIF3J-DT induces chemoresistance of gastric cancer via autophagy activation［J］.Autophagy,2021,17(12):4083-4101.
[16]YANG Y,JIANG C,YANG Y,et al.Silencing of LncRNA-HOTAIR decreases drug resistance of non-small cell lung cancer cells by inactivating autophagy via suppressing the phosphorylation of ULK1［J］.Biochem Biophys Res Commun,2018,497(4):1003-1010.
[17] ROSAS-ALONSO R,COLMENAREJO-FERNANDEZ J,PERNIA O,et al.Clinical validation of a novel quantitative assay for the detection of MGMT methylation in glioblastoma patients［J］.Clin Epigenetics,2021,13(1):52-65.
[18]朱鸣峰.MGMT基因在脑胶质瘤组织中表达变化,突变及功能的生物信息学分析［J］.山东医药,2020,60(14):25-27. ZHU MF.Bioinformatics analysis of MGMT gene expression,mutation and biological function in gliomas［J］.Shandong Medical Journal,2020,60(14):25-27.
[19]袁洁,张珏,费智敏.脑瘤一号方联合替莫唑胺对裸鼠脑胶质瘤模型MGMT、Bax和Bcl-2蛋白表达的影响［J］.中国中西医结合杂志,2019,39(12):1477-1482. YUAN J,ZHANG J,FEI ZM.Effects of Naoliu Decoction Ⅰ combined with temozolomide on expression of MGMT,Bax and Bcl-2 Pro-teins in glioma nude mice［J］.Chinese Journal of Integrated Traditional and Western Medicine,2019,39(12):1477-1482.

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湖北省武汉市医学科研项目（编号：WX21C05）
Last Update: 1900-01-01