Correlations of miR-432 expression with cell proliferation and migration and tripartite motif containing protein 38 expression in isocitrate dehydrogenase wild-type glioma, and overall survival of these patients
10.3760/cma.j.cn115354-20200403-00247
- VernacularTitle:miR-432与 IDH野生型胶质瘤的细胞增殖迁移、患者总生存期及 TRIM38基因表达的关系
- Author:
Yu DONG
1
;
Nan LU
;
Yuhe LIU
;
An'an YIN
Author Information
1. 西北大学附属医院 西安市第三医院口腔科 710018
- Keywords:
Glioma;
Micro RNA-432;
Isocitrate dehydrogenase;
Tripartite motif containing protein 38
- From:
Chinese Journal of Neuromedicine
2021;20(2):126-132
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the correlations of micro RNA (miR)-432 expression with cell proliferation and migration, and tripartite motif containing protein 38 ( TRIM38) gene expression in isocitrate dehydrogenase ( IDH) wild-type glioma, and overall survival (OS) of these patients. Methods:(1) The miRNA expression microarray data of 198 glioma patients (81 with IDH mutant, 106 with IDH wild type and 11 with unknown type) and 5 nontumorous brain tissues (controls) were downloaded from China Glioma Genome Atlas (CGGA); expression differences of miR-432 between IDH mutant and IDH wild type glioma subgroups and normal controls were compared. According to the median value of miR-432 expression in IDH wild-type glioma samples, these patients were divided into miR-432 high expression group ( n=51) and miR-432 low expression group ( n=53), Kaplan-Meier survival analysis was used to compare the OS, univariate and multivariate Cox regression analyses were used to determine the factors influencing OS, and Pearson correlation was used to analyze the relation between miR-432 expression and TRIM38 gene expression. (2) Human glioma cell line U251 was routinely cultured and divided into nonsense sequence control group and miR-432 mimics group; CCK-8 assay was used to detect the cell viability on the 1 st-5 th d of cultivation; Transwell assay was used to detect the cell migration; quantitative reverse transcription PCR (RT-qPCR) was used to detect the TRIM38 mRNA expression. (3) According to the binding sites between miR-432 and TRIM38 gene predicted by miRNA target gene prediction database, the wild-type TRIM38 3'-terminal untranslated region (3'-UTR) and mutant TRIM38 3'-UTR sequences were designed; U251 cells were divided into miR-432 nonsense sequence+wild-type TRIM38 3'-UTR group, miR-432 mimics+wild-type TRIM38 3'-UTR group, miR-432 nonsense sequence+mutant TRIM38 3'-UTR group, and miR-432 mimics+mutant TRIM38 3'-UTR group; the luciferase activity in these 4 groups was detected by microplate assay. Results:(1) The miR-432 expression in IDH wild-type glioma was significantly decreased as compared with that in the IDH mutant one ( P<0.05). The OS of patients in the miR-432 low-expression group was significantly shorter as compared with that in the miR-432 high-expression group ( P<0.05). Age, glioma grading, and miR-432 expression were significantly correlated with OS of IDH wild-type glioma patients ( P<0.05), but miR-432 expression level was not an independent influencing factor for OS ( P>0.05). The miR-432 and TRIM38 mRNA expressions in IDH wild-type glioma samples were negatively correlated ( r=-0.255, P=0.018). (2) As compared with nonsense sequence control group, miR-432 mimics group had significantly lower cell activity on the 2 rd-5 th d of cultivation, significantly smaller number of migrated cells, and statistically decreased TRIM38 mRNA expression ( P<0.05). (3) The luciferase activity of cells in the miR-432 mimics+wild-type TRIM38 3'-UTR group was significantly lower than that in the miR-432 nonsense+wild-type TRIM38 3'-UTR group ( P<0.05). Conclusion:The miR-432 expression is low in IDH wild-type glioma tissues, and it is associated with poor prognosis of these patients; miR-432 overexpression can inhibit the proliferation and migration of glioma cells, which may be related to its specific binding of TRIM38 gene and interference the expression of this gene.
