Abnormal Gene Expression Regulation Mechanism of Myeloid Cell Nuclear Differentiation Antigen in Lung Adenocarcinoma

被引:13
|
作者
Tang, Zhongxiang [1 ,2 ]
Wang, Lili [1 ,2 ]
Bajinka, Ousman [1 ,2 ]
Wu, Guojun [1 ,2 ]
Tan, Yurong [1 ,2 ]
机构
[1] Cent South Univ, Sch Basic Med Sci, Dept Med Microbiol, Changsha 410078, Peoples R China
[2] Cent South Univ, China Africa Res Ctr Infect Dis, Sch Basic Med Sci, Changsha 410078, Hunan, Peoples R China
来源
BIOLOGY-BASEL | 2022年 / 11卷 / 07期
关键词
lung adenocarcinoma; myeloid cell nuclear differentiation antigen; gene methylation; SPI1; miRNA; TUMOR-SUPPRESSOR; CANCER; METHYLATION; PROTEIN;
D O I
10.3390/biology11071047
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Simple Summary Lung adenocarcinoma is the main pathological type of lung cancer with a very low 5-year survival rate. In the present study, through analyzing the mRNA, miRNA, and DNA methylation sequencing data from TCGA, combined with the downloaded clinical data, we accidentally found that both methylation and gene expression of some genes were up-regulated or down-regulated, which is in contradiction with our general understanding. To probe the mechanism, we selected MNDA associated with lung cancer prognosis for further analysis. The results showed that the imbalance of methylase and demethylase resulted in the demethylation of MNDA. Moreover, the expression of SPI1, the main transcription factor of MNDA, was down-regulated, while the two miRNAs hsa-miR-33a-5p and hsa-miR-33b-5p, which directly targeted MNDA, were up-regulated, thus inhibiting the expression of MNDA. In conclusion, the abnormal expression of MNDA in lung cancer is the result of the combined effects of transcriptional and post-transcriptional regulation. Lung adenocarcinoma (LA) is the main pathological type of lung cancer with a very low 5-year survival rate. In the present study, after downloading the mRNA, miRNA, and DNA methylation sequencing data from TCGA, combined with the downloaded clinical data, comparative analysis, prognostic analysis, GO and KEGG analysis, GSEA analysis, methylation analysis, transcriptional regulation and post-transcriptional regulation were performed. We found that both methylation and gene expression of MNDA in LA were down-regulated, while high expression of MNDA was associated with good overall survival in LA. To probe the mechanism, further analysis showed that SPI1 was the main transcription factor of MNDA, but it was also down-regulated in LA. At the same time, the expression of eight target miRNAs of MNDA was significantly up-regulated, and the expression of hsa-miR-33a-5p and hsa-miR-33b-5p were verified to directly target MNDA. In conclusion, the abnormal expression of MNDA in LA is the result of the combined effects of transcriptional and post-transcriptional regulation.
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页数:17
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