Effect of lysine demethylase 5C on renal carcinoma metastasis

doi:10.3969/j.issn.1674-8115.2023.05.007

Abstract

Abstract:

Objective ·To investigate the effects of lysine demethylase 5C (KDM5C) on the migration and invasion of renal clear cell carcinoma, analyze the genes regulated by KDM5C and explore the mechanisms of promoting renal cell carcinoma after its inactivation. Methods ·Lentivirus was used to construct human renal clear cell carcinoma 786-O and Caki-1 cell lines with KDM5C stable knockout. The changes of migration and invasion abilities of renal carcinoma cells were observed by Transwell assay. Epithelial-mesenchymal transition (EMT) protein expression was detected by Western blotting. Differential gene analysis and functional pathway enrichment analysis were performed by using 786-O Control-sg, KDM5C-sg 2 group cell RNA sequencing data and The Cancer Genome Atlas (TCGA) public database to further explore the cancer-promoting mechanisms after KDM5C deletion. The up-regulated EMT-related genes in sequencing data were screened out according to the EMT gene set, and the genes were screened by survival analysis and univariate COX analysis. Finally, LASSO regression analysis and risk forest model were used to further screen genes highly related to the phenotype after KDM5C knockout. Results ·After the deletion of KDM5C, both 786-O and Caki-1 cells showed significant migration and invasion phenotypes compared with control groups. Analysis of TCGA database indicated that mutation of KDM5C in renal cancer patients led to poor prognosis (P=0.042). RNA sequencing analysis showed that KDM5C knockout may affect cell adhesion molecules and upregulate epithelial-mesenchymal transition-related genes. Western blotting detected the increased expression levels of β-catenin, Vimentin and Snail proteins in two kinds of cells after KDM5C knockout. Finally, ten up-regulated EMT genes were obtained by survival analysis and univariate COX analysis for LASSO regression analysis and risk forest model prediction. The results showed that KDM5C may have a regulatory effect on PLAUR gene. Conclusion ·The mutation of KDM5C can promote the development of renal carcinoma by enhancing migration and invasion.

Key words: lysine demethylase 5C (KDM5C), renal clear cell carcinoma, migration, epithelial-mesenchymal transition

CLC Number:

R737.11

CHEN Ningdai, ZHOU Bingqian, CHEN Zheyi, CHEN Shiyu, ZHEN Yingxia. Effect of lysine demethylase 5C on renal carcinoma metastasis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(5): 571-579.

Figures/Tables 5

Fig 1 Expression of KDM5C in various cancer cells

Fig 2 Effect of KDM5C knockout on renal clear cell carcinoma cell

Fig 3 RNA sequencing analysis of renal carcinoma cells with KDM5C knockout

Fig 4 Effects of KDM5C knockout on EMT-related proteins expression

Fig 5 Effect of up-regulated EMT-related gene on prognosis after KDM5C knockout

TrendMD

References 19

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