Minichromosome maintenance protein family member 6 mediates hepatocellular carcinoma progression by recruiting UBE3A to induce P53 ubiquitination

Zhang, Xue; Bian, Saiyan; Ni, Yicheng; Zhou, Lei; Yang, Chenyu; Zhang, Chenfeng; Sun, Xinchen; Xu, Nuo; Xu, Shiyu; Wang, Yilang; Gu, Shudong; Zheng, Wenjie

doi:10.1016/j.ijbiomac.2023.125854

Cited by 2 publications

(1 citation statement)

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“…Conversely, the knockdown of MCM6 suppresses cell proliferation, migration, and organoid expansion [ 28 ]. In addition, MCM6 recruits ubiquitin ligase E3A ( UBE3A ) to enhance the ubiquitination and degradation of the p53 protein, which can facilitate the aggressiveness of cells [ 29 ]. MCM10 dysfunction leads to telomerase shortening by accumulating aberrant replication forks enriched with single-stranded DNA [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Glutamine Regulates Gene Expression Profiles to Increase the Proliferation of Porcine Intestinal Epithelial Cells and the Expansion of Intestinal Stem Cells

Zhu,

Lai,

Yao

et al. 2023

Animals

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The intestinal epithelium is known for its rapid self-renewal, and glutamine is crucial in providing carbon and nitrogen for biosynthesis. However, understanding how glutamine affects gene expression in the intestinal epithelium is limited, and identifying the essential genes and signals involved in regulating intestinal epithelial cell growth is particularly challenging. In this study, glutamine supplementation exhibited a robust acceleration of intestinal epithelial cell proliferation and stem cell expansion. RNA sequencing indicated diverse transcriptome changes between the control and glutamine supplementation groups, identifying 925 up-regulated and 1152 down-regulated genes. The up-regulated DEGs were enriched in the KEGG pathway of cell cycle and GO terms of DNA replication initiation, regulation of phosphatidylinositol 3-kinase activity, DNA replication, minichromosome maintenance protein (MCM) complex, and ATP binding, whereas the down-regulated DEGs were enriched in the KEGG pathway of p53 signaling pathway, TNF signaling pathway, and JAK-STAT signaling pathway and GO terms of inflammatory response and intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress. Furthermore, GSEA analysis revealed a significant up-regulation of the cell cycle, DNA replication initiation, ATP-dependent RNA helicase activity, and down-regulation of the TNF signaling pathway. The protein–protein association network of the intersecting genes highlighted the significance of DNA replication licensing factors (MCM3, MCM6, and MCM10) in promoting intestinal epithelial growth in response to glutamine. Based on these findings, we propose that glutamine may upregulate DNA replication licensing factors, leading to increased PI3K/Akt signaling and the suppression of TNF, JAK-STAT, and p53 pathways. Consequently, this mechanism results in the proliferation of porcine intestinal epithelial cells and the expansion of intestinal stem cells.

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Section: Discussionmentioning

confidence: 99%