CBX7 is Dualistic in Cancer Progression Based on its Function and Molecular Interactions

Li, Jun; Ouyang, Taohui; Li, Meihua; Hong, Tao; Wang, Meng; Zhang, Na

doi:10.3389/fgene.2021.740794

Cited by 13 publications

(8 citation statements)

References 84 publications

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“…Interestingly, a recent study revealed a distinct role of two isoforms of CBX7 (p36 CBX7 and p22 CBX7 ) in cell proliferation [39]. In particular, p22 CBX7 potentially interacts with cell cycle regulators [40]. We found that low expression of CBX7 increases genome instability, suggesting that its loss may lead to misregulation of the cell cycle and subsequently cause chromosomal instability.…”

Section: Discussionmentioning

confidence: 61%

Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

Cai¹,

Chang²,

Pérez-Losada³

et al. 2023

Oncol Insights

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CBX7 is a member of the chromobox gene family, which plays an important role in epigenetic transcriptional regulation. In this study, we found that compared to normal mammary tissues, mRNA levels of CBX7 are consistently significantly downregulated in breast cancers (BCs) across different datasets. Integrative multiomics analysis revealed the genetic and epigenetic mechanisms for the loss of CBX7 expression in BCs. Lower expression levels of CBX7 are significantly associated with shorter overall, disease-free, and distant metastasis-free survival of patients with BC. These prognostic impacts of CBX7 are independent of estrogen receptor status and PAM50 molecular subtypes. Coexpression analysis identified 207 genes consistently coexpressed with CBX7 (157 negatively and 50 positively). Gene Ontology, KEGG, and Reactome enrichment analysis revealed that cell cycle‑, DNA replication‑, and mitosis-related pathways are significantly overrepresented within the set of CBX7 negatively coexpressed genes, suggesting that CBX7 functions as a suppressor of the cell cycle. Moreover, transcription factor enrichment analysis detected the E2F family of transcription factors significantly associated with CBX7 negatively coexpressed genes, consistent with E2F function regulating the cell cycle. Furthermore, we found that loss of CBX7 expression significantly increases genomic instability and tumor mutation burden. Our findings indicate that CBX7 acts as a tumor suppressor in BC through its potential role in the negative regulation of cell proliferation and the maintenance of genome integrity.

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Section: Discussionmentioning

confidence: 61%

Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

Cai¹,

Chang²,

Pérez-Losada³

et al. 2023

Oncol Insights

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“…The Wnt signaling pathway has been shown to be critical for IEC proliferation and renewal of intestinal epithelial stem cells, and mutations in this pathway are strongly associated with colon cancer. Importantly, among the 35 significantly upregulated miR-181 –predicted targets in DKO IECs during DSS-induced colitis, we also found five additional putative inhibitors of the Wnt signaling pathway ( Cbx7 , Sox6 , Nr1h4 , Setd7 , and Dgkq ; Kim et al, 2015 ; Li et al, 2021 ; Pei et al, 2020 ; Leow et al, 2016 ; Yu et al, 2020 ; Shen et al, 2015 ; Jacob et al, 2011 ). While upregulation of some miR-181 –predicted targets can be the consequence of enhanced colon inflammation, these results also suggest that the miR-181 family could directly promote the activation of the Wnt signaling pathway during DSS-induced colitis to enhance IEC proliferation and repair.…”

Section: Resultsmentioning

confidence: 75%

The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium

Jimenez

Clark

Wright

et al. 2022

Journal of Experimental Medicine

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The intestinal epithelium is a key physical interface that integrates dietary and microbial signals to regulate nutrient uptake and mucosal immune cell function. The transcriptional programs that regulate intestinal epithelial cell (IEC) quiescence, proliferation, and differentiation have been well characterized. However, how gene expression networks critical for IECs are posttranscriptionally regulated during homeostasis or inflammatory disease remains poorly understood. Herein, we show that a conserved family of microRNAs, miR-181, is significantly downregulated in IECs from patients with inflammatory bowel disease and mice with chemical-induced colitis. Strikingly, we showed that miR-181 expression within IECs, but not the hematopoietic system, is required for protection against severe colonic inflammation in response to epithelial injury in mice. Mechanistically, we showed that miR-181 expression increases the proliferative capacity of IECs, likely through the regulation of Wnt signaling, independently of the gut microbiota composition. As epithelial reconstitution is crucial to restore intestinal homeostasis after injury, the miR-181 family represents a potential therapeutic target against severe intestinal inflammation.

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“…The role of CBX7 expression in tumours is not clear. It has been linked to inhibition of primary tumour progression in vivo once tumours were already established, but also plays an oncogenic role in some cancers [ 51 , 52 ]. Thus, we examined whether increased stable expression of CBX7 by rAAV with piggyBac transposase-mediated somatic integration in established primary WT tumour cells could inhibit tumour progression in vivo.…”

Section: Resultsmentioning

confidence: 99%

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

Chen

Zhao

Zhang

et al. 2022

Cell. Mol. Life Sci.

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MiR-181 expression levels increased in hepatocellular carcinoma (HCC) compared to non-cancerous tissues. MiR-181 has been widely reported as a possible driver of tumourigenesis but also acts as a tumour suppressor. In addition, the miR-181 family regulates the development and function of immune and vascular cells, which play vital roles in the progression of tumours. More complicatedly, many genes have been identified as miR-181 targets to mediate the effects of miR-181. However, the role of miR-181 in the development of primary tumours remains largely unexplored. We aimed to examine the function of miR-181 and its vital mediators in the progression of diethylnitrosamine-induced primary liver cancers in mice. The size of liver tumours was significantly reduced by 90% in global (GKO) or liver-specific (LKO) 181ab1 knockout mice but not in hematopoietic and endothelial lineage-specific knockout mice, compared to WT mice. In addition, the number of tumours was significantly reduced by 50% in GKO mice. Whole-genome RNA-seq analysis and immunohistochemistry showed that epithelial-mesenchymal transition was partially reversed in GKO tumours compared to WT tumours. The expression of CBX7, a confirmed miR-181 target, was up-regulated in GKO compared to WT tumours. Stable CBX7 expression was achieved with an AAV/Transposase Hybrid-Vector System and up-regulated CBX7 expression inhibited liver tumour progression in WT mice. Hepatic CBX7 deletion restored the progression of LKO liver tumours. MiR-181a expression was the lowest and CBX7 expression the highest in iClust2 and 3 subclasses of human HCC compared to iClust1. Gene expression profiles of GKO tumours overlapped with low-proliferative peri-portal-type HCCs. Liver-specific loss of miR-181ab1 inhibited primary liver tumour progression via up-regulating CBX7 expression, but tumour induction requires both hepatic and non-hepatic miR-181. Also, miR-181ab1-deficient liver tumours may resemble low-proliferative periportal-type human HCC. Graphical abstract

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CBX7 is Dualistic in Cancer Progression Based on its Function and Molecular Interactions

Cited by 13 publications

References 84 publications

Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

The miR-181 family regulates colonic inflammation through its activity in the intestinal epithelium

Liver-specific deletion of miR-181ab1 reduces liver tumour progression via upregulation of CBX7

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