Sex-Dependent Regulation of Estrogen Receptor β in Human Colorectal Cancer Tissue and its Relationship With Clock Genes and VEGF-A Expression

Herichová, Iveta; Reis, Richard M.; Hasakova, Kristina; Vician, M; Zeman, Michal

doi:10.33549/physiolres.934352

Cited by 7 publications

(3 citation statements)

References 40 publications

(31 reference statements)

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“…Moreover, EGFR and VEGF can be detected in CRC patients using fluorescence-Raman endoscopy [ 140 ]. In addition, VEGF-A expression in CRC tissue is associated with worse survival rate in male compared with females [ 141 ].…”

Section: Crc Pathogenesismentioning

confidence: 99%

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Ştefani¹,

Miricescu

Stănescu-Spînu

et al. 2021

IJMS

155

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Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC.

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Section: Crc Pathogenesismentioning

confidence: 99%

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Ştefani¹,

Miricescu

Stănescu-Spînu

et al. 2021

IJMS

155

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show abstract

“…The presence of functional ESR2 [18] or ESR2 overexpression [20] was also shown to inhibit CRC progression under in vivo conditions in mammals. Protective effects of E2 are, to some extent, lost in CRC tissue as expression of ESR2 is substantially lower in tumours compared to adjacent tissues [106,107].…”

Section: Plos Onementioning

confidence: 99%

Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation

Moravčík,

Olejárová,

Zlacká

et al. 2023

PLoS ONE

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The small non-coding RNA miR-34a is a p53-regulated miRNA that acts as a tumour suppressor of colorectal cancer (CRC). Oncogenesis is also negatively influenced by deregulation of the circadian system in many types of tumours with various genetic backgrounds. As the clock gene per2 was recently recognized as one of the target genes of miR-34a, we focused on the miR-34a-mediated influence on the circadian oscillator in CRC cell lines DLD1 and LoVo, which differ in their p53 status. Previously, a sex-dependent association between the expression of per2 and that of miR-34a was demonstrated in CRC patients. Therefore, we also investigated the effect of 17β-estradiol (E2) on miR-34a oncostatic functions. miR-34a mimic caused a pronounced inhibition of per2 expression in both cell lines. Moreover, miR-34a mimic significantly inhibited bmal1 expression in LoVo and rev-erbα expression in DLD1 cells and induced clock gene expression in both cell lines. miR-34a mimic caused a pronounced decrease in sirt1 and cyclin D1 expression, which may be related to the inhibition of proliferation observed after mir-34a administration in DLD1 cells. E2 administration inhibited the migration and proliferation of DLD1 cells. E2 and miR-34a, when administered simultaneously, did not potentiate each other’s effects. To conclude, miR-34a strongly influences the expression of components of the circadian oscillator without respect to p53 status and exerts its oncostatic effects via inhibition of sirt1 and cyclin D1 mRNA expression. E2 administration inhibits the growth of DLD1 cells; however, this effect seems to be independent of miR-34a-mediated action. With respect to the possible use of miR-34a in cancer treatment, clock genes can be considered as off-target genes, as changes in their expression induced by miR-34a treatment do not contribute to the oncostatic functions of miR-34a. Possible ambiguous oncogenic characteristics should be taken into consideration in future clinical studies focused on miR-34a.

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“…Moreover, the loss of ERβ is associated with enhanced CRC proliferation potential [121], leading to the hypothesis that high ERβ expression may not only be protective against developing CRC but also a prognostic marker and molecular target in the treatment of colon cancer [122,123]. Indeed, a predominant expression of ERβ may show sexual differentiation for its protective role in the early stages of CRC [124].…”

Section: Oestrogen Signalling Via Erα and Erβ In Colon Cancermentioning

confidence: 99%

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

Harvey,

Harvey

2023

Genes

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Colon cancer (CRC) is a prevalent malignancy that exhibits distinct differences in incidence, prognosis, and treatment responses between males and females. These disparities have long been attributed to hormonal differences, particularly the influence of oestrogen signalling. This review aims to provide a comprehensive analysis of recent advances in our understanding of the molecular mechanisms underlying sex differences in colon cancer and the protective role of membrane and nuclear oestrogen signalling in CRC development, progression, and therapeutic interventions. We discuss the epidemiological and molecular evidence supporting sex differences in colon cancer, followed by an exploration of the impact of oestrogen in CRC through various genomic and nongenomic signalling pathways involving membrane and nuclear oestrogen receptors. Furthermore, we examine the interplay between oestrogen receptors and other signalling pathways, in particular the Wnt/β-catenin proliferative pathway and hypoxia in shaping biological sex differences and oestrogen protective actions in colon cancer. Lastly, we highlight the potential therapeutic implications of targeting oestrogen signalling in the management of colon cancer and propose future research directions to address the current gaps in our understanding of this complex phenomenon.

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Sex-Dependent Regulation of Estrogen Receptor β in Human Colorectal Cancer Tissue and its Relationship With Clock Genes and VEGF-A Expression

Cited by 7 publications

References 40 publications

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation

Sex Differences in Colon Cancer: Genomic and Nongenomic Signalling of Oestrogen

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