Significant decrease of a master regulator of genes (REST/NRSF) in high-grade squamous intraepithelial lesion and cervical cancer

Cortés-Sarabia, Karen; Alarcón‐Romero, Luz del Carmen; Flores‐Alfaro, Eugenia; Illades‐Aguiar, Berenice; Vences-Velázquez, Amalia; Mendoza-Catalán, Miguel Ángel; Navarro-Tito, Napoleón; Valdés, Jesús; Moreno‐Godínez, Ma. Elena; Ortuño-Pineda, Carlos

doi:10.1016/j.bj.2020.08.012

Cited by 3 publications

(5 citation statements)

References 42 publications

(54 reference statements)

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“…In addition to the evidence showing a consistent association between REST diminution and neural trait acquisition, we found a significant reduction in nuclear REST in cytology samples of premalignant lesions and cervical cancers from an extensive group of patients [ 16 ]. These findings suggest a potential effect of REST diminution on the transcriptome and re-expression of neural genes.…”

Section: Resultsmentioning

confidence: 62%

“…Some examples of cancers with reduced expression levels of REST include lung [ 10 ], breast [ 11 ], prostate [ 12 ], and skin cancers [ 20 ]. The nuclear REST diminution recently found in premalignant lesions and cervical cancers with high-risk human papillomaviruses appears to be a promising diagnosis tool [ 16 ]. However, the expression of REST at several stages of cervical carcinogenesis and the effect of REST diminution on the transcription of neuronal genes have not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

“…As a result, the search for new biomarkers with diagnostic and prognostic value for cervical cancer has become an area of great interest. We previously reported that REST is reduced in human samples diagnosed with squamous intraepithelial lesions (SILs) and invasive cervical squamous cell carcinoma (SCC) of the cervix with high-risk human papillomavirus [ 16 ]. However, the impact of REST diminution on the transcription of its neural targets in CC is unknown.…”

Section: Introductionmentioning

confidence: 99%

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REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer

et al. 2023

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Background and Objectives: REST (RE1-silencing transcription factor) diminution is associated with transcriptional relaxation, neuropeptide overexpression, and phenotype redefinition in neuroendocrine cancers, but this effect has barely been studied in cervical cancer (CC). We previously reported reduced expressions of REST in samples with premalignant lesions and CC; however, the transcriptional consequences for neural genes associated with reduced REST expression in CC are unknown. Therefore, the objective of this work was to evaluate the expression of neuronal genes in cancerous cells with reduced expression levels of REST. Materials and Methods: Here, we monitored levels of REST by immunostaining along the premalignant lesions and in invasive cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma (ADC) in tissue samples from female patients from southern Mexico and the derivative cell lines SiHa and HeLa, respectively. Next, we selected REST target genes in silico and explored the effect of REST silencing by RT-PCR in siRNA-treated HeLa cells. Results: The results show a REST diminution in premalignant lesions, SCC, ADC, and cancerous cell lines. Further REST silencing in HeLa cells altered the expression of genes containing the RE1 (Restrictive Element 1) sequence, including CgA (chromogranin A), CHRNβ2 (cholinergic receptor nicotinic β 2 subunit), BDNF (brain-derived neurotrophic factor), CRF (corticotropin-releasing factor), and RASSF1A (Ras association domain family 1). Conclusions: This work provides preliminary evidence of the role of REST loss in the transcriptional regulation of its target genes in HeLa cells, which could have positive implications for the search for new biomarkers of cervical cancer.

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Section: Resultsmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer

et al. 2023

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“…As expected, this transcriptional induction was not observed for testis-specific CT genes. Downregulated expression of REST has been previously reported in several types of non-neuronal human tumors (40,41). We therefore examined if ectopic activation of CB and CBT genes in tumor cells correlated with REST downregulation.…”

Section: The Rest Repressor Is Involved In the Regulation Of A Subset...mentioning

confidence: 94%

An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

Diacofotaki,

Loriot,

De Smet

2023

Preprint

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Tumoral transformation processes sometimes include activation of unscheduled gene expression programs in the cancer cells. This is best exemplified by the so-called cancer-testis (CT) genes, a group of genes expressed in testicular germ cells that become activated in tumors of various somatic origins, through a process of DNA demethylation. Here, we explored the possibility that other tissue-specific gene clusters may become ectopically activated in tumors. Lung adenocarcinoma (LUAD) was used as a model, as all necessary transcriptomic datasets were available, including that of AT2 cells, the cell-of-origin of LUAD. We found that besides CT genes, an abundant group of genes expressed in the brain (CB genes, n=63) or in both brain and testis (CBT genes, n=28) become aberrantly activated in LUAD cell lines and tissues. Interestingly, activation of CB and CBT gene clusters was also detected in various other tumor types. Most CB/CBT genes appeared to exert neuronal functions. Moreover, a significant number of them encode antigens involved in neurological paraneoplastic syndromes. Neither neuroendocrine transdifferentiation, which occurs in 10-20% LUAD, nor DNA demethylation appeared to be responsible of the ectopic activation of CB and CBT gene clusters. Instead, prediction tools and depletion experiments identified the REST repressor as a regulator of a number of CB/CBT genes. Conclusion: Together, our data indicate that tumor development is associated with aberrant activation of a brain gene expression program, supporting the assumption that acquisition of neuronal functions might contribute to malignancy.

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“…The team found altered expression of the gene expression regulator REST and tumor suppressor gene RASSF1A in squamous cell carcinoma (SCC) and squamous intraepithelial (SIL) lesions. Monitoring expression levels of REST and RASSF1A were hence proposed to be useful for SIL and SCC prognosis [ 15 ].…”

Section: Spotlightmentioning

confidence: 99%

The best protection is early detection

Kattner¹

2021

Biomedical Journal

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Significant decrease of a master regulator of genes (REST/NRSF) in high-grade squamous intraepithelial lesion and cervical cancer

Cited by 3 publications

References 42 publications

REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer

REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer

An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma

The best protection is early detection

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