REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer
<i>Background and Objectives:</i> 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 pre...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/3/537 |
| _version_ | 1797610260714749952 |
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| author | Karen Cortés-Sarabia Luz Del Carmen Alarcón-Romero Miguel Ángel Mendoza-Catalán Juan Carlos Carpio-Pedroza Eduardo Castañeda-Saucedo Carlos Ortuño-Pineda |
| author_facet | Karen Cortés-Sarabia Luz Del Carmen Alarcón-Romero Miguel Ángel Mendoza-Catalán Juan Carlos Carpio-Pedroza Eduardo Castañeda-Saucedo Carlos Ortuño-Pineda |
| author_sort | Karen Cortés-Sarabia |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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). <i>Conclusions</i>: 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. |
| first_indexed | 2024-03-11T06:12:27Z |
| format | Article |
| id | doaj.art-97e9d610d36c4cc6bd1deb218f936c55 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T06:12:27Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-97e9d610d36c4cc6bd1deb218f936c552023-11-17T12:32:03ZengMDPI AGMedicina1010-660X1648-91442023-03-0159353710.3390/medicina59030537REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical CancerKaren Cortés-Sarabia0Luz Del Carmen Alarcón-Romero1Miguel Ángel Mendoza-Catalán2Juan Carlos Carpio-Pedroza3Eduardo Castañeda-Saucedo4Carlos Ortuño-Pineda5Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo 39090, MexicoFacultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo 39090, MexicoFacultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo 39090, MexicoDepartamento de Parasitología, Instituto de Diagnóstico y Referencia Epidemiológicos “Dr. Manuel Martínez Báez”, Francisco de P. Miranda 177, Mexico City 01480, MexicoFacultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo 39090, MexicoFacultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas s/n, Chilpancingo 39090, Mexico<i>Background and Objectives:</i> 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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). <i>Conclusions</i>: 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.https://www.mdpi.com/1648-9144/59/3/537neural phenotypeREST targetstranscriptional regulationHeLa cellscervical intraepithelial neoplasia |
| spellingShingle | Karen Cortés-Sarabia Luz Del Carmen Alarcón-Romero Miguel Ángel Mendoza-Catalán Juan Carlos Carpio-Pedroza Eduardo Castañeda-Saucedo Carlos Ortuño-Pineda REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer Medicina neural phenotype REST targets transcriptional regulation HeLa cells cervical intraepithelial neoplasia |
| title | REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer |
| title_full | REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer |
| title_fullStr | REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer |
| title_full_unstemmed | REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer |
| title_short | REST/NRSF Silencing Modifies Neuronal Gene Expression in siRNA-Treated HeLa Cells: A Preliminary Exploration in the Search for Neuronal Biomarkers of Cervical Cancer |
| title_sort | rest nrsf silencing modifies neuronal gene expression in sirna treated hela cells a preliminary exploration in the search for neuronal biomarkers of cervical cancer |
| topic | neural phenotype REST targets transcriptional regulation HeLa cells cervical intraepithelial neoplasia |
| url | https://www.mdpi.com/1648-9144/59/3/537 |
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