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Dysregulation of Transcription Factor Networks Unveils Different Pathways in Human Papillomavirus 16-Positive Squamous Cell Carcinoma and Adenocarcinoma of the Uterine Cervix

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the most common
histological types of cervical cancer (CC). The worse prognosis of ADC cases highlights
the need for better molecular characterization regarding differences between these
CC types. RNA-Seq analysis of seven SCC and three ADC human papillomavirus
16-positive samples and the comparison with public data from non-tumoral human
papillomavirus-negative cervical tissue samples revealed pathways exclusive to each
histological type, such as the epithelial maintenance in SCC and the maturity-onset
diabetes of the young (MODY) pathway in ADC. The transcriptional regulatory network
analysis of cervical SCC samples unveiled a set of six transcription factor (TF) genes
with the potential to positively regulate long non-coding RNA genes DSG1-AS1,
CALML3-AS1, IGFL2-AS1, and TINCR. Additional analysis revealed a set of MODY TFs
regulated in the sequence predicted to be repressed bymiR-96-5p ormiR-28-3p in ADC.
These microRNAs were previously described to target LINC02381, which was predicted
to be positively regulated by two MODY TFs upregulated in cervical ADC. Therefore, we
hypothesize LINC02381might act by decreasing the levels ofmiR-96-5p andmiR-28-3p,
promoting the MODY activation in cervical ADC. The novel TF networks here described
should be explored for the development of more efficient diagnostic tools.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84355
Date28 March 2023
CreatorsBispo, Saloe, Farias, Ticiana D., de Araujo-Souza, Patricia Savio, Cintra, Ricardo, dos Santos, Hellen Geremias, Jorge, Natasha Andressa Nogueira, Castro, Mauro Antônio Alves, Wajnberg, Gabriel, de Miranda Scherer, Nicole, Genta, Maria Luiza Nogueira Dias, Carvalho, Jesus Paula, Villa, Luisa Lina, Sichero, Laura, Passetti, Fabio
PublisherFrontiers Research Foundation
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish, German
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation2234-943X, 626187

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