FAM83H-AS1 is a potential modulator of cancer driver genes across different tumors and a prognostic marker for ER/PR + BRCA patients

Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogenic disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a...

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Published in:Scientific reports 2020-08, Vol.10 (1), p.14145-14145, Article 14145
Main Authors: Ríos-Romero, Magdalena, Cedro-Tanda, Alberto, Peña-Luna, Mónica, Mancera-Rodríguez, Marco Antonio, Hidalgo-Pérez, Lizbett, Cisneros-Villanueva, Mireya, Beltrán-Anaya, Fredy Omar, Arellano-Llamas, Rocío, Jiménez-Morales, Silvia, Alfaro-Ruíz, Luis Alberto, Tenorio-Torres, Alberto, Domínguez-Reyes, Carlos, Villegas-Carlos, Felipe, Ochoa-Mendoza, Elsa, Hidalgo-Miranda, Alfredo
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Breast Neoplasms - therapy
Cell adhesion & migration
Cell death
Cell migration
Cell Movement - genetics
Claudin-1 - genetics
Correlation analysis
Drug Resistance, Neoplasm - genetics
Estrogen receptors
Female
Gene expression
Gene Expression Regulation, Neoplastic - genetics
Humans
Middle Aged
Progesterone
Prognosis
Proteins - genetics
Proteins - metabolism
Public health
Receptors, Estrogen - metabolism
Receptors, Progesterone - metabolism
Survival Analysis
Tamoxifen
Tamoxifen - therapeutic use
Transcription Factors - genetics
Tumor Suppressor Proteins - genetics
Tumors
Young Adult
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Summary:Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. BRCA is a molecularly heterogenic disease, particularly at gene expression (mRNAs) level. Recent evidence shows that coding RNAs represent only 34% of the total transcriptome in a human cell. The rest of the 66% of RNAs are non-coding, so we might be missing relevant biological, clinical or regulatory information. In this report, we identified nine novel tumor types from TCGA with FAM83H-AS1 deregulation. We used survival analysis to demonstrate that FAM83H-AS1 expression is a marker for poor survival in IHC-detected ER and PR positive BRCA patients and found a significant correlation between FAM83H-AS1 overexpression and tamoxifen resistance. Estrogen and Progesterone receptor expression levels interact with FAM83H-AS1 to potentiate its effect in OS prediction. FAM83H-AS1 silencing impairs two important breast cancer related pathways: cell migration and cell death. Among the most relevant potential FAM83H-AS1 gene targets, we found p63 and claudin 1 (CLDN1) to be deregulated after FAM83H-AS1 knockdown. Using correlation analysis, we show that FAM83H-AS1 can regulate a plethora of cancer-related genes across multiple tumor types, including BRCA. This evidence suggests that FAM83H-AS1 is a master regulator in different cancer types, and BRCA in particular.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-71062-2