Abstract
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.
Highlights
Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide
Among the down-regulated RNAs, we identified several cancer-related transcripts, such as: fibroblast growth factor 4 (FGF4); fibroblast growth factor 21 (FGF21); leptin (LEP), Claudin 17 (CLDN17); cadherin 9 (CDH9) Tumor Necrosis Factor receptor (TNFRSF11B); BCL2-associated X (BAX); Tumor protein p53 (TP53) and Phosphatase and tensin homolog (PTEN)
Deregulation in long non coding RNAs (lncRNAs) expression has been associated with clinical outcome
Summary
Breast cancer (BRCA) is a serious public health problem, as it is the most frequent malignant tumor in women worldwide. The physical and phenotypical BRCA heterogeneity is reflected at the molecular, at gene expression (mRNAs) level This heterogeneity has been extensively studied, and evidence shows that breast cancer comprises four intrinsic groups: Luminal A, Luminal B, HER-2 enriched and Basal-like tumors[2,3]. This expression profiles are able to predict if a patient can benefit from chemotherapy or anti-hormonal therapy[5]. These useful clinical advances are focused on coding RNAs profiles only; recent evidence show that coding (messenger) RNAs represent only 34% of the total transcriptome in a human c ell[6]. Recent papers have focused on the role of long non coding RNAs (lncRNAs) in cancer biology[7,8,9,10] and in the role of specific lncRNAs in breast cancer
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