Tag Archives

One Article

Posted by rsg2sec on

A NEW APPROACH TO RESEARCH THERAPEUTIC TARGETS FOR TRIPLE NEGATIVE BREAST CANCER: INVESTIGATION OF THE ASSOCIATION BETWEEN TUMOR GENOME AMPLIFIED REGIONS AND COMPETING ENDOGENOUS RNAS NETWORKS

A NEW APPROACH TO RESEARCH THERAPEUTIC TARGETS FOR TRIPLE NEGATIVE BREAST CANCER: INVESTIGATION OF THE ASSOCIATION BETWEEN TUMOR GENOME AMPLIFIED REGIONS AND COMPETING ENDOGENOUS RNAS NETWORKS

Igor S. Giner, Leandro E. Garcia, Bruna M. Sugita, Luciane R. Cavalli, Enilze Ribeiro, Jaqueline C. Oliveira and Daniela F. Gradia

Breast cancer (BC) is the second most common type of cancer in women in Brazil. By immunohistochemistry, BC is divided into four subtypes, among which the Triple Negative (TN) is the most aggressive. This subtype has no specific diagnosis or therapy. Thus, the research of therapeutic targets and biomarkers for TN BC is encouraged. It is known that competing endogenous RNAs (ceRNAs) networks are RNA-miRNA-RNA interaction networks that result in gene expression modification. Copy number alterations (CNAs) are gain or loss changes of chromosomal segments. We hypothesize that genome amplified regions in TN tumors may stimulate the formation of ceRNAs networks; this association’s investigation may be an alternative strategy for researching TN BC biomarkers and therapeutic targets. We aimed to identify potential ceRNAs transcribed in TN tumors genome amplified regions and explore this mechanism’s potential in the TN BC carcinogenesis regulation. A previous study realized by the research group identified CNAs in TN (n = 29) and Non-Triple Negative (n = 16) breast tumors using array-CGH. With this data, we performed a computational prediction of ceRNAs networks between transcripts from genome amplified regions in TN tumors and transcripts from the total transcriptome of Basal tumors (a molecular BC subtype, considered correspondent to TN in this study) – using the GDCRNATools package in the R software. We found a possible network of 8 pairs of overexpressed ceRNAs (logFC> 0.58, p-value ≤ 0.01, and positive correlation). Present in this network, TMPO-AS1 is a lncRNA with oncogenic functions already validated. The mir-302 and mir-520 miRNA families, described as tumor suppressors in the literature, are the most frequent in our network. The ceRNAs network around TMPO-AS1 and the most frequent miRNA families present themselves as potential candidates for specific TN BC therapy – showing that our analysis strategy can be an alternative to traditional research methodologies.