FANCD2 and BRCA1 have differential expression among the FA-BRCA genes in primary breast cancer/ Expressão diferencial de FANCD2 e BRCA1 no câncer de mama primário

The molecular pathways of DNA repair in tumors may play a role in tailoring patient therapy. The Fanconi anemia DNA repair pathway operates in the repair of DNA interstrand crosslink induced by several chemotherapeutic drugs. In this study we evaluated the expression of Fanconi anemia DNA repair genes (FANCA, C, D2, F, BRCA1 and PALB2) in 46 primary breast tumors and ten non-compromised breast samples, by Real-Time Quantitative Reverse Transcription PCR, and to correlated gene expression with breast cancer subtypes and clinico-pathological parameters. Tumor samples were classified in subtypes based on immunohistochemistry markers, and clinico-pathological parameters were obtained from the medical reports. FANCD2 was twice more expressed in tumors than in the non-compromised group (p= 0.02). BRCA1 showed a differential expression in the luminal group, three times less expressed in Luminal-B than in Luminal-A group (p= 0.01). In conclusion, the higher level of expression of FANCD2 in tumors may indicate activation of the Fanconi anemia DNA repair pathway, which has been implicated in breast carcinogenesis and in chemotherapeutic resistance. The loss of BRCA1 expression in the Luminal-B group may indicate that the use of cisplatin-based neo/adjuvant therapies is preferable, and that the use of taxol-based therapies should be avoided due to the risk of drug resistance

Characterization of MTAP gene expression in breast cancer patients and cell lines

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors\ub4 MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNB

Lnc-uc.147 Is Associated with Disease Stage of Liver, Gastric, and Renal Cancer

Lnc-uc.147, a long non-coding RNA derived from a transcribed ultraconserved region (T-UCR), was previously evidenced in breast cancer. However, the role of this region in other tumor types was not previously investigated. The present study aimed to investigate lnc-uc.147 in different types of cancer, as well as to suggest lnc-uc.147 functional and regulation aspects. From solid tumor datasets analysis of The Cancer Genome Atlas (TCGA), deregulated lnc-uc.147 expression was associated with the histologic grade of hepatocellular carcinoma, and with the tumor stage of clear cell renal and gastric adenocarcinoma. Considering the epidemiologic relevance of liver cancer, silencing lnc-uc.147 reduced the viability and clonogenic capacity of HepG2 cell lines. Additionally, we suggest a relation between the transcription factor TEAD4 and lnc-uc.147 in liver and breast cancer cells

The Potential of NORAD–PUMILIO–RALGAPB Regulatory Axis as a Biomarker in Breast Cancer

Introduction: Long non-coding RNAs (LncRNA) represent a heterogeneous family of RNAs that have emerged as regulators of various biological processes through their association with proteins in ribonucleoproteins complexes. The dynamic of these interactions can affect cell metabolism, including cancer development. Annually, breast cancer causes thousands of deaths worldwide, and searching for new biomarkers is pivotal for better diagnosis and treatment. Methods: Based on in silico prediction analysis, we focus on LncRNAs that have binding sites for PUMILIO, an RBP family involved in post-transcriptional regulation and associated with cancer progression. We compared the expression levels of these LncRNAs in breast cancer and non-tumor samples from the TCGA database. We analyzed the impact of overall and disease-free survival associated with the expression of the LncRNAs and co-expressed genes and targets of PUMILIO proteins. Results: Our results found NORAD as the most relevant LncRNA with a PUMILIO binding site in breast cancer, differently expressed between Luminal A and Basal subtypes. Additionally, NORAD was co-expressed in a Basal-like subtype (0.55) with the RALGAPB gene, a target gene of PUMILIO related to chromosome stability during cell division. Conclusion: These data suggest that this molecular axis may provide insights for developing novel therapeutic strategies for breast cancer