NAYARA IZABEL VIANA MOURA
Projetos de Pesquisa
Unidades Organizacionais
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Telomeric zinc-finger associated protein (TZAP) in cancer biology: friend or foe?(2021) SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; PIMENTA, Ruan; CAMARGO, Juliana Alves de; REIS, Sabrina T.; LEITE, Katia Ramos Moreira; SROUGI, MiguelThe new identified protein telomeric zinc-finger associated protein (TZAP) is a negative regulator of telomere length. Since telomere length and telomere maintenance mechanisms are essential to cancer progression, TZAP is considered a new player in cancer biology. Here we aimed to analyze TZAP using the Cancer Genome Atlas data in a Pan-Cancer approach. We gathering data from TCGA Pan-Cancer studies utilizing cBioPortal, GEPIA and UALCAN. In total we analyzed 33 types of cancer (n=9664) and their respective controls (n=711). TZAP is transcribed in all cancers but less than 5% of all tumors show any somatic changes. TZAP was downregulated in kidney chromophobe carcinoma, and upregulated in esophageal cancer, head and neck squamous cell carcinomas, kidney renal clear cell carcinoma and in liver hepatocellular carcinoma. Globally, TZAP expression is related to favorable prognosis, associated to better overall and disease-free survival. Looking to specific tumors, TZAP expression has a dual behavior. Its downregulation is associated with poor prognosis in cervical squamous cell carcinoma, in kidney renal clear cell carcinoma, kidney papillary cell carcinoma, lung adenocarcinoma and pancreas adenocarcinoma. On the contrary, in adrenocortical carcinoma, colon and rectal cancer, brain lower grade glioma and prostate adenocarcinoma the upregulation of TZAP is related with poor prognosis. TZAP expression has a positive correlation with TRF1 and TRF2 in normal tissue but not in cancer. Our analyses indicate that TZAP has an important role in oncology and may be considered as a potential biomarker.
- Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer(2023) PIMENTA, Ruan; MIOSHI, Carolina Mie; GONCALVES, Guilherme L.; CANDIDO, Patricia; CAMARGO, Juliana A.; GUIMARAES, Vanessa R.; CHIOVATTO, Caroline; GHAZARIAN, Vitoria; ROMAO, Poliana; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; VIANA, Nayara I.; REIS, Sabrina T.MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 mu g weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.
- Shorter leukocyte telomere length is associated with severity of COVID-19 infection.(2021) SANTOS, Gabriel Arantes dos; PIMENTA, Ruan; I, Nayara Viana; GUIMARAES, Vanessa R.; ROMAO, Poliana; CANDIDO, Patricia; CAMARGO, Juliana A. de; HATANAKA, Dina M.; QUEIROZ, Paula G. S.; TERUYA, Alexandre; LEITE, Katia R. M.; SROUGI, Victor; SROUGI, Miguel; REIS, Sabrina T.The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by QPCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology.
- MiR-200c-3p expression may be associated with worsening of the clinical course of patients with COVID-19(2021) PIMENTA, Ruan; I, Nayara Viana; SANTOS, Gabriel A. dos; CANDIDO, Patricia; GUIMARAES, Vanessa R.; ROMAO, Poliana; SILVA, Iran A.; CAMARGO, Juliana A. de; HATANAKA, Dina M.; QUEIROZ, Paula G. S.; TERUYA, Alexandre; ECHENIQUE, Leandro; BESEN, Bruno A. M. P.; LEITE, Katia R. M.; SROUGI, Victor; SROUGI, Miguel; REIS, Sabrina T.COVID-19 represents a public health emergency, whose mechanism of which is not fully understood. It is speculated that microRNAs may play a crucial role in host cells after infection by SARS-CoV-2. Thus, our study aimed to analyze the expression of miR-200c-3p in saliva samples from patients with COVID-19. One handred eleven samples from patients with COVID-19 were divided into 4 groups. Group I: 39 patients negative for Covid-19; Group II: 37 positive and symptomatic patients, with no indication of hospitalization; Group III: 21 patients with respiratory disorders (hospitalized); Group W: 14 patients with severe conditions (oxygen therapy). The expression levels of miR-200c-3p were determined using qPCR. We found greater expression of miR-200c-3p in patients in group W (p<0.0001), and also verified that patients aged >= 42 years had a higher expression of this miR (p=0.013). Logistic regression analysis revealed that the expression of miR-200c-3p and systemic arterial hypertension are factors independently associated with patients in group IV (p<0.0001). Our results suggest that miR-200c-3p is a predictor of severity independent of COVID-19 risk factors, which could represent a way of screening patients affected by SARS-CoV-2.
- Treating metastatic prostate cancer with microRNA-145(2018) ISCAIFE, Alexandre; REIS, Sabrina Thalita; MORAIS, Denis Reis; VIANA, Nayara Izabel; SILVA, Iran Amorim da; PIMENTA, Ruan; BORDINI, Andre; DIP, Nelson; SROUGI, Miguel; LEITE, Katia Ramos MoreiraProstate cancer (PCa) is an incurable disease at the metastatic stage. Although there are different options for treatment, the results are limited. MicroRNAs (miRNAs) are a group of small, noncoding, regulatory RNAs with important roles in regulating gene expression. miR-145 is reported to be a key tumor suppressor miRNA (tsmiR) that controls important oncogenes, such as MYC and RAS. In this study, in vitro studies were performed to show the control of MYC and RAS by miR-145. Flow cytometry was used to analyze cell proliferation and apoptosis. The efficacy of miR-145 in treating metastatic PCa was tested in nude mice using a model of bone metastasis promoted by intraventricular injection of PC-3MLuc-C6 cells. Tumor growth was evaluated by an in vivo bioluminescence system. After the full establishment of metastases on day 21, six animals were treated with three intravenous doses of miR-145 (on days 21, 24 and 27), and six were injected with scramble miRNA as controls. Compared to the controls, tumor growth was significantly reduced in animals receiving miR-145, most importantly on day 7 after the third and last dose of miRNA. After discontinuing the treatment, tumor growth resumed, becoming similar to the group of non-treated animals. A decrease in MYC and RAS expression was observed in all cell lines after treatment with miR-145, although statistical significance was achieved only in experiments with LNCaP and PC3 cell lines, with a decrease in 56% (p = 0.012) and 31% (p = 0.013) of RAS expression, respectively. Our results suggest that miR-145 is a potential molecule to be tested for treatment of metastatic, castration-resistant PCa.
- Tissue expression of MMP-9, TIMP-1, RECK, and miR338-3p in prostate gland: can it predict cancer?(2021) MORAES, Rodolfo Pacheco de; PIMENTA, Ruan; MORI, Fernando Noboru Cabral; SANTOS, Gabriel Arantes dos; VIANA, Nayara Izabel; GUIMARAES, Vanessa Ribeiro; CAMARGO, Juliana Alves de; MOREIRA-LEITE', Katia Ramos; SROUGI, Miguel; NAHAS, William Carlos; REIS, Sabrina T.Prostate cancer is the most frequent malignancy affecting men worldwide. Due to the low sensitivity and specificity of the prostate-specific antigen test and the digital rectal exam as screening modalities, several alternatives are being studied. This study aimed to evaluate the application of MMP-9 and its regulators (TIMP-1, RECK, and miR-338-3p) as diagnostic and prognostic indicators of prostate cancer. A total of 134 randomly selected patients under investigation for prostate cancer submitted to a transrectal ultrasound-guided prostate biopsy were enrolled in the study; of these, 61 were positive for the disease (cases), and 73 were negative (control group). The tissue samples were further analyzed by gene and miR-338-3p expression analysis using qRT-PCR (one randomly selected fragment of each patient). Approximately 58% of the patients with prostate cancer presented MMP9 upregulation, while 73%, 65%, and 69% downregulated IMP-1, RECK, and miR-338-3p, respectively. MiR-338-3p was expressed at lower levels in patients with PSA concentrations exceeding 20 ng/mL (p=0.045) and abnormal DRE (p=0.006), while the RECK was more expressed in patients with abnormal DRE (p=0.01). We found that most patients with prostate cancer overexpressed MMP-9; on the other hand, most of them underexpressed TIMP-1, RECK, and miR-338-3p. MiR-338-3p presented as a possible predictor of poor prognosis. Further studies are warranted to evaluate these biomarkers as prognosis factors better.
- Can increased expression of miR-Let-7c reduce the transition potential of high-grade urothelial carcinoma?(2021) GOMES, Paulo Ricardo da Silva; CANDIDO, Patricia; GHAZARIAN, Vitoria; CAMARGO, Juliana A.; GUIMARAES, Vanessa R.; GONCALVES, Guilherme L.; ROMAO, Poliana; SILVA, Iran A.; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; REIS, Sabrina T.; PIMENTA, Ruan; VIANA, Nayara IzabelBackground Bladder cancer is the leading transitional cell carcinoma affecting men and women with high morbidity and mortality rates, justifying the need to develop new molecular target therapies using microRNAs. This study aimed to evaluate the behavior of the T24 cell line after transfection with miR-Let-7c precursor mimic through invasion, migration, apoptosis, and cell cycle assays. Methods and results T24 cell was transfected with the Let-7c mimic and its respective control and evaluated after 24 h. The expression levels of miR-Let-7c were analyzed by qPCR. We performed wound healing, Matrigel and flow cytometry, apoptosis, and cell cycle assays to determine its effect on cellular processes. Cells transfected with miR-Let-7c showed increased apoptosis rates (p = 0.019), decreased migration 24 h (p = 0.031) and 48 h (p = 0.0006), invasion potential (p = 0.0007), and cell proliferation (p = 0.002). Conclusions Our results demonstrate that miR-Let-7c can act in different pathways of the carcinogenic cellular processes of muscle-invasive urothelial carcinoma cells, inhibiting cell proliferation and increasing apoptosis levels, consequently limiting their invasion potential. However, further studies should be carried out better to elucidate this microRNA's role in high-grade urothelial carcinomas and unveil which targets this microRNA may present, which are intrinsically related to the cancer survival pathways.
- Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model(2023) PIMENTA, Ruan; CAMARGO, Juliana A.; GONCALVES, Guilherme L.; GHAZARIAN, Vitoria; CANDIDO, Patricia; GUIMARAES, Vanessa R.; ROMAO, Poliana; CHIOVATTO, Caroline; SILVA, Karina Serafim da; SANTOS, Gabriel A. dos; SILVA, Iran A.; NAHAS, William C.; LEITE, Katia R.; PESSOA, Ana Flavia Marcal; VIANA, Nayara I.; REIS, Sabrina T.BackgroundPreviously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia.Methods and resultsIn vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 & mu;g/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation.ConclusionOur results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.
- The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer(2023) CAMARGO, Juliana A.; VIANA, Nayara I.; PIMENTA, Ruan; GUIMARAES, Vanessa R.; SANTOS, Gabriel A. dos; CANDIDO, Patricia; GHAZARIAN, Vitoria; ROMAO, Poliana; SILVA, Iran A.; BIRBRAIR, Alexander; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; TRARBACH, Ericka B.; REIS, Sabrina T.Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.