EAR ATRESIA: IS THERE A ROLE FOR APOPTOSIS REGULATING miRNAs?

Abstract

OBJECTIVE:The molecular events underlying ear development involve numerous regulatory molecules; however, the role of microRNAs (miRNAs) has not been explored in patients with ear atresia. Here, we aimed to investigate the expressions of 20–22 nucleotide noncoding RNAs.METHODS:We selected 12 miRNAs that function to control post-transcriptional gene expression in different pathways, including apoptosis, angiogenesis, and chondrogenesis. The altered miRNA expressions were analyzed by real-time PCR from serum samples of 7 patients with ear atresia and 8 controls.RESULTS:We found that the expression of apoptosis-regulating miRNAs was significantly downregulated in patients with ear atresia. TThe expressions of miR126, miR146a, miR222, and miR21 were significantly decreased by 76.2-(p=0.041), 61.8-(p=0.000), 30.5-(p=0.009), and 71.21-fold (p=0.042), respectively, compared with controls.CONCLUSION:Abnormal ear development in ear atresia patients, could possibly be due to the reduced expression of apoptosis regulating miRNAs. Changes in the regulation of tumor protein p53 (TP53), p53 upregulated modulator of apoptosis (PUMA), Fas cell surface death receptor (FAS), FAS ligand (FasL), and phosphatase and tensin homolog (PTEN) directly or within the apoptosis-related cascades may play important roles during development, particularly in the external ear. This is the first report to present the possible association between apoptosis-regulating miRNAs and ear atresia/microtia.

Comparison of miRNA expressions among benign, premalignant and malignant lesions of the larynx: Could they be transformation biomarkers?

“…MicroRNAs (miRNA) are endogenous, small, non-coding RNAs that are 21–24 nucleotides in length and known to regulate gene expression by silencing target transcripts via complement base-pairing in various pathways including embryogenesis, development, differentiation, and apoptosis [ 3 ]. miRNAs are also reported to regulate other pathological and physiological processes including cancer [ 4 – 6 ]. Since the protooncogenic and tumor-suppressive effects of miRNAs have been shown, miRNAs have also been investigated in head and neck cancers beside others [ 6 ].…”

Research Article Expression of microRNAs miR-126 and miR-873 and genes CASPASE-8 and C-FLIP in neurospheres of Glioblastoma lines U-343 subjected to treatment with ionizing radiation and temozolomide.

“…The targets of the microRNAs correspond to 30% of all genes encoding proteins. As the miRNAs have several functions, among them, control of cell differentiation, proliferation and apoptosis; aberrant expression and dysregulation contribute to tumorigenesis, angiogenesis and metastasis, and may serve as tumor suppressor or oncogenes (Li et al, 2013) In relation to apoptosis, there are two routes: intrinsic pathway also known as mitochondrial, triggered by intracellular stimuli (DNA damage, treatment with cytotoxic drugs, lack of growth factors and / or oxidative stress); this pathway is dependent on the formation of apoptosome (compound of pro-caspase-9) activation factor of apoptotic protease 1 (Apaf-1) (Verbrugge et al, 2010;Zhenyi et al, 2015;Aslan et al, 2018).…”

“…On the other hand, the extrinsic pathway of apoptosis is initiated by the ligands of death (ligand Faz, TRAIL, TNF-α), then this interaction, followed by the assembly of the death inducer signaling complex (DISC) containing Fas protein FADD) and procaspase-8 and procaspase-10. Thus, caspases-3/6/7 induce the end of the cell or end up cleaving Bcl-2, Bid to form the tBid which thus trigger the intrinsic apoptosis pathway that is mediated by mitochondria (Verbrugge et al, 2010;Zhenyi et al, 2015;Aslan et al, 2018).…”

Expressão dos microRNAs miR-126 e miR-873 e dos genes CASPASE-8 e C-FLIP em neuroesferas em linhagens de Glioblastoma U 343 submetidas ao tratamento com Radiação Ionizante e Temozolomida

“…Sendo o glioblastoma o mais frequente, com incidência de 3-4/100.000 (MCNEILL, et al 2015). A maioria dos diagnósticos são feitos em pacientes idosos, na quinta ou sexta década de vida quando GBM primário; em GBM secundário ocorre em pacientes mais jovens, antes dos 45 anos de idade (ALDAPE, et al 2015;SEYSTAHL, et al 2016 tratamento com drogas citotóxicas, falta de fatores de crescimento e/ou estresse oxidativo); essa via é dependente da formação do apoptossoma composto de: PRO-CASPASE-9, fator de ativação da protease apoptótica 1 (APAF-1) e CITOCROMO-C (ASLAN, et al 2018;VERBRUGGE, et al 2010;ZHENYI, et al 2015).…”

“…Já a via extrínseca da apoptose, inicia-se pelos ligantes de morte (ligante FAS, TRAIL, TNF-α), onde esta interação, seguida pela montagem do complexo de sinalização do indutor de morte (DISC) que contém a proteína FAS (FADD) e a PROCASPASE-8 e PROCASPASE-10. Logo, as CASPASES-3/6/7 induzem a morte da célula ou acabam clivando a BCL-2 e BID formando a t-Bid que assim desencadeiam a via de intrínseca ou via mitocondrial (ASLAN, et al 2018;VERBRUGGE, et al 2010;ZHENYI, et al 2015).…”