Ultraviolet (UV)-induced DNA mutations produce genetic drivers of cutaneous melanoma initiation and numerous neoantigens that can trigger anti-tumor immune responses in the host. Consequently, melanoma cells must rapidly evolve to evade immune detection by simultaneously modulating cell-autonomous epigenetic mechanisms and tumor-microenvironment interactions. Angiogenesis has been implicated in this process; although an increase of vasculature initiates the immune response in normal tissue, solid tumors manage to somehow enhance blood flow while preventing immune cell infiltration.
View Article and Find Full Text PDFSuper-enhancers (SEs) are stretches of enhancers ensuring a high level of expression of key genes associated with cell function. The identification of cancer-specific SE-driven genes is a powerful means for the development of innovative therapeutic strategies. Here, we identify a MITF/SOX10/TFIIH-dependent SE promoting the expression of BAHCC1 in a broad panel of melanoma cells.
View Article and Find Full Text PDFMicroRNAs are non-coding RNAs fundamental to metazoan development and disease. Although the aberrant regulation of microRNAs during mammalian tumorigenesis is well established, investigations into the contributions of individual microRNAs are wrought with conflicting observations. The underlying cause of these inconsistencies is often attributed to context-specific functions of microRNAs.
View Article and Find Full Text PDFObjective: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is a rare autosomal recessive systemic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Incidence of this genetic disorder is estimated at 1/90,000-200,000 worldwide and 1/6500-9000 in genetically isolated populations such as Iran. Here, we investigated AIRE gene mutations in eight independent Iranian non-Jewish families.
View Article and Find Full Text PDFBackground: The aim of this study was to identify germline mutation of the (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. . We examined all six hot spot exons (exons 10, 11, 13, and 14-16) of the gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases.
View Article and Find Full Text PDFBackground: , , and have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma. However, their expression level in basal cell carcinoma (BCC) has not been elucidated. We hypothesized BCC, contrary to SCC, and melanoma, could be a suitable model to study mechanisms which attenuate tumor metastasis.
View Article and Find Full Text PDFIn this study, we aimed to determine androgen receptor (AR) and SRD5A2 gene mutations in 45 patients characterised by 46,XY Disorders of Sex Differentiation (DSD) signs with normal testicular development referred to the Children's Medical Center from February 2015 to September 2017. Karyotype and sex hormone analyses were performed. Cytogenetic investigation showed that seven patients were 46,XX DSD, six patients were chromosomal DSD and 32 patients were 46,XY DSD.
View Article and Find Full Text PDFForty-five percent of the human genome is composed of Transposable Elements (TEs); therefore, TEs have had an undisputed impact on evolution of the most evolved creature by a very simple mechanism of action. Scientists have been studying this simple mechanism of action and are currently using it to develop efficient and safe gene delivery systems especially for treatment of diseases. TEs have also been used safely in generating induced Pluripotent Stem Cells (iPSC) for regenerative medicine, which opens the door to a world of possibilities in our approach in trying to wrestle with many challenges in medicine.
View Article and Find Full Text PDFBackground: BMI1, TWIST1 and SNAI2/SLUG have been implicated in aggressive behavior of squamous cell carcinoma (SCC) and melanoma and BMI1 expression could identify subtypes of Merkel cell carcinoma (MCC). However, BMI1, TWIST1 and SNAI2 expression levels in basal cell carcinomas (BCCs) have not been elucidated. We hypothesized BCC could be a good model system to decipher mechanisms which inhibit processes that drive tumor metastasis.
View Article and Find Full Text PDF