Expression of microRNAs in Basal Cell Carcinoma
Expression of microRNAs in Basal Cell Carcinoma
Background Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin.
Objectives To initiate a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC.
Methods Patients with BCC (n= 7) were included in this study. Punch biopsies were harvested from the tumour centre (lesional, n= 7) and from adjacent nonlesional skin (intraindividual control, n= 7). Microarray-based miRNA expression profiles were obtained on an Agilent platform using miRBase 16 screening for 1205 Homo sapiens (hsa)-miRNA candidates. To validate the microarray data, the expression of seven dysregulated miRNAs was measured by TaqMan quantitative real-time reverse transcription polymerase chain reaction.
Results We identified 16 significantly upregulated (hsa-miR-17, hsa-miR-18a, hsa-miR-18b, hsa-miR-19b, hsa-miR-19b-1*, hsa-miR-93, hsa-miR-106b, hsa-miR-125a-5p, hsa-miR-130a, hsa-miR-181c, hsa-miR-181c*, hsa-miR-181d, hsa-miR-182, hsa-miR-455-3p, hsa-miR-455-5p and hsa-miR-542-5p) and 10 significantly downregulated (hsa-miR-29c, hsa-miR-29c*, hsa-miR-139-5p, hsa-miR-140-3p, hsa-miR-145, hsa-miR-378, hsa-miR-572, hsa-miR-638, hsa-miR-2861 and hsa-miR-3196) miRNAs in BCC compared with nonlesional skin. Data mining revealed connections to many tumour-promoting pathways, such as the Hedgehog and the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling cascades.
Conclusions This study identified several miRNA candidates that may play a role in the molecular pathogenesis of BCC.
Basal cell carcinoma (BCC) of the skin is the most common cancer in humans. Although first described by Krompecher in 1900, the molecular pathogenesis of BCC has yet to be completely understood. Various different tumour-promoting signalling cascades, including the Hedgehog (HH) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, have been reported to play a role in BCC development.
MicroRNAs (miRNAs) are a relatively new class of short RNAs that are involved in post-transcriptional gene regulation, but they have not been extensively studied with respect to the molecular pathogenesis of BCC. Because it is estimated that 30–60% of all human genes are controlled by miRNAs, a potential role for miRNAs in the molecular pathogenesis of BCC deserves investigation. As a class, miRNAs have been implicated in a variety of physiological and pathophysiological processes of the skin and other tissues of the human body. Recently, the miRNA maturing enzymes Drosha and Dicer, as well as pivotal parts of the miRNA microprocessor complex and the miRNA effector RNA-induced silencing complex, were reported to be dysregulated in epithelial skin tumours, including BCC. Based on these preliminary reports of alterations in the miRNA machinery, we initiated a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC.
Abstract and Introduction
Abstract
Background Perturbations in the expression profiles of microRNAs (miRNAs) have been reported for a variety of different cancers. Differentially expressed miRNAs have not been systematically evaluated in basal cell carcinoma (BCC) of the skin.
Objectives To initiate a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC.
Methods Patients with BCC (n= 7) were included in this study. Punch biopsies were harvested from the tumour centre (lesional, n= 7) and from adjacent nonlesional skin (intraindividual control, n= 7). Microarray-based miRNA expression profiles were obtained on an Agilent platform using miRBase 16 screening for 1205 Homo sapiens (hsa)-miRNA candidates. To validate the microarray data, the expression of seven dysregulated miRNAs was measured by TaqMan quantitative real-time reverse transcription polymerase chain reaction.
Results We identified 16 significantly upregulated (hsa-miR-17, hsa-miR-18a, hsa-miR-18b, hsa-miR-19b, hsa-miR-19b-1*, hsa-miR-93, hsa-miR-106b, hsa-miR-125a-5p, hsa-miR-130a, hsa-miR-181c, hsa-miR-181c*, hsa-miR-181d, hsa-miR-182, hsa-miR-455-3p, hsa-miR-455-5p and hsa-miR-542-5p) and 10 significantly downregulated (hsa-miR-29c, hsa-miR-29c*, hsa-miR-139-5p, hsa-miR-140-3p, hsa-miR-145, hsa-miR-378, hsa-miR-572, hsa-miR-638, hsa-miR-2861 and hsa-miR-3196) miRNAs in BCC compared with nonlesional skin. Data mining revealed connections to many tumour-promoting pathways, such as the Hedgehog and the mitogen-activated protein kinase/extracellular signal-regulated kinase signalling cascades.
Conclusions This study identified several miRNA candidates that may play a role in the molecular pathogenesis of BCC.
Introduction
Basal cell carcinoma (BCC) of the skin is the most common cancer in humans. Although first described by Krompecher in 1900, the molecular pathogenesis of BCC has yet to be completely understood. Various different tumour-promoting signalling cascades, including the Hedgehog (HH) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, have been reported to play a role in BCC development.
MicroRNAs (miRNAs) are a relatively new class of short RNAs that are involved in post-transcriptional gene regulation, but they have not been extensively studied with respect to the molecular pathogenesis of BCC. Because it is estimated that 30–60% of all human genes are controlled by miRNAs, a potential role for miRNAs in the molecular pathogenesis of BCC deserves investigation. As a class, miRNAs have been implicated in a variety of physiological and pathophysiological processes of the skin and other tissues of the human body. Recently, the miRNA maturing enzymes Drosha and Dicer, as well as pivotal parts of the miRNA microprocessor complex and the miRNA effector RNA-induced silencing complex, were reported to be dysregulated in epithelial skin tumours, including BCC. Based on these preliminary reports of alterations in the miRNA machinery, we initiated a microarray-based miRNA profiling study to identify specific miRNA candidates that are differentially expressed in BCC.
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