Abstract
Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin (n = 15; control group) and tissues at tumor centers from patients with cheek BCC (n = 15; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the “basal cell carcinoma pathways” were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.
Highlights
Basal cell carcinoma (BCC) is the most ordinary human solid tumor in the skin, accounting for approximately 80% of nonmelanoma skin cancers [1, 2]
We identified a group of differentially expressed miRNAs (DEMs), which is far more than the number of DEMs that were previously reported in BCCs (e.g., 26 DEMs [1] and 33 upregulated miRNAs [2])
We identified Gene Ontology (GO) terms that are primarily involved in the immune response and metabolism, which are expected as disturbances in the immune system and metabolism and have been widely demonstrated across tumors such as BCCs [33, 34]
Summary
Basal cell carcinoma (BCC) is the most ordinary human solid tumor in the skin, accounting for approximately 80% of nonmelanoma skin cancers [1, 2]. Most BCC patients usually exhibit translucent lesions in superficial and develop symptoms such as bleeding and crusting. From the first case described by Krompecher in 1900, several investigations have been conducted to uncover the molecular pathogenesis of BCC. Several tumor-promoting signal transduction pathways have been reported, such as the sonic hedgehog (Shh) and mitogen-activated protein kinase/extracellular signalregulated kinase (Mapk/Erk) pathways [1, 2, 5]. Several genes/proteins have been reported to be associated with the development of BCC. The patched (Ptch1) receptor binding to the Shh ligand casts impacts on the smoothened protein (Smo) on the cell membrane, which
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