Correlation of Global MicroRNA Expression With Basal Cell Carcinoma Subtype

Abstract

Basal cell carcinomas (BCCs) are the most common cancers in the United States. The histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study, global miRNA expression was quantified by high-throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. Quantitative polymerase chain reaction assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies.

UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

“…For the other two important types of skin cancer, the keratinocyte-derived BCC and SCC, only sparse data documenting altered miRNA expression exist [14], [26], [27]. As a consequence, the potential role of miRNAs in the etiology of skin carcinogenesis is still poorly understood.…”

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

“…Sand et al found 16 upregulated and 10 down regulated miRNA in BCC skin with connections to HH and MAPK signaling. miR‐203 has been identified as a tumor suppressor that is suppressed by EGFR/MEK/ERK/c‐JUN signaling Heffelfinger et al found that distinctive miRNA expression correlates with nodular and infiltrative tumor BCC subtypes. Not only that but the expression level of miR‐183, a miRNA that has been shown to inhibit metastasis in various other cancers, was consistently lower in the infiltrative than nodular BCCs .…”

“…miR‐203 has been identified as a tumor suppressor that is suppressed by EGFR/MEK/ERK/c‐JUN signaling Heffelfinger et al found that distinctive miRNA expression correlates with nodular and infiltrative tumor BCC subtypes. Not only that but the expression level of miR‐183, a miRNA that has been shown to inhibit metastasis in various other cancers, was consistently lower in the infiltrative than nodular BCCs . The upregulation of MiR‐141, 200a, and 200c in nodular BCC may be linked to C‐MYC and the WNT‐β‐catenin pathway …”

“…Not only that but the expression level of miR-183, a miRNA that has been shown to inhibit metastasis in various other cancers, was consistently lower in the infiltrative than nodular BCCs. 81 The upregulation of MiR-141, 200a, and 200c in nodular BCC may be linked to C-MYC and the WNT-β-catenin pathway. 81,82 Oncogene cluster, oncomiR-1cluster (miR-17-92) has been implicated in SHH pathway regulated medulloblastoma in a PTCH1 mouse model.…”

Emerging drugs and combination strategies for basal cell carcinoma

“…Furthermore, delivery of miRNA 203 mimics to a BCC mouse model resulted in reduction of tumour growth [61]. Similarly, several different other upregulated and downregulated miRNA candidates have been identified and their pathogenesis, their specific function and therapeutic value have to be further investigated [62,63].…”