全面分析皮肤鳞状细胞癌的编码和非编码转录组变化。

A comprehensive analysis of coding and non-coding transcriptomic changes in cutaneous squamous cell carcinoma.

机构信息

Dermatology and Venereology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Sci Rep. 2020 Feb 27;10(1):3637. doi: 10.1038/s41598-020-59660-6.

Cutaneous Squamous Cell Carcinoma (cSCC) is the most common and fastest-increasing cancer with metastatic potential. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are novel regulators of gene expression. To identify mRNAs, lncRNAs and circRNAs, which can be involved in cSCC, RNA-seq was performed on nine cSCCs and seven healthy skin samples. Representative transcripts were validated by NanoString nCounter assays using an extended cohort, which also included samples from pre-cancerous skin lesions (actinic keratosis). 5,352 protein-coding genes, 908 lncRNAs and 55 circular RNAs were identified to be differentially expressed in cSCC. Targets of 519 transcription factors were enriched among differentially expressed genes, 105 of which displayed altered level in cSCCs, including fundamental regulators of skin development (MYC, RELA, ETS1, TP63). Pathways related to cell cycle, apoptosis, inflammation and epidermal differentiation were enriched. In addition to known oncogenic lncRNAs (PVT1, LUCAT1, CASC9), a set of skin-specific lncRNAs were were identified to be dysregulated. A global downregulation of circRNAs was observed in cSCC, and novel skin-enriched circRNAs, circ_IFFO2 and circ_POF1B, were identified and validated. In conclusion, a reference set of coding and non-coding transcripts were identified in cSCC, which may become potential therapeutic targets or biomarkers.

皮肤鳞状细胞癌（cSCC）是最常见且增长最快的具有转移潜能的癌症。长链非编码 RNA（lncRNA）和环状 RNA（circRNA）是基因表达的新型调控因子。为了鉴定可能参与 cSCC 的 mRNAs、lncRNA 和 circRNA，对 9 例 cSCC 和 7 例健康皮肤样本进行了 RNA-seq 分析。使用扩展队列的 NanoString nCounter 检测对代表性转录本进行了验证，该队列还包括来自癌前皮肤病变（光化性角化病）的样本。在 cSCC 中鉴定出 5,352 个蛋白编码基因、908 个 lncRNA 和 55 个环状 RNA 存在差异表达。差异表达基因中富集了 519 个转录因子的靶标，其中 105 个在 cSCC 中显示出改变的水平，包括皮肤发育的基本调控因子（MYC、RELA、ETS1、TP63）。与细胞周期、凋亡、炎症和表皮分化相关的途径被富集。除了已知的致癌性 lncRNA（PVT1、LUCAT1、CASC9）外，还鉴定出一组失调的皮肤特异性 lncRNA。在 cSCC 中观察到 circRNA 的整体下调，并且鉴定和验证了新型皮肤富集的 circRNA，circ_IFFO2 和 circ_POF1B。总之，在 cSCC 中鉴定出了编码和非编码转录本的参考集，它们可能成为潜在的治疗靶点或生物标志物。