Piipponen Minna, Riihilä Pilvi, Knuutila Jaakko S, Kallajoki Markku, Kähäri Veli-Matti, Nissinen Liisa
Department of Dermatology, University of Turku and Turku University Hospital, Hämeentie 11 TE6, FI-20520 Turku, Finland.
FICAN West Cancer Centre Research Laboratory, University of Turku and Turku University Hospital, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
Cancers (Basel). 2022 Aug 17;14(16):3980. doi: 10.3390/cancers14163980.
Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer progression. Super enhancers (SE) play a role in tumorigenesis and regulate the expression of specific lncRNAs. We examined the role of , also named , in cutaneous squamous cell carcinoma (cSCC). Elevated () expression was detected in cSCC cells, and expression was downregulated by SE inhibitors THZ1 and JQ1 and via the MEK1/ERK1/2 pathway. Increased expression of () was noted in tumor cells in cSCCs and their metastases compared to normal skin, actinic keratoses, and cSCCs in situ. Higher () expression was noted in metastatic cSCCs than in non-metastatic cSCCs. RNA-seq analysis after () knockdown revealed significantly regulated GO terms , , , and KEGG pathway Among the top-regulated genes were , , and . Knockdown of () resulted in decreased production of MMP-1 and MMP-13 by cSCC cells, suppressed invasion of cSCC cells through collagen I, and growth of human cSCC xenografts in vivo. Based on these observations, () was named (super enhancer and ERK1/2-Regulated Long Intergenic non-protein coding transcript Overexpressed in Carcinomas). These results reveal the role of in cSCC invasion and identify it as a potential therapeutic target in advanced cSCC.
长链非编码RNA（lncRNAs）已成为癌症进展的重要调节因子。超级增强子（SE）在肿瘤发生中起作用，并调节特定lncRNAs的表达。我们研究了也被称为 的 在皮肤鳞状细胞癌（cSCC）中的作用。在cSCC细胞中检测到 （ ）表达升高，并且其表达被SE抑制剂THZ1和JQ1以及通过MEK1/ERK1/2途径下调。与正常皮肤、光化性角化病和原位cSCC相比，在cSCC及其转移灶的肿瘤细胞中观察到 （ ）表达增加。转移性cSCC中的 （ ）表达高于非转移性cSCC。 （ ）敲低后的RNA测序分析显示显著调控的基因本体术语 、 、 以及KEGG通路 。在调控最显著的基因中有 、 和 。 （ ）敲低导致cSCC细胞产生MMP-1和MMP-13减少，抑制cSCC细胞通过I型胶原的侵袭以及人cSCC异种移植瘤在体内的生长。基于这些观察结果， （ ）被命名为 （超级增强子和ERK1/2调节的在癌中过表达的长基因间非蛋白质编码转录本）。这些结果揭示了 在cSCC侵袭中的作用，并将其确定为晚期cSCC的潜在治疗靶点。
