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, FI-20520, Turku, Finland.
Sci Rep. 2024 Jul 23;14(1):16864. doi: 10.1038/s41598-024-67808-x.
Long non-coding RNAs (lncRNAs) have emerged as important players in cancer progression. Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastasis risk or specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNAs and protein-coding genes revealed six distinct gene clusters with one of the upregulated clusters featuring genes associated with cell motility. Upregulation of the expression of lncRNAs linked to cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed using qRT-PCR. Elevated expression of HOTTIP and LINC00543 was also noted in SCC tumors in vivo and was associated with poorer prognosis in HNSCC and lung SCC cohorts within TCGA data, respectively. Altogether, these findings uncover a novel set of lncRNAs implicated in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers and as putative therapeutic targets for locally advanced and metastatic cSCC.
长非编码 RNA（lncRNA）已成为癌症进展中的重要参与者。皮肤鳞状细胞癌（cSCC）是最常见的转移性皮肤癌，其全球发病率呈上升趋势。转移性 cSCC 的预后较差，目前尚无用于预测转移风险的既定生物标志物，也没有针对晚期或转移性 cSCC 的特定治疗靶点。为了阐明 lncRNA 在 cSCC 中的作用，对患者来源的 cSCC 细胞系和正常人类表皮角质形成细胞进行了 RNA 测序。差异表达 lncRNA 和蛋白质编码基因的相关性分析揭示了六个不同的基因簇，其中一个上调的簇具有与细胞迁移相关的基因。使用 qRT-PCR 证实了与 cSCC 细胞迁移相关的 lncRNA 在 cSCC 和头颈部 SCC（HNSCC）细胞中的表达上调。体内 SCC 肿瘤中还观察到 HOTTIP 和 LINC00543 的表达升高，并且分别与 TCGA 数据中 HNSCC 和肺 SCC 队列的预后较差相关。总之，这些发现揭示了一组新的参与 cSCC 细胞运动的 lncRNA。这些 lncRNA 可能作为潜在的新型生物标志物，并作为局部晚期和转移性 cSCC 的潜在治疗靶点。
