Davanian Haleh, Balasiddaiah Anangi, Heymann Robert, Sundström Magnus, Redenström Poppy, Silfverberg Mikael, Brodin David, Sällberg Matti, Lindskog Sven, Kruger Weiner Carina, Chen Margaret
Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.
Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
Oncotarget. 2017 Jan 17;8(3):4530-4542. doi: 10.18632/oncotarget.13889.
Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumourgenesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncRNAs accompanied by signalling pathways of cancer, spliceosome, mRNA surveillance and Wnt. Further validation in an independent cohort points out the long non-coding (lncRNAs) and small nucleolar RNA (snoRNAs): LINC340, SNORD116-25, SNORA11, SNORA21, SNORA47 and SNORA65 as a distinct ncRNA signature of ameloblastoma. Importantly, the presence of these ncRNAs was independent of BRAF-V600E and SMO-L412F mutations, histology type or tumour location, but was positively correlated with the tumour size. Taken together, this study shows a systematic investigation of ncRNA expression of ameloblastoma, and illuminates new diagnostic and therapeutic targets for this invasive odontogenic tumour.
颌骨成釉细胞瘤仍然是最难治疗的牙源性肿瘤，且复发率很高。新证据表明，非编码RNA（ncRNA）在肿瘤发生和癌症预后中起关键作用。然而，成釉细胞瘤的ncRNA表达数据尚缺。在此，我们首次报告了成釉细胞瘤的ncRNA特征。在这项两步分析中，共使用了95例成釉细胞瘤病例以及一种覆盖超过285,000条全长转录本的全球阵列转录组技术。该分析首先在一个测试队列中鉴定出31种上调的成釉细胞瘤相关ncRNA，它们伴随着癌症、剪接体、mRNA监测和Wnt信号通路。在一个独立队列中的进一步验证指出，长链非编码RNA（lncRNA）和小核仁RNA（snoRNA）：LINC340、SNORD116 - 25、SNORA11、SNORA21、SNORA47和SNORA65是成釉细胞瘤独特的ncRNA特征。重要的是，这些ncRNA的存在与BRAF - V600E和SMO - L412F突变、组织学类型或肿瘤位置无关，但与肿瘤大小呈正相关。综上所述，本研究对成釉细胞瘤的ncRNA表达进行了系统研究，并为这种侵袭性牙源性肿瘤阐明了新的诊断和治疗靶点。
