Uusi-Mäkelä Joonas, Kauppinen Maria, Seppälä Janne, Jaatinen Serafiina, Ryback Birgitta, Rantapero Tommi, Rodriguez-Martinez Alejandra, Nykter Matti, Rautajoki Kirsi J
Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
IT Management, Helsinki University Hospital, Helsinki, Finland.
Sci Rep. 2025 May 9;15(1):16220. doi: 10.1038/s41598-025-99984-9.
Long noncoding RNAs (lncRNAs) have been recently recognized as critical components of cancer biology linked to oncogenic processes. Certain lncRNAs are known to act as oncogenes, and the disease-specific expression of many lncRNAs makes them informative biomarkers. We identified 22 uncharacterized lncRNAs from RNA-seq data of 169 glioblastoma (GBM) tumor samples sequenced by The Cancer Genome Atlas (TCGA) consortium and studied their expression in TCGA diffuse glioma cohort including also IDH-mutant astrocytomas and oligodendrogliomas as well as in normal brain samples from the Genotype-Tissue Expression cohort. All of the 22 lncRNAs were clearly upregulated in diffuse gliomas samples compared to the normal brain. Interestingly, 20 (91%) of these lncRNAs had significant expression differences between tumor grades and/or entities, and 14 (64%) were associated with overall patient survival. All 22 lncRNAs were expressed in at least one of the studied GBM cell lines and 10 (45%) were expressed in all four. When six of the lncRNAs were silenced in the SNB19 GBM cell line, the knock-down was associated with reduced growth and colony formation for three lncRNAs: TCONS_l2_00001282, lnc-GBMT-6, and lnc-NBN-1. In conclusion, the studied lncRNAs are associated with survival in patients with diffuse glioma and have functional relevance in GBM.
长链非编码RNA（lncRNAs）最近被认为是与致癌过程相关的癌症生物学的关键组成部分。已知某些lncRNAs可作为癌基因，许多lncRNAs的疾病特异性表达使其成为有价值的生物标志物。我们从癌症基因组图谱（TCGA）联盟测序的169例胶质母细胞瘤（GBM）肿瘤样本的RNA测序数据中鉴定出22种未表征的lncRNAs，并研究了它们在TCGA弥漫性胶质瘤队列中的表达，该队列还包括异柠檬酸脱氢酶（IDH）突变型星形细胞瘤和少突胶质细胞瘤，以及基因型-组织表达队列中的正常脑样本。与正常脑相比，所有22种lncRNAs在弥漫性胶质瘤样本中均明显上调。有趣的是，其中20种（91%）lncRNAs在肿瘤分级和/或实体之间存在显著表达差异，14种（64%）与患者总生存期相关。所有22种lncRNAs在至少一种研究的GBM细胞系中表达，10种（45%）在所有四种细胞系中表达。当在SNB19 GBM细胞系中沉默6种lncRNAs时，三种lncRNAs（TCONS_l2_00001282、lnc-GBMT-6和lnc-NBN-1）的敲低与生长和集落形成减少相关。总之，所研究的lncRNAs与弥漫性胶质瘤患者的生存期相关，并且在GBM中具有功能相关性。
