NOP10 predicts lung cancer prognosis and its associated small nucleolar RNAs drive proliferation and migration

• Published in: Oncogene Vol. 40; no. 5; pp. 909 - 921
• Main Authors: Cui, Chunhong, Liu, Yi, Gerloff, Dennis, Rohde, Christian, Pauli, Cornelius, Köhn, Marcel, Misiak, Danny, Oellerich, Thomas, Schwartz, Schraga, Schmidt, Lars-Henning, Wiewrodt, Rainer, Marra, Alessandro, Hillejan, Ludger, Bartel, Frank, Wickenhauser, Claudia, Hüttelmaier, Stefan, Göllner, Stefanie, Zhou, Fengbiao, Edemir, Bayram, Müller-Tidow, Carsten
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.02.2021; Nature Publishing Group
• Subjects: 13; 13/105; 13/31; 13/51; 38; 38/89; 631/67/1612/1350; 692/53/2422; Apoptosis; Biomarkers; Care and treatment; Cell Biology; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Nucleolus - genetics; Cell proliferation; Cell Proliferation - genetics; Colonies; Core protein; CRISPR; Development and progression; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical prognosis; Medicine; Medicine & Public Health; mRNA; Non-small cell lung carcinoma; Nucleoli; Nucleoproteins; Oncology; Prognosis; Pseudouridylation; Ribonucleoproteins; Ribonucleoproteins, Small Nucleolar - genetics; RNA Processing, Post-Transcriptional - genetics; RNA, Messenger - genetics; RNA, Small Nucleolar - genetics; rRNA; Small cell lung carcinoma; snoRNA; Therapeutic applications; Therapeutic targets; Tumorigenesis; Germany
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-020-01570-y

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide underlining the urgent need for new biomarkers and therapeutic targets for this disease. Long noncoding RNAs are critical players in NSCLC but the role of small RNA species is not well understood. In the present study, we investigated the role of H/ACA box small nucleolar RNAs (snoRNAs) and snoRNA-bound ribonucleoproteins (snoRNPs) in the tumorigenesis of NSCLC. H/ACA box snoRNPs including the NOP10 core protein were highly expressed in NSCLC. High levels of either NOP10 mRNA or protein were associated with poor prognosis in NSCLC patients. Loss of NOP10 and subsequent reduction of H/ACA box snoRNAs and rRNA pseudouridylation inhibited lung cancer cell growth, colony formation, migration, and invasion. A focused CRISPR/Cas9 snoRNA knockout screen revealed that genomic deletion of SNORA65, SNORA7A, and SNORA7B reduced proliferation of lung cancer cells. In line, high levels of SNORA65, SNORA7A, and SNORA7B were observed in primary lung cancer specimens with associated changes in rRNA pseudouridylation. Knockdown of either SNORA65 or SNORA7A/B inhibited growth and colony formation of NSCLC cell lines. Our data indicate that specific H/ACA box snoRNAs and snoRNA-associated proteins such as NOP10 have an oncogenic role in NSCLC providing new potential biomarkers and therapeutic targets for the disease.