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

Carsten Müller‐Tidow ,Danny Misiak,Fengbiao Zhou,Christian Rohde,Dennis Gerloff,Marcel Köhn,Cornelius Pauli,Ludger Hillejan,Chunhong Cui,Rainer Wiewrodt,Thomas Oellerich,Lars‐Henning Schmidt ,Bayram Edemir,Claudia Wickenhauser,Yi Liu,Stefanie Göllner,Alessandro Marra,Schraga Schwartz,Stefan Hüttelmaier,Frank Bartel

doi:10.1038/s41388-020-01570-y

Abstract

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.

Highlights

Lung cancer remains the leading cause of cancer death worldwide, with an estimated 1.6 million deaths each year [1]
That increased expression of the H/ACA box protein NOP10 was associated with a poor prognosis of Non-small cell lung cancer (NSCLC) patients and its deletion inhibited cell growth, proliferation, migration, and invasion of lung cancer cells via dysregulation of SNORA65, SNORA7A, and SNORA7B
The snoRNA-bound ribonucleoproteins (snoRNPs) complex protein NOP10 is highly expressed in NSCLC and is associated with a poor prognosis

Summary

Introduction

Lung cancer remains the leading cause of cancer death worldwide, with an estimated 1.6 million deaths each year [1]. Non-small cell lung cancer (NSCLC), the most common subtype with 85% of all cases, has an overall 5-year survival rate of 16%, which has not improved significantly for several decades [2]. Recent therapy approaches with targeted therapies and immunotherapy have somewhat. These authors contributed : Bayram Edemir, Carsten MüllerTidow

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Results

Conclusion