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Small nucleolar RNA signatures of lung tumor-initiating cells
BACKGROUND: Non-small cell lung cancer (NSCLC) is the number one cancer killer. Tumor-initiating cells (TICs) are responsible for tumor progression and recurrence. Emerging evidences suggest that small nucleolar RNAs (snoRNAs) play malfunctioning roles in lung tumorigenesis. This study aims to deter...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029979/ https://www.ncbi.nlm.nih.gov/pubmed/24886050 http://dx.doi.org/10.1186/1476-4598-13-104 |
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author | Mannoor, Kaiissar Shen, Jun Liao, Jipei Liu, Zhenqiu Jiang, Feng |
author_facet | Mannoor, Kaiissar Shen, Jun Liao, Jipei Liu, Zhenqiu Jiang, Feng |
author_sort | Mannoor, Kaiissar |
collection | PubMed |
description | BACKGROUND: Non-small cell lung cancer (NSCLC) is the number one cancer killer. Tumor-initiating cells (TICs) are responsible for tumor progression and recurrence. Emerging evidences suggest that small nucleolar RNAs (snoRNAs) play malfunctioning roles in lung tumorigenesis. This study aims to determine if snoRNAs have important function in lung TICs by: 1) profiling and comparing snoRNA expression patterns in lung ALDH1+/- cells of 28 primary NSCLC tissues to identify new signatures of TICs; 2) determining prognostic significance of the snoRNA signatures by analyzing the expression in 82 NSCLC tissues with different stages and histological types using quantitative PCR; 3) functionally investigating if the snoRNAs contribute to stemness of lung TICs using in vitro and in vivo assays. RESULTS: Twenty-two snoRNAs were identified whose changes were specific to the TICs. The expression of two snoRNAs (snoRA3 and snoRA42) was inversely associated with survival of NSCLC patients (P = 0.002, p = 0.001, respectively). Functional analysis indicated that snoRA42 was upregulated in CD133+ cells isolated from NSCLC cell lines compared with the CD133- counterparts. snoRA42 knockdown reduced the proliferation and self-renewal of TICs in vitro. However, ectopic expression of snoRA42 in non-TICs enhanced the potentials of cell proliferation and self-renewal. snoRA42 expression was associated with expression of stem cell-core transcription factors in lung TICs. Blocking snoRA42 expression in TIC xenografts decreased tumorigenesis in mice. CONCLUSIONS: The snoRNA signatures of lung TICs provide potential biomarkers for predicting outcome of NSCLC. snoRA42 is one of the important snoRNAs in regulating features of lung TICs, and thus contributes to lung tumorigenesis. |
format | Online Article Text |
id | pubmed-4029979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40299792014-05-22 Small nucleolar RNA signatures of lung tumor-initiating cells Mannoor, Kaiissar Shen, Jun Liao, Jipei Liu, Zhenqiu Jiang, Feng Mol Cancer Research BACKGROUND: Non-small cell lung cancer (NSCLC) is the number one cancer killer. Tumor-initiating cells (TICs) are responsible for tumor progression and recurrence. Emerging evidences suggest that small nucleolar RNAs (snoRNAs) play malfunctioning roles in lung tumorigenesis. This study aims to determine if snoRNAs have important function in lung TICs by: 1) profiling and comparing snoRNA expression patterns in lung ALDH1+/- cells of 28 primary NSCLC tissues to identify new signatures of TICs; 2) determining prognostic significance of the snoRNA signatures by analyzing the expression in 82 NSCLC tissues with different stages and histological types using quantitative PCR; 3) functionally investigating if the snoRNAs contribute to stemness of lung TICs using in vitro and in vivo assays. RESULTS: Twenty-two snoRNAs were identified whose changes were specific to the TICs. The expression of two snoRNAs (snoRA3 and snoRA42) was inversely associated with survival of NSCLC patients (P = 0.002, p = 0.001, respectively). Functional analysis indicated that snoRA42 was upregulated in CD133+ cells isolated from NSCLC cell lines compared with the CD133- counterparts. snoRA42 knockdown reduced the proliferation and self-renewal of TICs in vitro. However, ectopic expression of snoRA42 in non-TICs enhanced the potentials of cell proliferation and self-renewal. snoRA42 expression was associated with expression of stem cell-core transcription factors in lung TICs. Blocking snoRA42 expression in TIC xenografts decreased tumorigenesis in mice. CONCLUSIONS: The snoRNA signatures of lung TICs provide potential biomarkers for predicting outcome of NSCLC. snoRA42 is one of the important snoRNAs in regulating features of lung TICs, and thus contributes to lung tumorigenesis. BioMed Central 2014-05-06 /pmc/articles/PMC4029979/ /pubmed/24886050 http://dx.doi.org/10.1186/1476-4598-13-104 Text en Copyright © 2014 Mannoor et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Mannoor, Kaiissar Shen, Jun Liao, Jipei Liu, Zhenqiu Jiang, Feng Small nucleolar RNA signatures of lung tumor-initiating cells |
title | Small nucleolar RNA signatures of lung tumor-initiating cells |
title_full | Small nucleolar RNA signatures of lung tumor-initiating cells |
title_fullStr | Small nucleolar RNA signatures of lung tumor-initiating cells |
title_full_unstemmed | Small nucleolar RNA signatures of lung tumor-initiating cells |
title_short | Small nucleolar RNA signatures of lung tumor-initiating cells |
title_sort | small nucleolar rna signatures of lung tumor-initiating cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029979/ https://www.ncbi.nlm.nih.gov/pubmed/24886050 http://dx.doi.org/10.1186/1476-4598-13-104 |
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