Small nucleolar RNA signatures of lung tumor-initiating cells.
Small nucleolar RNA signatures of lung tumor-initiating cells.
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DOI：
10.1186/1476-4598-13-104
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发表时间：
2014-05-06
期刊：
影响因子：
37.3
通讯作者：
Jiang F
中科院分区：
文献类型：
--
作者：
Mannoor K;Shen J;Liao J;Liu Z;Jiang F
非小细胞肺癌（Non-small cell lung cancer，NSCLC）是一种常见的恶性肿瘤。肿瘤起始细胞（TIC）负责肿瘤进展和复发。新的证据表明，小核仁RNA（snoRNA）在肺肿瘤发生中发挥功能失常的作用。本研究旨在通过以下方法确定snoRNA在肺TIC中是否具有重要功能：1）分析和比较28例原发性NSCLC组织中肺ALDH 1 +/-细胞中snoRNA的表达模式，以确定TIC的新特征; 2）通过使用定量PCR分析82例不同分期和组织学类型的NSCLC组织中snoRNA的表达，确定snoRNA特征的预后意义; 3）使用体外和体内测定在功能上研究snoRNA是否有助于肺TIC的干性。鉴定了22种snoRNA，其变化对TIC具有特异性。两种snoRNA（snoRA 3和snoRA 42）的表达与NSCLC患者的生存率呈负相关（分别为P = 0.002，p = 0.001）。功能分析表明，与CD 133-对应物相比，snoRA 42在从NSCLC细胞系分离的CD 133+细胞中上调。snoRA 42基因敲低可降低体外培养的TIC的增殖和自我更新。然而，异位表达snoRA 42的非TIC细胞的增殖和自我更新的潜力增强。snoRA 42表达与肺TIC中干细胞核心转录因子的表达相关。阻断TIC异种移植物中的snoRA 42表达降低了小鼠的肿瘤发生。肺TIC的snoRNA特征为预测NSCLC的结果提供了潜在的生物标志物。snoRA 42是调节肺TIC特征的重要snoRNA之一，因此有助于肺肿瘤的发生。
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. 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. 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.
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影响因子：
3.7
作者：
Garzia L;Andolfo I;Cusanelli E;Marino N;Petrosino G;De Martino D;Esposito V;Galeone A;Navas L;Esposito S;Gargiulo S;Fattet S;Donofrio V;Cinalli G;Brunetti A;Vecchio LD;Northcott PA;Delattre O;Taylor MD;Iolascon A;Zollo M
通讯作者：
Zollo M
影响因子：
12.4
作者：
Eramo, A.;Lotti, F.;De Maria, R.
通讯作者：
De Maria, R.
影响因子：
3.4
作者：
Tirino, Virginia;Camerlingo, Rosa;Pirozzi, Giuseppe
通讯作者：
Pirozzi, Giuseppe
microRNA miR-34抑制人类胰腺癌肿瘤发射细胞。
影响因子：
3.7
作者：
Ji Q;Hao X;Zhang M;Tang W;Yang M;Li L;Xiang D;Desano JT;Bommer GT;Fan D;Fearon ER;Lawrence TS;Xu L
通讯作者：
Xu L
影响因子：
23.9
作者：
de Sousa e Melo, Felipe;Colak, Selcuk;Medema, Jan Paul
通讯作者：
Medema, Jan Paul