SNORA21 - An Oncogenic Small Nucleolar RNA, with a Prognostic Biomarker Potential in Human Colorectal Cancer.
SNORA21 - An Oncogenic Small Nucleolar RNA, with a Prognostic Biomarker Potential in Human Colorectal Cancer.
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DOI：
10.1016/j.ebiom.2017.07.009
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发表时间：
2017-08
期刊：
影响因子：
11.1
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Yoshida K;Toden S;Weng W;Shigeyasu K;Miyoshi J;Turner J;Nagasaka T;Ma Y;Takayama T;Fujiwara T;Goel A
越来越多的证据表明，小核仁RNA(SnoRNAs)在肿瘤发生中起着核心作用。在此，我们系统地评估了snoRNAs在结直肠癌(CRC)中的表达谱，并研究了它们在这种恶性肿瘤中的临床和功能作用。我们使用公开可用的数据集比较了snoRNAs在肿瘤组织和正常组织中的表达水平，并确定了在结直肠癌中差异表达最多、通常上调最多的snoRNAs。这些结果在489个大肠组织中进行了检测，以评估其临床意义，随后进行了一系列体外和体内实验，以评估候选snoRNAs的功能作用。使用多个RNA图谱数据集，我们发现SNORA21在结直肠癌中持续过表达。在临床验证队列中，SNORA21在结直肠腺瘤和癌症中的表达水平上调。此外，SNORA21升高成为预测预后不良的独立因素。体外和体内实验表明，CRISPR/Cas9介导的抑制SNORA21表达通过调节多条肿瘤相关途径而导致细胞增殖和侵袭能力下降。我们系统地确定SNORA21是结直肠癌中一个关键的致癌snoRNA，它在结直肠癌的发展过程中起着重要的作用，并可能作为结直肠癌重要的预后生物标志物。系统的综合分析表明，SNORA21在结直肠癌中显著上调。SNONA21表达升高与结直肠癌的转移有关，并预示着预后不良。SNORA21是一种有前景的肿瘤预后生物标志物，也是结直肠癌治疗的潜在靶点。新的证据表明，小核仁RNAs(SnoRNAs)可能在肿瘤发生中起核心作用；然而，snoRNAs在结直肠癌(CRC)中的临床意义和功能作用尚不清楚。在此，我们利用多个公开可用的数据集，系统地评估了snoRNAs在结直肠癌中的表达情况，并阐明了SNORA21的高表达与远处转移和总体生存不良有关。一系列体外和体内实验揭示了SNORA21的致癌作用。我们的研究结果表明，SNORA21是一个很有前途的肿瘤预后生物标志物，也是结直肠癌潜在的治疗靶点。
Emerging evidence indicates that small nucleolar RNAs (snoRNAs) play a central role in oncogenesis. Herein, we systematically evaluated expression profiles of snoRNAs in colorectal cancer (CRC) and investigated their clinical and functional role in this malignancy. We compared expression levels of snoRNAs between cancer and normal tissues using publicly available datasets and identified the most differentially expressed and commonly upregulated snoRNAs in CRC. These results were examined in 489 colorectal tissues to assess their clinical significance, followed by a series of in vitro and in vivo experiments to evaluate the functional role of candidate snoRNAs. Using multiple RNA profiling datasets, we identified consistent overexpression of SNORA21 in CRC. In the clinical validation cohorts, the expression level of SNORA21 was upregulated in colorectal adenomas and cancers. Furthermore, elevated SNORA21 emerged as an independent factor for predicting poor survival. Both in vitro and in vivo experiments revealed that CRISPR/Cas9-mediated inhibition of SNORA21 expression resulted in decreased cell proliferation and invasion through modulation of multiple cancer related pathways. We systematically identified SNORA21 as a key oncogenic snoRNA in CRC, which plays an important role in cancer progression, and might serve as an important prognostic biomarker in CRC. Systematic and comprehensive analysis revealed that SNORA21 was significantly upregulated in CRC. Elevated SNONA21 expression was related to metastasis and predicted poor prognosis in CRC patients. SNORA21 is a promising cancer prognostic biomarker and a potential therapeutic target in CRC. Emerging evidence indicates that small nucleolar RNAs (snoRNAs) might play a central role in oncogenesis; however, the clinical significance and functional roles of snoRNAs in colorectal cancer (CRC) remain unclear. Herein, using multiple publicly available datasets, we systematically assessed expression profiles of snoRNAs in CRC and elucidated that the high expression of SNORA21 was associated with distant metastasis and poor overall survival. A series of in vitro and in vivo experiments revealed oncogenic role for SNORA21. Our findings indicate that SNORA21 is a promising cancer prognostic biomarker and a potential therapeutic target in CRC.
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影响因子：
24.5
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通讯作者：
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