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1. SNORA21 – An Oncogenic Small Nucleolar RNA, with a Prognostic Biomarker Potential in Human Colorectal Cancer

Author

Kazuhiro Yoshida, Shusuke Toden, Wenhao Weng, Kunitoshi Shigeyasu, Jinsei Miyoshi, Jacob Turner, Takeshi Nagasaka, Yanlei Ma, Tetsuji Takayama, Toshiyoshi Fujiwara, and Ajay Goel

Subjects
snoRNA, SNORA21, Distant metastasis, Prognostic marker, Colorectal cancer, Medicine, Medicine (General), R5-920
Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Published
2017
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2. SNORA21 – An Oncogenic Small Nucleolar RNA, with a Prognostic Biomarker Potential in Human Colorectal Cancer

Author

Jinsei Miyoshi, Jacob Turner, Takeshi Nagasaka, Shusuke Toden, Yanlei Ma, Wenhao Weng, Kazuhiro Yoshida, Ajay Goel, Tetsuji Takayama, Kunitoshi Shigeyasu, and Toshiyoshi Fujiwara

Subjects
Male, 0301 basic medicine, Colorectal cancer, lcsh:Medicine, Bioinformatics, medicine.disease_cause, Mice, AUC, area under the curve, 0302 clinical medicine, Prognostic marker, Databases, Genetic, GEO, Gene Expression Omnibus, Small nucleolar RNA, GO, Gene ontology, TNM, The tumor-node-metastasis, Aged, 80 and over, snoRNAs, small nucleolar RNAs, lcsh:R5-920, ncRNAs, non-coding RNAs, pCRC, primary colorectal cancer, General Medicine, Middle Aged, Prognosis, Up-Regulation, 3. Good health, Gene Expression Regulation, Neoplastic, FFPE, formalin-fixed paraffin-embedded, Real-time polymerase chain reaction, 030220 oncology & carcinogenesis, CRC, colorectal cancer, Distant metastasis, Female, 95% CI, 95% confidence interval, NM, normal mucosa, Colorectal Neoplasms, CRISPR/Cas9, Clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9, lcsh:Medicine (General), Research Paper, Adult, rRNAs, ribosomal RNAs, FDR, false discovery rate, qRT-PCR, quantitative reverse transcription polymerase chain reaction, ROC, Receiver operating characteristic, SNORA21, Biology, Malignancy, snoRNA, KEGG, Kyoto Encyclopedia of Genes and Genomes, General Biochemistry, Genetics and Molecular Biology, OS, overall survival, 03 medical and health sciences, Cell Line, Tumor, microRNA, Biomarkers, Tumor, medicine, Animals, Humans, RNA, Small Nucleolar, miRNAs, microRNAs, Neoplasm Invasiveness, KEGG, Aged, Cell Proliferation, urogenital system, Gene Expression Profiling, lncRNAs, long non-coding RNAs, lcsh:R, sgRNA, single guide RNA, LM, liver metastasis, HCT116 Cells, medicine.disease, Survival Analysis, HR, hazard ratio, Gene expression profiling, 030104 developmental biology, Cancer research, TCGA, The Cancer Genome Atlas, snoRNPs, small nucleolar ribosonucleoproteins, Caco-2 Cells, Carcinogenesis, Neoplasm Transplantation
Abstract

Background 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. Methods 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. Results 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. Conclusions 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., Highlights • 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.

Published
2017

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