1. Department of Pharmacy, Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan
2. Department of Pharmacy, China Medical University, Taichung, Taiwan
3. Department of Colorectal Surgery, China Medical University Hospital, Taichung, Taiwan
4. Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan
5. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
6. Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan
7. Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan
8. Department of Nursing, Asia University, Taichung, Taiwan
* Jiunn-Bey Pao and Te-Ling Lu contributed equally to this work.
Background: Single nucleotide polymorphisms (SNPs) of small non-coding RNAs (sncRNAs) can influence sncRNA function and target gene expression to mediate the risk of certain diseases. The aim of the present study was to evaluate the prognostic relevance of sncRNA SNPs for colorectal cancer, which has not been well characterized to date.
Methods: We comprehensively examined 31 common SNPs of sncRNAs, and assessed the impact of these variants on survival in a cohort of 188 patients with colorectal cancer.
Results: Three SNPs were significantly associated with survival of patients with colorectal cancer after correction for multiple testing, and two of the SNPs (hsa-mir-196a-2 rs11614913 and U85 rs714775) remained significant in multivariate analyses. Additional in silico analysis provided further evidence of this association, since the expression levels of the target genes of the hsa-miR-196a (HOXA7, HOXB8, and AKT1) were significantly correlated with colorectal cancer progression. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that hsa-miR-196a is associated with well-known oncogenic pathways, including cellular protein modification process, mitotic cell cycle, adherens junction, and extracellular matrix receptor interaction pathways.
Conclusion: Our results suggest that SNPs of sncRNAs could play a critical role in cancer progression, and that hsa-miR-196a might be a valuable biomarker or therapeutic target for colorectal cancer patients.
Keywords: colorectal cancer, survival, small non-coding RNA, single nucleotide polymorphism, biomarker