4 years ago

miRNA arm switching identifies novel tumour biomarkers

Liang Chen, Huiyan Sun, Changliang Wang, Yang Yang, Menglei Zhang, Garry Wong

Publication date: Available online 10 November 2018

Source: EBioMedicine

Author(s): Liang Chen, Huiyan Sun, Changliang Wang, Yang Yang, Menglei Zhang, Garry Wong

Abstract
Background

microRNAs have been reported to play critical roles in cancer and to have potential as diagnostic biomarkers. During miRNA biogenesis, one strand of the miRNA hairpin precursor is preferentially selected as a functionally mature miRNA, while the other strand is typically degraded. Arm switching occurs when the strand preference is changed. This preference can be different and can change dynamically depending upon the species, tissue types, or development stages. Due to recent advances in next-generation sequencing methods, arm switching has been observed in a variety of cancers.

Methods

A tumour miRNA-Seq dataset was collected from The Cancer Genome Atlas (TCGA). The support vector machine (SVM) method combined with 5-fold cross validation was applied to select the best combination of arm-switched miRNA tumour markers. Survival analysis was also applied to identify patient survival associated miRNA markers.

Findings

We observed 51 arm-switched miRNAs and of these, 7 were associated with patient survival. Twenty-three 1-combination arm switching miRNAs with excellent diagnostic value were identified. Interestingly, ovarian cancer showed a significant difference in arm switching pattern compared with 32 other cancers.

Interpretation

These results suggest that arm switching miRNAs could be used as potential biomarkers for various cancers.

Fund

This work was partially supported by the National Natural Science Foundation of China (no. 61472158, 61572227), and University of Macau Faculty of Health Sciences ( MYRG2016-00101-FHS).

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