Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol

Guihua Sun, Ya Wen Cheng, Lily Lai, Tsui Chin Huang, Jinhui Wang, Xiwei Wu, Yafan Wang, Yasheng Huang, Jinghan Wang, Keqiang Zhang, Shuya Hu, Ji Rui Yang, Yun Yen

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

To explore the role of miRNAs in colorectal cancers (CRC), we have deep sequenced 48 pairs of frozen CRC samples, of which 44 pairs produced high quality sequencing data. By using a combined approach of our bias reduction small RNA (smRNA) deep sequencing protocol and Illumina small RNA TruSeq method for sample bar coding, we have obtained data from samples of relatively large size with bias reduced digital profile results. This novel approach allowed us to validate many previously published results using various techniques to profile miRNAs in CRC tissues or cell lines and to characterize 'true' miRNA signatures highly expressed in colon/ rectum (CR) or CRC tissues. According to our results, miR-21, a miRNA that is upregulated in CRC, and miR-143, a miRNA that is down-regulated in CRC, are the two miRNAs that dominated the miRNA population in CR tissues, and probably are also the most important miRNAs in CRCs. These two miRNAs, together with the other eight miRNAs, miR-148a, -194, -192, 200b, -200c, -10b, -26a, and -145, with descending expressing levels, constituted the top 10 highly expressed miRNAs in CR/CRC. Using TaqMan miRNA qPCR, we detected the relative expression of some of the CRC miRNAs in 10 CRC cell lines, validated their dysregulation under cancer condition, and provided possible explanation for their dysregulation, which could be caused by APC, KRAS, or TP53 mutations. We believe these results will provide a new direction in future miRNA-related CRC development studies, and application of miRNAs in CRC diagnosis/ prognosis, and therapy.

Original languageEnglish
Pages (from-to)3857-3872
Number of pages16
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 2016

Keywords

  • Colorectal cancer
  • MicroRNA
  • miR-143
  • miR-21
  • Small RNA deep sequencing

ASJC Scopus subject areas

  • Oncology

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