title: Signature miRNAs in colorectal cancers were revealed using a bias reduction small RNA deep sequencing protocol.
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 up-regulated 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.
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Guihua
authors.initials: G
authors.lastname: Sun
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.affiliation: Department of Surgery, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Lily
authors.initials: L
authors.lastname: Lai
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tsui-Chin
authors.initials: TC
authors.lastname: Huang
authors.affiliation: Integrated Genome Core, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Integrated Genome Core, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Yafan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Yasheng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Jinghan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.
authors.forename: Shuya
authors.initials: S
authors.lastname: Hu
authors.affiliation: Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ji-Rui
authors.initials: JR
authors.lastname: Yang
authors.affiliation: Department of Molecular Pharmacology, Beckman Research Institute of The City of Hope, Duarte, CA, USA.|Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: colorectal cancer; miR-143; miR-21; microRNA; small RNA deep sequencing