Next Article in Journal
Transcriptome Analysis Identifies a 140 kb Region of Chromosome 3B Containing Genes Specific to Fusarium Head Blight Resistance in Wheat
Next Article in Special Issue
MicroRNAs Targeting Caspase-3 and -7 in PANC-1 Cells
Previous Article in Journal
Barcoded Pyrosequencing Reveals a Shift in the Bacterial Community in the Rhizosphere and Rhizoplane of Rehmannia glutinosa under Consecutive Monoculture
Previous Article in Special Issue
Luminal lncRNAs Regulation by ERα-Controlled Enhancers in a Ligand-Independent Manner in Breast Cancer Cells
Open AccessArticle

A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma

1
Department of Pathology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
2
Medical Student Research Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(3), 851; https://doi.org/10.3390/ijms19030851
Received: 24 January 2018 / Revised: 8 March 2018 / Accepted: 13 March 2018 / Published: 14 March 2018
MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation of RNA followed by sequencing (CLIP-seq) have enabled transcriptome-wide identification of miRNA interactomes. In our study, we use a publicly available Argonaute-CLIP dataset (GSE97061), which contains nine HCC cases with matched benign livers, to characterize the miR-21 interactome in HCC. Argonaute-CLIP identified 580 miR-21 bound target sites on coding transcripts, of which 332 were located in the coding sequences, 214 in the 3′-untranslated region, and 34 in the 5′-untranslated region, introns, or downstream sequences. We compared the expression of miR-21 targets in 377 patients with liver cancer from the data generated by The Cancer Genome Atlas (TCGA) and found that mRNA levels of 402 miR-21 targets are altered in HCC. Expression of three novel predicted miR-21 targets (CAMSAP1, DDX1 and MARCKSL1) correlated with HCC patient survival. Analysis of RNA-seq data from SK-Hep1 cells treated with a miR-21 antisense oligonucleotide (GSE65892) identified RMND5A, an E3 ubiquitin ligase, as a strong miR-21 candidate target. Collectively, our analysis identified novel miR-21 targets that are likely to play a causal role in hepatocarcinogenesis. View Full-Text
Keywords: miRNA; miR-21; liver cancer; HCC miRNA; miR-21; liver cancer; HCC
Show Figures

Graphical abstract

MDPI and ACS Style

Koenig, A.B.; Barajas, J.M.; Guerrero, M.J.; Ghoshal, K. A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma. Int. J. Mol. Sci. 2018, 19, 851.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop