Genes & Cancer

MicroRNA-messenger RNA interactions involving JAK-STAT signaling genes in colorectal cancer

Lila E. Mullany1, Jennifer S. Herrick1, Lori C. Sakoda2, Wade Samowitz3, John R. Stevens4, Roger K. Wolff1 and Martha L. Slattery1

1 Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, Utah

2 Division of Research, Kaiser Permanente Northern California, Oakland, California

3 Department of Pathology, University of Utah, Salt Lake City, Utah

4 Department of Mathematics and Statistics, Utah State University, Logan, Utah


Lila E. Mullany, email:

Keywords: colorectal; cancer; JAK-STAT; miRNA; receptor

Received: July 05, 2018 Accepted: August 29, 2018 Published: September 07, 2018


JAK-STAT signaling influences many downstream processes that, unchecked, contribute to carcinogenesis and metastasis. MicroRNAs (miRNAs) are hypothesized as a mechanism to prevent uncontrolled growth from continuous JAK-STAT activation. We investigated differential expression between paired carcinoma and normal colorectal mucosa of messenger RNAs (mRNAs) and miRNAs using RNA-Seq and Agilent Human miRNA Microarray V19.0 data, respectively, using a negative binomial mixed effects model to test 122 JAK-STAT-signaling genes in 217 colorectal cancer (CRC) cases. Overall, 42 mRNAs were differentially expressed with a fold change of >1.50 or <0.67, remaining significant with a false discovery rate of < 0.05; four were dysregulated in microsatellite stable (MSS) tumors, eight were for microsatellite unstable (MSI)-specific tumors. Of these 54 mRNAs, 17 were associated with differential expression of 46 miRNAs, comprising 116 interactions: 16 were significant overall, one for MSS tumors only. Twenty of the 29 interactions with negative beta coefficients involved miRNA seed sequence matches with mRNAs, supporting miRNA-mediated mRNA repression; 17 of these mRNAs encode for receptor molecules. Receptor molecule degradation is an established JAK-STAT signaling control mechanism; our results suggest that miRNAs facilitate this process. Interactions involving positive beta coefficients may illustrate downstream effects of disrupted STAT activity, and subsequent miRNA upregulation.

PII: 177