Kallikreins as microRNA targets: an in silico and experimental-based analysis.
microRNAs (miRNAs) are non-coding RNAs that target specific mRNAs. They have been shown to control many biological processes including cancer pathogenesis. Kallikreins (KLKs) are a family of serine proteases that are attracting interest as cancer biomarkers. The mechanism of regulation of kallikrein expression is largely unknown. We investigated the potential roles of miRNAs in regulating KLK expression. Using a bioinformatics approach, we identified 96 strong KLK/miRNA interactions. KLK10 is the most frequently targeted kallikrein, followed by KLK5 and KLK13. KLK1, KLK3, KLK8 and KLK12 do not have strongly predicted miRNA/KLK interactions. Ten miRNAs are predicted to target more than one KLK. KLK2, KLK4, KLK5 and KLK10 have multiple miRNA-targeting sites on their transcript. Chromosomes 19 and 14 harbor significantly more KLK-targeting miRNAs. Many KLK-targeting miRNAs have been shown to be dysregulated in malignancy. We experimentally verified our bioinformatics data for the let-7f miRNA in a cell line model. let-7f transfection led to a significant decrease in secreted KLK6 and KLK10 protein levels. Co-transfection of let-7f and anti-let-7f inhibitor was able to partially rescue these protein levels. We conclude that miRNAs play a role in the regulation of KLK expression. Further studies are needed to investigate whether this regulation is altered in cancer.
Chow
Tsz-fung F
TF
Department of Laboratory Medicine, and the Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto M5B 1W8, Canada.
Crow
Megan
M
Earle
Tammy
T
El-Said
Hala
H
Diamandis
Eleftherios P
EP
Yousef
George M
GM
D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002877:Chromosomes, Human / Q000378:metabolism; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014162:Transfection
D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; D007610:Kallikreins