Tracking miR-17-5p Levels following Expression of Seven Reported Target mRNAs

SIMPLE SUMMARY: MicroRNAs (miRNAs) are non-coding RNA sequences that promote gene silencing by targeting matching mRNAs. miR-17-5p is a typical oncogenic miRNA overexpressed in many types of cancers. Due to imperfect specificity, a single miRNA, such as miR-17-5p, may target multiple mRNAs with a range of tissue-specific effects. Therefore, investigating miRNA functions is rather complex. In this study, miR-17-5p was found to be correlated with and modulated by the tested miR-17-5p downstream target mRNA levels in cancer cell lines, suggesting that these target mRNA levels may play roles in stabilizing and modifying the expression of miR-17-5p. We postulate that the mechanisms regulating miR-17-5p expression by its known target transcripts can provide an understanding of the dysregulated expression and functions of miRNAs in cancer progression. ABSTRACT: As the most prominent member of the miR-17-92 cluster, miR-17-5p is well associated with tumorigenesis and cancer progression. It can exert both oncogenic and tumor-suppressive functions by inducing translational repression and/or mRNA decay. The complexity of the tissue-specific expression of the targeted transcripts seems to contribute to the differential functions of miR-17-5p in different types of cancers. In this study, we selected 12 reported miR-17-5p targeting genes with mRNA levels unaffected by miR-17-5p expression and analyzed their expression in 31 organ tissues in transgenic mice by real-time PCR. Surprisingly, miR-17-5p expressing transgenic mice showed a positive correlation in these tissues between miR-17-5p expression levels and the selected miR-17-5p targeted transcripts; with high expression of the miRNA in organs with high selected miRNA-targeted mRNA levels. In cancer cell lines, overexpression of 7 reported miR-17-5p targeted genes’ 3′-UTRs promoted miR-17-5p expression; meanwhile, transfection of 3′-UTRs with mutations had no significant effect. Moreover, an increase in AGO2 mRNA was associated with 3′-UTR expression as confirmed by real-time PCR. Hence, miR-17-5p regulation by these target genes might be an alternative mechanism to maintain miR-17-5p expression at tissue-specific levels.