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Deregulation of the pituitary tumor transforming gene (PTTG1), a newly discovered oncogene, is a hallmark of various malignancies, including pituitary tumors. However, the mechanisms regulating PTTG1 expression are still needed to be explored. MicroRNAs (miRNAs) are a novel class of small RNA molecules that act as posttranscriptional regulators of gene expression and can play a significant role in tumor development. Here, we identified a series of miRNAs, namely, miR-329, miR-300, miR-381 and miR-655, which could target PTTG1 messenger RNA and inhibit its expression. Interestingly, all four miRNAs significantly that are downregulated in pituitary tumors were mapped to the 14q32.31 locus, which acts as a tumor suppressor in several cancers. Functional studies show that the PTTG1-targeting miRNAs inhibit proliferation, migration and invasion but induce apoptosis in GH3 and MMQ cells. Furthermore, overexpression of a PTTG1 expression vector lacking the 3′UTR partially reverses the tumor suppressive effects of these miRNAs. Next, we identified the promoter region of PTTG1-targeting miRNAs with binding sites for p53. In our hands, p53 transcriptionally activated the expression of these miRNAs in pituitary tumor cells. Finally, we found that PTTG1 could inhibit p53 transcriptional activity to the four miRNAs. These data indicate the existence of a feedback loop between PTTG1 targeting miRNAs, PTTG1 and p53 that promotes pituitary tumorigenesis. Together, these findings suggest that these PTTG1-targeting miRNAs are important players in the regulation of pituitary tumorigenesis and that these miRNAs may serve as valuable therapeutic targets for cancer treatment.

Increasing evidence has lent support to the notion that miRNAs regulate hepatocellular carcinoma (HCC) cell proliferation by directly targeting cell cycle-related genes. Among these genes, we identified PRPF4B, a CDK-like kinase, as a new target of miR-371-5p. Over-expression of miR-371-5p and knockdown of PRPF4B promotes cell growth by accelerating the G1/S transition in HCC cell lines. Moreover, miR-371-5p promotes tumor growth of QGY-7703 cells in vivo. Conversely, inhibition of miR-371-5p yields an opposing effect. Ectopic expression of PFPF4B abolishes the malignant phenotypes caused by miR-371-5p. Furthermore, contrary to PRPF4B, miR-371 was up-regulated in HCC tissues. Collectively, we highlight the significance of miR-371-5p and PRPF4B in cell cycle progression and hepatocarcinogenesis.