title: The PTTG1-targeting miRNAs miR-329, miR-300, miR-381, and miR-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/PTTG1 regulation feedback loop.
abstract: 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.
authors: Department of Neurosurgery, Pingjin Hospital, Logistics College of Armed Police Forces, Tianjin, China, 300162.
authors: Hai-qian
authors: HQ
authors: Liang
authors: Department of Neurosurgery, Pingjin Hospital, Logistics College of Armed Police Forces, Tianjin, China, 300162.
authors: Ren-jie
authors: RJ
authors: Wang
authors: Tianjin Saier-Biological Technology Company, Tianjin, China, 300353.
authors: Cai-feng
authors: CF
authors: Diao
authors: Department of Neurosurgery, Pingjin Hospital, Logistics College of Armed Police Forces, Tianjin, China, 300162.
authors: Jian-wei
authors: JW
authors: Li
authors: Department of Neurosurgery, Pingjin Hospital, Logistics College of Armed Police Forces, Tianjin, China, 300162.
authors: Jing-liang
authors: JL
authors: Su
authors: Department of Neurosurgery, Pingjin Hospital, Logistics College of Armed Police Forces, Tianjin, China, 300162.
authors: Sai
authors: S
authors: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064249:Securin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C000596512:MIRN300 microRNA, human; C584396:MIRN329 microRNA, human; C588249:MIRN381 microRNA, human; C585264:MIRN655 microRNA, human; D035683:MicroRNAs; D064249:Securin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C578002:pituitary tumor-transforming protein 1, human
keywords: PTTG1; miRNAs; p53; pituitary tumor