A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts
Data de publicació2012
Liu, Minzhi M.
Mendell, Joshua T.
Lupold, Shawn E.
MetadadesMostra el registre d'unitat complet
miR-21 is the most commonly over-expressed microRNA (miRNA) in cancer and a proven oncogene. Hsa-miR-21 is located on chromosome 17q23.2, immediately downstream of the vacuole membrane protein-1 (VMP1) gene, also known as TMEM49. VMP1 transcripts initiate ∼130 kb upstream of miR-21, are spliced, and
polyadenylated only a few hundred base pairs upstream of the miR-21 hairpin. On the other hand, primary miR-21 transcripts (pri-miR-21) originate within the last introns of VMP1, but bypass VMP1 polyadenylation signals to include the miR-21 hairpin. Here, we report that VMP1 transcripts can also bypass these polyadenylation signals to include miR-21, thus providing a novel and independently regulated source of miR-21, termed VMP1–miR-21. Northern blotting, gene-specific RT-PCR, RNA pull-down and DNA branching assays support that VMP1–miR-21 is expressed at significant levels in a number of cancer cell lines and that it is processed by the Microprocessor complex to produce mature miR-21. VMP1 and pri-miR-21 are induced by common stimuli, such as phorbol-12-myristate-13-acetate (PMA) and androgens, but show differential responses to some stimuli such as epigenetic modifying agents. Collectively, these results indicate that miR-21 is a unique miRNA capable of being regulated by alternative polyadenylation and two independent gene promoters.
És part deNucleic Acids Research, 2012, vol. 40, núm. 14, p. 6821-6833
Projectes de recerca europeus
Els fitxers de llicència següents estan associats amb aquest element:
Mostrant elements relacionats per títol, autor i matèria.
Investigation of miR-21, miR-141, and miR-221 expression levels in prostate adenocarcinoma for associated risk of recurrence after radical prostatectomy Zheng, Qizhi; Peskoe, Sarah B.; Ribas i Fortuny, Judit; Rafiqi, Fatema; Kudrolli, Tarana; Meeker, Alan K.; De Marzo, Angelo M.; Platz, Elizabeth A.; Lupold, Shawn E. (John Wiley & Sons, Inc., 2014-12)BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate a broad array of cellular and disease processes. Several miRNAs are differentially expressed in cancer and many are being considered as biomarkers for ...
Ni, Xiaohua; Zhang, Yonggang; Ribas i Fortuny, Judit; Chowdhury, Wasim H.; Castanares, Mark; Zhang, Zhewei; Laiho, Marikki; DeWeese, Theodore L.; Lupold, Shawn E. (American Society for Clinical Investigation, 2011)Dose-escalated radiation therapy for localized prostate cancer (PCa) has a clear therapeutic benefit; however, escalated doses may also increase injury to noncancerous tissues. Radiosensitizing agents can improve ...
The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors Landa, Iñigo; Ruiz-Llorente, Sergio; Montero-Conde, Cristina; Inglada-Pérez, Lucía; Schiavi, Francesca; Leskelä, Susanna; Pita, Guillermo; Milne, Roger; Maravall Royo, Javier; Ramos, Ignacio; Andía, Víctor; Rodríguez-Poyo, Paloma; Jara-Albarrán, Antonino; Meoro, Amparo; Peso, Cristina del; Arribas, Luis; Iglesias, Pedro; Caballero, Javier; Serrano, Joaquín; Picó, Antonio; Pomares, Francisco; Giménez, Gabriel; López-Mondéjar, Pedro; Castello, Roberto; Merante-Boschin, Isabella; Pelizzo, Maria-Rosa; Mauricio Puente, Dídac; Opocher, Giuseppe; Rodríguez-Antona, Cristina; González- Neira, Anna; Matias-Guiu, Xavier; Santisteban, Pilar; Robledo, Mercedes (Public Library of Science, 2009)In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and ...