title: Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells.
abstract: BACKGROUND
  Expression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells.
  
  
  METHODS
  To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction.
  
  
  RESULTS
  In SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3'-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction.
  
  
  CONCLUSIONS
  We conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential therapeutic target in gene therapy for cervical cancer.
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico. operalta@insp.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peralta-Zaragoza
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Jessica
authors.initials: J
authors.lastname: Deas
authors.affiliation: Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Autonomous University of Morelos State, Avenida Universidad No. 1001, Cuernavaca, Morelos, México, 62010, Mexico.
authors.forename: Angélica
authors.initials: A
authors.lastname: Meneses-Acosta
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Faustino
authors.initials: F
authors.lastname: De la O-Gómez
authors.affiliation: Clinical Research Laboratory, Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Avenida Lázaro Cárdenas S/N, Col. Haciendita, Chilpancingo, Guerrero, México, 39070, Mexico.
authors.forename: Gloria
authors.initials: G
authors.lastname: Fernández-Tilapa
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: Gómez-Cerón
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Odelia
authors.initials: O
authors.lastname: Benítez-Boijseauneau
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Ana
authors.initials: A
authors.lastname: Burguete-García
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.|CONACyT Research Fellow-Instituto Nacional de Salud Pública (INSP), Cuernavaca, Morelos, Mexico.
authors.forename: Kirvis
authors.initials: K
authors.lastname: Torres-Poveda
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Victor Hugo
authors.initials: VH
authors.lastname: Bermúdez-Morales
authors.affiliation: Direction of Chronic Infections and Cancer, Research Center in Infection Diseases, National Institute of Public Health, Av. Universidad No. 655, Cerrada los Pinos y Caminera, Colonia Santa María Ahuacatitlán, Cuernavaca, Morelos, México, 62100, Mexico.
authors.forename: Vicente
authors.initials: V
authors.lastname: Madrid-Marina
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan, México, D.F., C.P. 14610, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rodríguez-Dorantes
authors.affiliation: National Institute of Genomic Medicine, Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan, México, D.F., C.P. 14610, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Hidalgo-Miranda
authors.affiliation: Oncogenomics Laboratory, National Cancer Institute of Mexico, Tlalpan, Av. San Fernando No. 22, Colonia Sección XVI, Delegación Tlalpan, Distrito Federal, México, 14080, Mexico.|Biomedicine Unit, FES-Iztacala UNAM, Av. De los Barrios S/N. Colonia Los Reyes Iztacala, Tlalnepantla de Baz, Estado de México, 54090, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Plasencia
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Cervical cancer; PTEN; miR-21; microRNAs; siRNAs