Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells

被引:81
作者
Peralta-Zaragoza, Oscar [1 ]
Deas, Jessica [1 ]
Meneses-Acosta, Angelica [3 ]
De la O-Gomez, Faustino [1 ]
Fernandez-Tilapa, Gloria [2 ]
Gomez-Ceron, Claudia [1 ]
Benitez-Boijseauneau, Odelia [1 ]
Burguete-Garcia, Ana [1 ]
Torres-Poveda, Kirvis [1 ,7 ]
Hugo Bermudez-Morales, Victor [1 ]
Madrid-Marina, Vicente [1 ]
Rodriguez-Dorantes, Mauricio [4 ]
Hidalgo-Miranda, Alfredo [4 ]
Perez-Plasencia, Carlos [5 ,6 ]
机构
[1] Natl Inst Publ Hlth, Res Ctr Infect Dis, Direct Chron Infect & Canc, Ave Univ 655, Cuernavaca 62100, Morelos, Mexico
[2] Guerrero Autonomous Univ, Acad Unit Biol Chem Sci, Clin Res Lab, Ave Lazaro Cardenas S-N, Chilpancingo 39070, Guerrero, Mexico
[3] Autonomous Univ Morelos State, Fac Pharm, Pharmaceut Biotechnol Lab, Ave Univ 1001, Cuernavaca 62010, Morelos, Mexico
[4] Natl Inst Genom Med, Perifer Sur 4809, Mexico City 14610, DF, Mexico
[5] Natl Canc Inst Mexico, Oncogen Lab, Ave San Fernando 22,Colonia Secc 16, Mexico City 14080, DF, Mexico
[6] FES Iztacala UNAM, Biomed Unit, Av los Barrios S-N, Tlalnepantla De Baz 54090, Estado De Mexic, Mexico
[7] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico
关键词
Cervical cancer; microRNAs; miR-21; PTEN; siRNAs; HUMAN GLIOBLASTOMA CELLS; MICRORNA-21; TARGETS; HUMAN PAPILLOMAVIRUSES; LUNG-CANCER; RT-PCR; EXPRESSION; INVASION; GROWTH; CARCINOMA; APOPTOSIS;
D O I
10.1186/s12885-016-2231-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:16
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