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BMC Cancer. 2016 Mar 14;16:215. doi: 10.1186/s12885-016-2231-3.

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

Author information

1
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.
2
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.
3
Pharmaceutical Biotechnology Laboratory, Faculty of Pharmacy, Autonomous University of Morelos State, Avenida Universidad No. 1001, Cuernavaca, Morelos, México, 62010, Mexico.
4
Clinical Research Laboratory, Academic Unit of Biological Chemical Sciences, Guerrero Autonomous University, Avenida Lázaro Cárdenas S/N, Col. Haciendita, Chilpancingo, Guerrero, México, 39070, Mexico.
5
CONACyT Research Fellow-Instituto Nacional de Salud Pública (INSP), Cuernavaca, Morelos, Mexico.
6
National Institute of Genomic Medicine, Periférico Sur No. 4809, Col. Arenal Tepepan, Delegación Tlalpan, México, D.F., C.P. 14610, Mexico.
7
Oncogenomics Laboratory, National Cancer Institute of Mexico, Tlalpan, Av. San Fernando No. 22, Colonia Sección XVI, Delegación Tlalpan, Distrito Federal, México, 14080, Mexico.
8
Biomedicine Unit, FES-Iztacala UNAM, Av. De los Barrios S/N. Colonia Los Reyes Iztacala, Tlalnepantla de Baz, Estado de México, 54090, Mexico.

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.

KEYWORDS:

Cervical cancer; PTEN; miR-21; microRNAs; siRNAs

PMID:
26975392
PMCID:
PMC4791868
DOI:
10.1186/s12885-016-2231-3
[Indexed for MEDLINE]
Free PMC Article

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