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Cancer Cell Int. 2019 Apr 2;19:80. doi: 10.1186/s12935-019-0802-5. eCollection 2019.

Cell migration and proliferation are regulated by miR-26a in colorectal cancer via the PTEN-AKT axis.

Author information

1
1Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico.
2
7Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
3
2Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Zip code 14080 Mexico City, DF Mexico.
4
Unidad de Bioquímica, Instituto de Ciencias Médicas y Nutrición, Salvador Zubirán, Tlalpan, Mexico City, DF Mexico.
5
4Laboratorio de Inmunología de Parásitos, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico.
6
5Laboratorio de Genética, Genómica y Bioinformática, Hospital Infantil de México, Mexico City, Mexico.
7
6Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico.
#
Contributed equally

Abstract

Background:

Invasion and metastasis are determinant events in the prognosis of Colorectal cancer (CRC), a common neoplasm worldwide. An important factor for metastasis is the acquired capacity of the cell to proliferate and invade adjacent tissues. In this paper, we explored the role of micro-RNA-26a in the regulation of proliferation and migration in CRC-derived cells through the negative regulation of PTEN, a key negative regulator of the AKT pathway.

Methods:

Expression levels of PTEN and mir-26a were surveyed in normal and CRC-derived cell lines; paraffin embedded human tissues, TCGA CRC expression data and a Balb/c mice orthotopic induced CRC model. CRC was induced by an initial intraperitoneal dose of the colonic carcinogen Azoxymethane followed by inflammatory promoter Dextran Sulfate Sodium Salt. Luciferase assays provide information about miR-26a-PTEN 3'UTR interaction. Proliferation and migration by real time cell analysis and wound-healing functional analyses were performed to assess the participation of mir-26a on important hallmarks of CRC and its regulation on the PTEN gene.

Results:

We observed a negative correlation between PTEN and mir-26a expression in cell lines, human tissues, TCGA data, and tissues derived from the CRC mouse model. Moreover, we showed that negative regulation of PTEN exerted by miR-26a affected AKT phosphorylation levels directly. Functional assays showed that mir-26a directly down-regulates PTEN, and that mir-26a over-expressing cells had higher proliferation and migration rates.

Conclusions:

All this data proposes an important role of mir-26a as an oncomir in the progression and invasion of CRC. Our data suggested that mir-26a could be used as a biomarker of tumor development in CRC patients, however more studies must be conducted to establish its clinical role.

KEYWORDS:

AKT; Animal model for carcinogenesis; Colorectal cancer; MicroRNA; PTEN; mir-26a

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