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

Cancer Cell International

Abraham Silva-Carmona¹  Jossimar Coronel-Hernández²  Eduardo López-Urrutia²  Carlos Pérez-Plasencia²  Izamary Delgado-Waldo²  Carlos Contreras-Romero²  Alma D. Campos-Parra³  Miguel Rodríguez-Morales³  Rebeca Salgado-García³  Gabriela Figueroa-González³  Antonio Martínez-Gutierrez³  Luis Ignacio Terrazas⁴  César López-Camarillo⁵  Nadia Jacobo-Herrera⁶ 

[1] Laboratorio de Genética, Genómica y Bioinformática, Hospital Infantil de México;Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM;Laboratorio de Genómica, Instituto Nacional de Cancerología;Laboratorio de Inmunología de Parásitos, Unidad de Biomedicina, FES-IZTACALA, UNAM;Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México;Unidad de Bioquímica, Instituto de Ciencias Médicas y Nutrición, Salvador Zubirán;

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

DOI  :  10.1186/s12935-019-0802-5

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown