Cell migration and proliferation are regulated by miR-26a in colorectal cancer via the PTEN-AKT axis
Por:
Coronel-Hernandez, Jossimar, Lopez-Urrutia, Eduardo, Contreras-Romero, Carlos, Delgado-Waldo, Izamary, Figueroa-Gonzalez, Gabriela, Campos-Parra, Alma D., Salgado-Garcia, Rebeca, Martinez-Gutierrez, Antonio, Rodriguez-Morales, Miguel, Jacobo-Herrera, Nadia, Terrazas L.I., Silva-Carmona, Abraham, Lopez-Camarillo, Cesar, Perez-Plasencia, Carlos
Publicada:
1 ene 2019
Resumen:
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. © 2019 The Author(s).
Filiaciones:
Coronel-Hernandez, Jossimar:
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
UNAM, Unidad Biomed, Lab Genom Func, FES,IZTACALA, Tlalnepantla, Mexico
Univ Nacl Autonoma Mexico, Programa Doctorado Ciencias Biomed, Mexico City, DF, Mexico
Lopez-Urrutia, Eduardo:
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
UNAM, Unidad Biomed, Lab Genom Func, FES,IZTACALA, Tlalnepantla, Mexico
Contreras-Romero, Carlos:
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
UNAM, Unidad Biomed, Lab Genom Func, FES,IZTACALA, Tlalnepantla, Mexico
Delgado-Waldo, Izamary:
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
UNAM, Unidad Biomed, Lab Genom Func, FES,IZTACALA, Tlalnepantla, Mexico
Figueroa-Gonzalez, Gabriela:
Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Mexico City DF, Zip code 14080, Mexico
Inst Nacl Cancerol, Lab Genom, Av San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico
Campos-Parra, Alma D.:
Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Mexico City DF, Zip code 14080, Mexico
Inst Nacl Cancerol, Lab Genom, Av San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico
Salgado-Garcia, Rebeca:
Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Mexico City DF, Zip code 14080, Mexico
Inst Nacl Cancerol, Lab Genom, Av San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico
Martinez-Gutierrez, Antonio:
Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Mexico City DF, Zip code 14080, Mexico
Inst Nacl Cancerol, Lab Genom, Av San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico
Rodriguez-Morales, Miguel:
Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Mexico City DF, Zip code 14080, Mexico
Inst Nacl Cancerol, Lab Genom, Av San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico
Jacobo-Herrera, Nadia:
Unidad de Bioquímica, Instituto de Ciencias Médicas y Nutrición, Salvador-Zubirán-Tlalpan-Mexico-City-DF, Mexico
Inst Ciencias Med & Nutr, Unidad Bioquim, Mexico City, DF, Mexico
Terrazas L.I.:
Laboratorio de Inmunología de Parásitos, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
Silva-Carmona, Abraham:
Laboratorio de Genética, Genómica y Bioinformática, Hospital Infantil de México, Mexico City, Mexico
Hosp Infantil Mexico Dr Federico Gomez, Lab Genet Genom & Bioinformat, Mexico City, DF, Mexico
Lopez-Camarillo, Cesar:
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico
Univ Autonoma Ciudad Mexico, Posgrad Ciencias Genom, Mexico City, DF, Mexico
Perez-Plasencia, Carlos:
Laboratorio de Genómica Funcional, Unidad de Biomedicina, FES-IZTACALA, UNAM, Tlalnepantla, Mexico
Laboratorio de Genómica, Instituto Nacional de Cancerología, Av. San Fernando No 22, Col. Sección XVI, Tlalpan, Mexico City DF, Zip code 14080, Mexico
UNAM, Unidad Biomed, Lab Genom Func, FES,IZTACALA, Tlalnepantla, Mexico
Inst Nacl Cancerol, Lab Genom, Av San Fernando 22,Col Secc 16, Mexico City 14080, DF, Mexico
UNAM, Unidad Biomed, Lab Inmunol Parasitos, FES,IZTACALA, Tlalnepantla, Mexico
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