Inhibition of Wnt-beta-Catenin Signaling by ICRT14 Drug Depends of Post-Transcriptional Regulation by HOTAIR in Human Cervical Cancer HeLa Cells
Por:
Trujano-Camacho, Samuel, Cantu-de Leon, David, Delgado-Waldo, Izamary, Coronel-Hernandez, Jossimar, Millan-Catalan, Oliver, Hernandez-Sotelo, Daniel, Lopez-Camarillo, Cesar, Perez-Plasencia, Carlos, Campos-Parra, Alma D.
Publicada:
28 oct 2021
Resumen:
Background: In Cervical cancer (CC), in addition to HPV infection, the
most relevant alteration during CC initiation and progression is the
aberrant activation of Wnt/beta-catenin pathway. Several inhibitory
drugs of this pathway are undergoing preclinical and clinical studies.
Long non-coding RNAs (lncRNAs) are associated with resistance to
treatments. In this regard, understanding the efficiency of drugs that
block the Wnt/beta-catenin pathway in CC is of relevance to eventually
propose successful target therapies in patients with this disease.
Methods: We analyzed the levels of expression of 249 components of the
Wnt/beta-catenin pathway in a group of 109 CC patients. Three drugs that
blocking specific elements of Wnt/beta-catenin pathway (C59, NSC668036
and ICRT14) by TOP FLASH assays and qRT-PCR were tested in vitro in CC
cells.
Results: 137 genes of the Wnt/beta-catenin pathway were up-regulated and
112 down-regulated in CC patient's samples, demonstrating that this
pathway is dysregulated. C59 was an efficient drug to inhibit
Wnt/beta-catenin pathway in CC cells. NSC668036, was not able to inhibit
the transcriptional activity of the Wnt/beta-catenin pathway.
Strikingly, ICRT14 was neither able to inhibit this pathway in HeLa
cells, due to HOTAIR interaction with beta-catenin, maintaining the
Wnt/beta-catenin pathway activated.
Conclusions: These results demonstrate a mechanism by which HOTAIR
evades the effect of ICRT14, a Wnt/beta-catenin pathway inhibitory drug,
in HeLa cell line. The emergence of these mechanisms reveals new
scenarios in the design of target therapies used in cancer.
Filiaciones:
Trujano-Camacho, Samuel:
Postgraduate in Experimental Biology, DCBS, Autonomous Metropolitan University-Iztapalapa, Iztapalapa, Mexico
Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Cantu-de Leon, David:
Unidad de Investigaciones Biomédicas en Cancerología, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Delgado-Waldo, Izamary:
Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Coronel-Hernandez, Jossimar:
Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Millan-Catalan, Oliver:
Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Hernandez-Sotelo, Daniel:
Laboratorio de Epigenética del Cáncer, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo de los Bravo, Mexico
Lopez-Camarillo, Cesar:
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Ciudad de Mexico, Mexico
Perez-Plasencia, Carlos:
Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, Mexico
Campos-Parra, Alma D.:
Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), Ciudad de México, Mexico
Green Published, gold, All Open Access; Gold
|