Deregulation of the miR-19b/PPP2R5E Signaling Axis Shows High Functional Impact in Colorectal Cancer Cells
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Published:2023-04-24
Issue:9
Volume:24
Page:7779
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Santos Andrea12ORCID, Cristóbal Ion12ORCID, Caramés Cristina13ORCID, Luque Melani4, Sanz-Álvarez Marta4, Madoz-Gúrpide Juan4ORCID, Rojo Federico4, García-Foncillas Jesús23
Affiliation:
1. Cancer Unit for Research on Novel Therapeutic Targets, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, 28040 Madrid, Spain 2. Translational Oncology Division, Oncohealth Institute, IIS-Fundación Jiménez Díaz-UAM, 28040 Madrid, Spain 3. Medical Oncology Department, University Hospital “Fundación Jiménez Díaz”, UAM, 28040 Madrid, Spain 4. Pathology Department, IIS-Fundación Jiménez Díaz-UAM, 28040 Madrid, Spain
Abstract
MicroRNA (miR)-19b is deregulated in colorectal cancer (CRC) and locally advanced rectal cancer (LARC), predicting worse outcome and disease progression in CRC patients, and acting as a promising prognostic marker of patient recurrence and pathological response to 5-fluorouracil (5-FU)-based neoadjuvant chemoradiotherapy in LARC. Moreover, there is a strong inverse correlation between miR-19b and PPP2R5E in LARC, and both predict the response to neoadjuvant therapy in LARC patients. However, the functional role of the miR-19b/PPP2R5E axis in CRC cells remains to be experimentally evaluated. Here, we confirm with luciferase assays that miR-19b is a direct negative regulator of PPP2R5E in CRC, which is concordant with the observed decreased PP2A activity levels after miR-19b overexpression. Furthermore, PPP2R5E downregulation plays a key role mediating miR-19b-induced oncogenic effects, increasing cell viability, colonosphere formation ability, and the migration of CRC cells. Lastly, we also confirm the role of miR-19b mediating 5-FU sensitivity of CRC cells through negative PPP2R5E regulation. Altogether, our findings demonstrate the functional relevance of the miR-19b/PPP2R5E signaling pathway in disease progression, and its potential therapeutic value determining the 5-FU response of CRC cells.
Funder
Instituto de Salud Carlos III, RETICS Red de Biobancos
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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