PTHrP differentially regulates miR-423 and miR-27a in normal intestinal cells and colorectal cancer cells

CARRIERE, PEDRO; CALVO NATALIA; NOVOA DÍAZ MARÍA BELEN; MORALES SONIA; MARTIN MARIA JULIA; CONTRERAS HECTOR; GENTILI CLAUDIA

Congreso; Reunión Anual de Sociedades de BioCiencias.; 2020

Sociedad Argentina de Investigación Clínica (SAIC)

MicroRNAs (miRs) are small non-coding RNAs that participate in theregulation of mRNAs at the post-transcriptional level in physiologicaland pathological processes such as cell differentiation, migration,and invasion. The differential presence of the 3p and 5p isoformsoriginating from the pre-microRNA precursor has recently beencorrelated with cancer initiation and progression. Previously, we obtainedevidence that parathyroid hormone-related peptide (PTHrP),which is overexpressed in colorectal cancer (CRC), induces molecular changes promoting angiogenesis, Epithelial-MesenchymalTransition (EMT), and cancer stem cell features in CRC cells. Theobjective of this work was to explore the potential role of PTHrPin the post-transcriptional regulation of mRNAs, evaluating the expressionof miR-423 and miR-27a isoforms in the normal intestinalCCD841 CoN cell line and in HCT116 cells derived from colorectalcancer. miR-423 is increased in the plasma of CRC patients, whilemiR-27a was identified as a tumor suppressor. Employing TaqManMicroRNA assays by qPCR, we observed that PTHrP treatmentfor 5 hours significantly increases the miR-423-3p and miR-423-5p transcripts levels in HCT116 cells; however, no changes wereevidenced in CCD841 CoN cells at the studied times. In HCT116cells, the transcription of miR-27a-5p increased at 5 hours of PTHrPexposure with a return to control levels within 24 hours. Differently,PTHrP induced a consistent decrease in miR-27a-3p transcriptionin HCT116 cells and CCD841 CoN cells at the same times. Theseresults highlight the relevance of the temporal coexistence of thetwo functional isoforms of these miRs and propose that miR-27a-3pisoform and miR-423 isoforms could be possible post-transcriptionalregulators modulated by PTHrP in intestinal tumor cells.