Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene

• Main Authors: Diana Cenariu, Alina-Andreea Zimta, Raluca Munteanu, Anca Onaciu, Cristian Silviu Moldovan, Ancuta Jurj, Lajos Raduly, Alin Moldovan, Adrian Florea, Liviuta Budisan, Laura Ancuta Pop, Lorand Magdo, Mihai Tudor Albu, Rares Bogdan Tonea, Mihai-Stefan Muresan, Calin Ionescu, Bogdan Petrut, Rares Buiga, Alexandru Irimie, Diana Gulei, Ioana Berindan-Neagoe
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Pharmaceutics
• Subjects: colon cancer; colorectal cancer; miR-125b; therapy; <i>TP53</i>; mutation
• Online Access: https://www.mdpi.com/1999-4923/13/5/664

Colon cancer is the third most common cancer type worldwide and is highly dependent on DNA mutations that progressively appear and accumulate in the normal colon epithelium. Mutations in the <i>TP53</i> gene appear in approximately half of these patients and have significant implications in disease progression and response to therapy. miR-125b-5p is a controversial microRNA with a dual role in cancer that has been reported to target specifically <i>TP53</i> in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the <i>TP53</i> mutation status of colon cancer cell lines. In <i>TP53</i> mutated models, miR-125b-5p overexpression slows cancer cells’ malignant behavior by inhibiting the invasion/migration and colony formation capacity via direct downregulation of mutated <i>TP53</i>. In <i>TP53</i> wild type cells, the exogenous modulation of miR-125b-5p did not significantly affect the molecular and phenotypic profile. In conclusion, our data show that miR-125b-5p has an anti-cancer effect only in <i>TP53</i> mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies.