Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene
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
Affiliations
Diana Cenariu
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Alina-Andreea Zimta
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Raluca Munteanu
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Anca Onaciu
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Cristian Silviu Moldovan
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Ancuta Jurj
Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
Lajos Raduly
Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
Alin Moldovan
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Adrian Florea
Department of Cell and Molecular Biology, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania
Liviuta Budisan
Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
Laura Ancuta Pop
Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
Lorand Magdo
Faculty of Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Mihai Tudor Albu
Faculty of Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Rares Bogdan Tonea
Faculty of Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Mihai-Stefan Muresan
5th Surgical Department, Municipal Hospital, 11 Tăbăcarilor Street, 400139 Cluj-Napoca, Romania
Calin Ionescu
5th Surgical Department, Municipal Hospital, 11 Tăbăcarilor Street, 400139 Cluj-Napoca, Romania
Bogdan Petrut
Department of Urology, “Prof. Dr. Ion Chiricuta” Oncology Institute, Republicii 34–36 Street, 400015 Cluj-Napoca, Romania
Rares Buiga
Department of Pathology, “Prof. Dr. Ion Chiricuta” Oncology Institute, Republicii 34–36 Street, 400015 Cluj-Napoca, Romania
Alexandru Irimie
11th Department of Surgical Oncology and Gynaecological Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania
Diana Gulei
MEDFUTURE—Research Center for Advanced Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, Marinescu 23 Street/Louis Pasteur 4–6 Street, 400337 Cluj-Napoca, Romania
Ioana Berindan-Neagoe
Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania
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 TP53 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 TP53 in colon adenocarcinomas. Our study investigated the differential therapeutic effect of miR-125b-5p replacement in colon cancer based on the TP53 mutation status of colon cancer cell lines. In TP53 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 TP53. In TP53 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 TP53 mutated colon cancer cells, explaining partially the dual behavior of this microRNA in malignant pathologies.