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

Pharmaceutics

Alexandru Irimie¹  Calin Ionescu²  Mihai-Stefan Muresan²  Adrian Florea³  Rares Buiga⁴  Bogdan Petrut⁵  RaresBogdan Tonea⁶  Lorand Magdo⁶  MihaiTudor Albu⁶  CristianSilviu Moldovan⁷  Alina-Andreea Zimta⁷  Raluca Munteanu⁷  Alin Moldovan⁷  Diana Gulei⁷  Anca Onaciu⁷  Diana Cenariu⁷  Lajos Raduly⁸  Ancuta Jurj⁸  LauraAncuta Pop⁸  Liviuta Budisan⁸  Ioana Berindan-Neagoe⁸ 

[1] 11th Department of Surgical Oncology and Gynaecological Oncology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania;5th Surgical Department, Municipal Hospital, 11 Tăbăcarilor Street, 400139 Cluj-Napoca, Romania;Department of Cell and Molecular Biology, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, 6 Louis Pasteur St., 400349 Cluj-Napoca, Romania;Department of Pathology, “Prof. Dr. Ion Chiricuta” Oncology Institute, Republicii 34–36 Street, 400015 Cluj-Napoca, Romania;Department of Urology, “Prof. Dr. Ion Chiricuta” Oncology Institute, Republicii 34–36 Street, 400015 Cluj-Napoca, Romania;Faculty of Medicine, “Iuliu-Hatieganu” University of Medicine and Pharmacy, 8 Victor Babes Street, 400012 Cluj-Napoca, Romania;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;Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337 Cluj-Napoca, Romania;

关键词: colon cancer;    colorectal cancer;    miR-125b;    therapy;    TP53;    mutation;   

DOI  :  10.3390/pharmaceutics13050664

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown