Hsa-miR-125b Therapeutic Role in Colon Cancer Is Dependent on the Mutation Status of the TP53 Gene.
Diana CenariuAlina-Andreea ZimtaRaluca Andrada MunteanuAnca OnaciuCristian Silviu MoldovanAncuta JurjLajos RadulyAlin Iulian MoldovanAdrian FloreaLiviuta BudisanLaura-Ancuta PopLorand MagdoMihai Tudor AlbuRares Bogdan ToneaMihai-Stefan MuresanCalin IonescuBogdan PetrutRares BuigaAlexandru IrimieDiana GuleiIoana Berindan NeagoePublished in: Pharmaceutics (2021)
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.
Keyphrases
- wild type
- papillary thyroid
- end stage renal disease
- cell proliferation
- squamous cell
- ejection fraction
- genome wide
- copy number
- squamous cell carcinoma
- chronic kidney disease
- transcription factor
- newly diagnosed
- single molecule
- bone marrow
- patient reported outcomes
- young adults
- high resolution
- cell cycle arrest
- cell death
- lymph node metastasis
- childhood cancer
- circulating tumor