| Title: |
LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation |
| Authors: |
Asad Ali, Katia Grillone, Serena Ascrizzi, Giulio Caridà, Lucia Fiorillo, Domenico Ciliberto, Nicoletta Staropoli, Pierosandro Tagliaferri, Pierfrancesco Tassone, Maria Teresa Di Martino |
| Source: |
Molecular Therapy: Nucleic Acids, Vol 35, Iss 2, Pp 102221- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Therapeutics. Pharmacology |
| Subject Terms: |
MT: Oligonucleotides: Therapies and Applications, microRNAs, miRNA, miRNA inhibition, miR-221, LNA-i-miR-221, Therapeutics. Pharmacology, RM1-950 |
| More Details: |
Colorectal cancer (CRC) is one of the most common malignancies and a relevant cause of cancer-related deaths worldwide. Dysregulation of microRNA (miRNA) expression has been associated with the development and progression of various cancers, including CRC. Among them, miR-221 emerged as an oncogenic driver, whose high expression is associated with poor patient prognosis. The present study was conceived to investigate the anti-CRC activity of miR-221 silencing based on early clinical data achieved from a first-in-human study by our group. Going back from bedside to bench, we demonstrated that LNA-i-miR-221 reduces cell viability, induces apoptosis in vitro, and impairs tumor growth in preclinical in vivo models of CRC. Importantly, we disclosed that miR-221 directly targets TP53BP2, which, together with TP53INP1, is known as a positive regulator of the TP53 apoptotic pathway. We found that (1) both these genes are overexpressed following miR-221 inhibition, (2) the strong anti-tumor activity of LNA-i-miR-221 was selectively observed on TP53 wild-type cells, and (3) this activity was reduced in the presence of the TP53-inhibitor Pifitrin-α. Our data pave the way to further investigations on TP53 functionality as a marker predictive of response to miR-221 silencing, which might be relevant for clinical applications. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2162-2531 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S2162253124001082; https://doaj.org/toc/2162-2531 |
| DOI: |
10.1016/j.omtn.2024.102221 |
| Access URL: |
https://doaj.org/article/3da076c66b4d4799a8feb9a8d50480d2 |
| Accession Number: |
edsdoj.3da076c66b4d4799a8feb9a8d50480d2 |
| Database: |
Directory of Open Access Journals |
