A rationalized definition of general tumor suppressor microRNAs excludes miR-34a
| Autor: | Sophie Mockly, Hervé Seitz, Élisabeth Houbron |
|---|---|
| Přispěvatelé: | Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2022 |
| Předmět: |
Endogeny
Biology Transfection law.invention 03 medical and health sciences 0302 clinical medicine law [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Cell Line Tumor microRNA medicine Genetics Humans Genes Tumor Suppressor Epigenetics Gene 030304 developmental biology Cell Proliferation 0303 health sciences Cancer medicine.disease [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] 3. Good health Gene Expression Regulation Neoplastic MicroRNAs 030220 oncology & carcinogenesis Cancer research Suppressor Function (biology) |
| Zdroj: | Nucleic acids research. 50(8) |
| ISSN: | 1362-4962 |
| Popis: | While several microRNAs (miRNAs) have been proposed to act as tumor suppressors, a consensual definition of tumor suppressing miRNAs is still missing. Similarly to coding genes, we propose that tumor suppressor miRNAs must show evidence of genetic or epigenetic inactivation in cancers, and exhibit an anti-tumorigenic (e.g., anti-proliferative) activity under endogenous expression levels. Here we observe that this definition excludes the most extensively studied tumor suppressor candidate miRNA, miR-34a. In analyzable cancer types, miR-34a does not appear to be down-regulated in primary tumors relatively to normal adjacent tissues. Deletion of miR-34a is occasionally found in human cancers, but it does not seem to be driven by an anti-tumorigenic activity of the miRNA, since it is not observed upon smaller, miR-34a-specific alterations. Its anti-proliferative action was observed upon large, supra-physiological transfection of synthetic miR-34a in cultured cells, and our data indicates that endogenous miR-34a levels do not have such an effect. Our results therefore argue against a general tumor suppressive function for miR-34a, providing an explanation to the lack of efficiency of synthetic miR-34a administration against solid tumors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|