miR-200a/b/-429 downregulation is a candidate biomarker of tumor radioresistance and independent of hypoxia in locally advanced cervical cancer.
central pelvic recurrence
cervical cancer
extracellular matrix interaction
miR-200
microRNA
radioresistance
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
21
12
2021
received:
13
08
2021
accepted:
19
01
2022
pubmed:
23
1
2022
medline:
12
4
2022
entrez:
22
1
2022
Statut:
ppublish
Résumé
Many patients with locally advanced cervical cancer experience recurrence within the radiation field after chemoradiotherapy. Biomarkers of tumor radioresistance are required to identify patients in need of intensified treatment. Here, the biomarker potential of miR-200 family members was investigated in this disease. Also, involvement of tumor hypoxia in the radioresistance mechanism was determined, using a previously defined 6-gene hypoxia classifier. miR-200 expression was measured in pretreatment tumor biopsies of an explorative cohort (n = 90) and validation cohort 1 (n = 110) by RNA sequencing. Publicly available miR-200 data of 79 patients were included for the validation of prognostic significance. A score based on expression of the miR-200a/b/-429 (miR-200a, miR-200b, and miR-429) cluster showed prognostic significance in all cohorts. The score was significant in multivariate analysis of central pelvic recurrence. No association with distant recurrence or hypoxia status was found. Potential miRNA target genes were identified from gene expression profiles and showed enrichment of genes in extracellular matrix organization and cell adhesion. miR-200a/b/-429 overexpression had a pronounced radiosensitizing effect in tumor xenografts, whereas the effect was minor in vitro. In conclusion, miR-200a/b/-429 downregulation is a candidate biomarker of central pelvic recurrence and seems to predict cell adhesion-mediated tumor radioresistance independent of clinical markers and hypoxia.
Identifiants
pubmed: 35064630
doi: 10.1002/1878-0261.13184
pmc: PMC8936520
doi:
Substances chimiques
Biomarkers, Tumor
0
MIRN200 microRNA, human
0
MIRN429 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1402-1419Subventions
Organisme : Wellcome Trust
ID : 107438
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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