Regulation and tumor-suppressive function of the miR-379/miR-656 (C14MC) cluster in cervical cancer.
cervical cancer
methylation
miR-379/miR-656 cluster
tumor suppressor
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
23 Feb 2024
23 Feb 2024
Historique:
revised:
05
01
2024
received:
05
09
2023
accepted:
13
02
2024
medline:
24
2
2024
pubmed:
24
2
2024
entrez:
24
2
2024
Statut:
aheadofprint
Résumé
Cervical cancer (CC) is a key contributor to cancer-related mortality in several countries. The identification of molecular markers and the underlying mechanism may help improve CC management. We studied the regulation and biological function of the chromosome 14 microRNA cluster (C14MC; miR-379/miR-656) in CC. Most C14MC members exhibited considerably lower expression in CC tissues and cell lines in The Cancer Genome Atlas (TCGA) cervical squamous cell carcinoma and endocervical adenocarcinoma patient cohorts. Bisulfite Sanger sequencing revealed hypermethylation of the C14MC promoter in CC tissues and cell lines. 5-aza-2 deoxy cytidine treatment reactivated expression of the C14MC members. We demonstrated that C14MC is a methylation-regulated miRNA cluster via artificial methylation and luciferase reporter assays. C14MC downregulation correlated with poor overall survival and may promote metastasis. C14MC activation via the lentiviral-based CRISPRa approach inhibited growth, proliferation, migration, and invasion; enhanced G2/M arrest; and induced senescence. Post-transcriptional regulatory network analysis of C14MC transcriptomic data revealed enrichment of key cancer-related pathways, such as metabolism, the cell cycle, and phosphatidylinositol 3-kinase (PI3K)-AKT signaling. Reduced cell proliferation, growth, migration, invasion, and senescence correlated with the downregulation of active AKT, MYC, and cyclin E1 (CCNE1) and the overexpression of p16, p21, and p27. We showed that C14MC miRNA activation increases reactive oxygen species (ROS) levels, intracellular Ca
Identifiants
pubmed: 38400534
doi: 10.1002/1878-0261.13611
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Science and Engineering Research Board (SERB)
ID : EMR/2016/002314
Organisme : Department of Science and Technology, Ministry of Science and Technology, India
ID : MTR/2021/000182
Organisme : Wellcome Trust DBT India Alliance, Government of India
ID : IA/I/22/1/506240
Organisme : SPARC
ID : SPARC/2019-2020/P2297/SL
Organisme : Manipal Academy of Higher Education, Manipal
Organisme : Technology Information Forecasting and Assessment Council (TIFAC) Core in Pharmacogenomics at MAHE, the Manipal
Organisme : Fund for Improvement of S&T Infrastructure (FIST), Department of Science and Technology, Government of India
Organisme : Karnataka Fund for Infrastructure Strengthening in Science and Technology (K-FIST), the Government of Karnataka
Organisme : Builder Grant, Department of Biotechnology, Government of India
Informations de copyright
© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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