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miR‑27a‑3p upregulation by p65 facilitates cervical tumorigenesis by increasing TAB3 expression and is involved in the positive feedback loop of NF‑κB signaling.
- Source :
-
Oncology reports [Oncol Rep] 2023 Jul; Vol. 50 (1). Date of Electronic Publication: 2023 May 19. - Publication Year :
- 2023
-
Abstract
- An altered microRNA (miRNA/miR)‑27a‑3p expression has been identified in cervical cancer, while the exact regulatory mechanisms responsible for the dysregulation of miR‑27a‑3p remain to be fully elucidated. In the present study, a NF‑κB/p65 binding site was identified upstream of the miR‑23a/27a/24‑2 cluster and p65 binding enhanced the transcription of pri‑miR‑23a/27a/24‑2, as well as the expression levels of mature miRNAs, including miR‑27a‑3p in HeLa cells. Mechanistically, using bioinformatics analyses and experimental validation, TGF‑β activated kinase 1 binding protein 3 (TAB3) was identified as a direct target of miR‑27a‑3p. By binding to the 3'UTR of TAB3, miR‑27a‑3p significantly enhanced TAB3 expression. Functionally, it was found that the overexpression of miR‑27a‑3p and TAB3 promoted the malignant potential of cervical cancer cells, as evaluated using cell growth, migration and invasion assays, and specific cell marker determinations in the epithelial mesenchymal transition progression, and vice versa. Further rescue experiments revealed that the enhanced malignant effects induced by miR‑27a‑3p were mediated via its upregulation of TAB3 expression. Moreover, miR‑27a‑3p and TAB3 also activated the NF‑κB signaling pathway and formed a positive feedback regulatory loop composing of p65/miR‑27a‑3p/TAB3/NF‑κB. On the whole, the findings presented herein may provide novel insight into the underlying cervical tumorigenesis and novel biomarker identification for clinical applications.
- Subjects :
- Transcription Factor RelA metabolism
NF-kappa B metabolism
Feedback, Physiological
Uterine Cervical Neoplasms genetics
Uterine Cervical Neoplasms physiopathology
HeLa Cells
Cell Line, Tumor
Protein Binding
Humans
Up-Regulation
Carcinogenesis genetics
MicroRNAs genetics
MicroRNAs metabolism
Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 50
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 37203408
- Full Text :
- https://doi.org/10.3892/or.2023.8569