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FOXO3a deregulation in uterine smooth muscle tumors.
- Source :
-
Clinics (Sao Paulo, Brazil) [Clinics (Sao Paulo)] 2024 Apr 17; Vol. 79, pp. 100350. Date of Electronic Publication: 2024 Apr 17 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- Objective: The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis.<br />Methods: The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes.<br />Results: This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated.<br />Conclusions: In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.<br />Competing Interests: Declaration of competing interest The authors declare no conflict of interest and funding disclosures.<br /> (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)
- Subjects :
- Humans
Female
Middle Aged
Adult
Immunohistochemistry
Gene Expression Regulation, Neoplastic genetics
Leiomyosarcoma genetics
Leiomyosarcoma pathology
Leiomyosarcoma metabolism
Smooth Muscle Tumor genetics
Smooth Muscle Tumor pathology
Smooth Muscle Tumor metabolism
Up-Regulation
MicroRNAs genetics
MicroRNAs metabolism
Prognosis
Aged
Myometrium metabolism
Myometrium pathology
Forkhead Box Protein O3 metabolism
Forkhead Box Protein O3 genetics
Uterine Neoplasms genetics
Uterine Neoplasms pathology
Uterine Neoplasms metabolism
Leiomyoma genetics
Leiomyoma pathology
Leiomyoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1980-5322
- Volume :
- 79
- Database :
- MEDLINE
- Journal :
- Clinics (Sao Paulo, Brazil)
- Publication Type :
- Academic Journal
- Accession number :
- 38636197
- Full Text :
- https://doi.org/10.1016/j.clinsp.2024.100350