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Cited by 89MicroRNA in disease regulationCancer-related molecular mechanisms researchEndometrial and Cervical Cancer Treatments

MicroRNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-α

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Chen, Shuo, Sun, Kai-Xuan, Liu, Bo-Liang, Zong, Zhi-Hong, Zhao, Yang·2016·Molecular Cancer
DOI 10.1186/s12943-016-0496-4PMC PMC4736705
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Abstract

BACKGROUND: Endometrial carcinoma (EC) is one of the most lethal gynecologic cancers. Patients frequently have regional or distant metastasis at diagnosis. MicroRNAs are small non-coding RNAs that participate in numerous biological processes. Recent studies have demonstrated that miR-505 is associated with several types of cancer; however, the expression and function of miR-505 have not been investigated in EC. METHODS: miR-505 expression in normal endometrial tissue, endometrial carcinomas were quantified by Quantitative reverse transcription PCR. The endometrial carcinoma cell lines HEC-1B and Ishikawa were each transfected with miR-505 or scrambled mimics, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-505 and its target gene TGF-α. RESULTS: RT-PCR results demonstrated that miR-505 was significantly downregulated in human EC tissues compared to normal endometrial tissues. Besides, miR-505 expression was negatively associated with FIGO stage (stage I-II vs. III-IV), and lymph node metastasis (negative vs. positive). In vitro, overexpression of miR-505 significantly suppressed EC cell proliferation, increased apoptosis and reduced migratory and invasive activity. A miR-505 binding site was identified in the 3' untranslated region of TGF-α mRNA (TGFA) using miRNA target-detecting software; a dual luciferase reporter assay confirmed that miR-505 directly targets and regulates TGFA. RT-PCR and Western-blotting results indicated that overexpressing miR-505 reduced the expression of TGF-α and the TGF-α-regulated proteins MMP2, MMP9, CDK2, while induced Bax and cleaved-PARP expression in EC cells. In vivo, overexpression of miR-505 reduced the tumorigenicity and inhibited the growth of xenograft tumors in a mouse model of EC. CONCLUSIONS: Taken together, this study demonstrates that miR-505 acts as tumor suppressor in EC by regulating TGF-α.

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  • miR-505-3p is known to have a tumor suppressor role.

    “miR-505-3p is one of the miR types known to have a tumor suppressor role (14)(15)(16)(17).”

    From Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression (2026) · cites this paper as [14]

    The Abstract Conclusions (page unavailable) state that miR-505 acts as a tumor suppressor in endometrial cancer, supported by the reported cell and mouse experiments. Our copy calls it miR-505, not miR-505-3p, so it does not establish the claim’s strand-specific designation. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Chen, S., Sun, K.-X., Liu, B.-L., Zong, Z.-H., & Zhao, Y.
Affiliations
  • First Hospital of China Medical University (CN)
  • China Medical University (CN)
Corresponding author
Zhao, Yang
ORCID
Venue
Molecular Cancer
Publisher
Springer Science and Business Media LLC
Published
2016-02-02
Volume
15
Issue
1
Pages
11-11
ISSN
1476-4598 (ISSN-L)
DOI
10.1186/s12943-016-0496-4
PMC
PMC4736705
OpenAlex
W2271267346
Cited by
89
References
2
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 11 · 2019: 15 · 2018: 16 · 2017: 12 · 2016: 8
FWCI
7.08
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Natural Scientific Foundation of China (81202049)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
Keywords
miR-505, microRNA, endometrial cancer, tumor suppressor, transforming growth factor-alpha, 3' untranslated region, cell proliferation, apoptosis, cell migration and invasion, lymph node metastasis, tumor xenografts, MMP-2, MMP-9, CDK2, Bax, cleaved PARP
MeSH terms
Animals, Base Sequence, Disease Models, Animal, Female, Humans, Mice, Inbred BALB C, Molecular Sequence Data, Neoplasm Invasiveness, Neoplasm Metastasis, Transfection, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Transforming Growth Factor alpha, Endometrial Neoplasms, Apoptosis, Xenograft Model Antitumor Assays, MicroRNAs, Cell Line, Tumor, Cell Proliferation, G1 Phase Cell Cycle Checkpoints, Carcinogenesis

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