Hypermethylation of the Promoter Region of miR-23 Enhances the Metastasis and Proliferation of Multiple Myeloma Cells via the Aberrant Expression of uPA
Open accessAbstract
Multiple myeloma has a long course, with no obvious symptoms in the early stages. However, advanced stages are characterized by injury to the bone system and represent a severe threat to human health. The results of the present work indicate that the hypermethylation of miR-23 promoter mediates the aberrant expression of uPA/PLAU (urokinase plasminogen activator, uPA) in multiple myeloma cells. miR-23, a microRNA that potentially targets uPA’s 3’UTR, was predicted by the online tool miRDB. The endogenous expressions of uPA and miR-23 are related to disease severity in human patients, and the expression of miR-23 is negatively related to uPA expression. The hypermethylation of the promoter region of miR-23 is a promising mechanism to explain the low level of miR-23 or aberrant uPA expression associated with disease severity. Overexpression of miR-23 inhibited the expression of uPA by targeting the 3’UTR of uPA, not only in MM cell lines, but also in patient-derived cell lines. Overexpression of miR-23 also inhibited in vitro and in vivo invasion of MM cells in a nude mouse model. The results therefore extend our knowledge about uPA in MM and may assist in the development of more effective therapeutic strategies for MM treatment.
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Expression of miR-23a is reduced in osteosarcoma cells and tissues due to hypermethylation of its promoter region.
“the expression of miR-23a is reduced in osteosarcoma cells and tissues due to hypermethylation of its promoter region.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [103]
The Introduction says that miR-23 promoter hypermethylation leads to low miR-23 expression, and the Results report an inverse association in multiple myeloma specimens. The cited paper does not establish this finding in osteosarcoma cells or tissues, and the passages identify the molecule as miR-23 rather than specifically miR-23a. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredDemethylation treatment can restore miR-23a expression.
“demethylation treatment can restore miR-23a expression.”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [103]
The Results section (‘Hypermethylation of miR-23 Promoter Is Associated With Low miR-23 Levels and High uPA Levels in MM’; page unavailable) suggests that promoter hypermethylation may contribute to low miR-23 expression. It does not report that demethylation treatment restores expression, and the passages examined do not establish the claim specifically for miR-23a. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOverexpression of miR-23 can significantly inhibit uPA expression and repress the invasive ability of multiple myeloma cells under in vitro and in vivo conditions.
“overexpression of miR-23 can significantly inhibit the uPA expression and then repress the invasive ability of multiple myeloma cells under in vitro and in vivo conditions [102,103].”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [103]
The Results sections on uPA expression and in vivo invasion (page unavailable) report that miR-23 overexpression reduced uPA and inhibited MM-cell invasion in nude mice. The non-abstract passages found do not report an in vitro invasion result, so that condition is not supported by the evidence used for this verdict. (LLM, conf=0.83)
Experimental — accuracy not yet measuredEctopic expression of miR-23a significantly inhibits proliferation, migration, and invasion of osteosarcoma cells by targeting RUNX2 and CXCL12.
“Ectopic expression of miR-23a significantly inhibits the proliferation, migration, and invasion of osteosarcoma cells by targeting RUNX2 and CXCL12 in osteosarcoma”
From Recent advances of miR-23 in human diseases and growth development (2025) · cites this paper as [103]
The Discussion (page not provided) reports that overexpressing miR-23 inhibits proliferation and invasion in multiple myeloma cells by targeting uPA. It does not establish the claim about miR-23a in osteosarcoma cells, inhibition of migration, or targeting RUNX2 and CXCL12. (LLM, conf=0.86)
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- Authors
- Ran, Q., Xu, D., Wang, Q., & Wang, D.
- Affiliations
- General Hospital of Central Theater Command (CN)
- Dalian Medical University (CN)
- Corresponding author
- Ran, Qijie
- Wang, Dongsheng
- Venue
- Frontiers in Oncology
- Publisher
- Frontiers Media SA
- Published
- 2022-05-30
- Volume
- 12
- Pages
- 835299-835299
- ISSN
- 2234-943X (ISSN-L)
- PMC
- PMC9189361
- OpenAlex
- W4282021510
- Cited by
- 8
- References
- 79
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2022: 1
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Oncology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- General Hospital of People’s Liberation Army
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- multiple myeloma, miR-23, promoter hypermethylation, DNA methylation, uPA, urokinase, PLAU, metastasis, cell proliferation, tumor invasion, disease severity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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