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Cited by 22MicroRNA in disease regulationS100 Proteins and AnnexinsCancer-related molecular mechanisms research

miR-21-5p Inhibits the Proliferation, Migration, and Invasion of Glioma by Targeting S100A10

Open access
Gao, Peng, Wang, Haopeng, Li, Huaixu, Shu, Lei, Han, Zhenyu, Li, Shiting, Cheng, Hongwei, Dai, Xingliang·2023·Journal of Cancer
DOI 10.7150/jca.84030PMC PMC10355203
Open this paper in CoChat — free accountOpen PDF

Abstract

S100A10, a member of the S100 protein family, is upregulated in multiple human malignancies and plays a key role in regulating tumor progression. This study aimed to reveal the underlying mechanism by which S100A10 in regulates the proliferation, migration, and invasion of glioma. The expression and clinical information data of S100A10 were downloaded from public databases (TCGA, CGGA, and GEPIA2). S100A10 expression levels in glioma tumor tissues and adjacent nontumor tissues were compared by immunohistochemistry (IHC). The functional roles of S100A10 in glioma were assessed by cell counting kit-8 (CCK-8) cell proliferation assay, wound healing assay, transwell assay, and flow cytometry. miRDB and double luciferase assay were used to predict and identify potential S100A10 mRNA-complementary miRNAs, and the roles of miR-21-5p in glioma cell were examined by targeted knockdown or overexpression miR-21-5p in glioma cell lines. We found that S100A10 was overexpressed in glioma tissues and predicted a worse prognosis. S100A10 knockdown significantly inhibited glioma cell proliferation, invasion, and migration. Furthermore, we demonstrated that miR-21-5p inhibits glioma proliferation, migration, and invasion by targeting S100A10. This study showed S100A10 was a new prognostic predictor among glioma patients and provided new insights into the pathogenesis of gliomas, suggesting that miR-21-5p /S100A10 axis may serve as a valuable therapeutic target for glioma.

AI snapshot

Written from the paper’s full text.

TL;DR

S100A10 is overexpressed in glioma, correlates with higher grade and worse prognosis, and its knockdown inhibits proliferation, migration, and invasion while promoting apoptosis. miR-21-5p directly targets S100A10 and suppresses glioma cell proliferation/invasion while promoting apoptosis, suggesting the miR-21-5p/S100A10 axis as a potential therapeutic target.

Key findings

  • In a TCGA cohort (n=597), S100A10 was highly expressed in glioma versus normal tissues and high S100A10 expression predicted poor overall survival; high S100A10 with wild-type PTEN, wild-type MYCN, and methylated MGMT predicted poor progression-free or overall survival, while no significant prognostic difference was seen for wild-type versus amplified EGFR.
  • In 79 primary glioma specimens (WHO II 27, III 14, IV 38), S100A10 mRNA increased with glioma grade, and immunohistochemistry showed more cytoplasmic positive cells with higher grade.
  • S100A10 knockdown in U87 and U251 cells significantly inhibited proliferation (CCK-8), invasion (Transwell), and migration (wound healing), and increased apoptosis by flow cytometry.
  • miR-21-5p was predicted and dual-luciferase-validated to bind the S100A10 3′UTR; miR-21-5p overexpression reduced S100A10 protein, inhibited proliferation, and promoted apoptosis, while miR-21-5p inhibition increased S100A10 and reduced apoptosis; si-S100A10 reversed the miR-21-5p inhibitor effects on invasion and apoptosis.

Methods

  • Public database analysis used a TCGA cohort (n=597) and GEPIA2; clinical tissue microarray, HE staining, and IHC were performed on 79 glioma patients (WHO II 27, III 14, IV 38) and six normal brain tissues from brain injury patients.
  • In vitro experiments used human glioma cell lines (U87, U251, U118, U343, SNB19, SHG44) and glial cells (NHA, G005), with qPCR, western blotting, CCK-8, wound healing, Transwell, flow cytometry, and dual-luciferase assays; siRNA knockdown, miR-21-5p mimics/inhibitor, and si-S100A10 rescue were used.
  • Statistical analysis used GraphPad Prism 8.0.2; continuous data were expressed as mean ± SD, differences were tested with Student’s t-test, and P<0.05 was considered significant.

Limitations

  • Not stated in the paper: the paper does not include an explicit limitations section.
  • Evident from the text: findings rely on in vitro cell lines and a single-institution clinical cohort (79 glioma patients; normal brain from six brain injury patients), with no in vivo animal model or independent validation cohort described.
  • Evident from the text: statistical analysis is limited to Student’s t-test with P<0.05; no effect sizes, confidence intervals, or multiple-testing correction are reported, and database analyses depend on public datasets.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.7150/jca.84030

Cites

27 of 27 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

5 of 10 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Findingown data

    S100A10 knockdown significantly reduces invasion ability of U87 and U251 glioma cells.

    “S100A10 knockdown significantly inhibited glioma cell proliferation, invasion, and migration.”
    • Also stated in: § Down-regulation of S100A10 significantly inhibited proliferation, migration, and invasion and promoted apoptosis of glioma cells · plain
      “Transwell invasion assay showed that knocking down the expression of S100A10 significantly reduced the invasion ability of U87 and U251 cell lines (Figure 3E, 3F).”
    • Also stated in: § Conclusion · plain
      “down-regulation of S100A10 expression can inhibit the proliferation, invasion, and migration of glioma cells.”
    Quote in the paperSubstantial claim
  • Findingown data

    S100A10 knockdown significantly reduces migration ability of U87 and U251 glioma cells.

    “S100A10 knockdown significantly inhibited glioma cell proliferation, invasion, and migration.”
    • Also stated in: § Down-regulation of S100A10 significantly inhibited proliferation, migration, and invasion and promoted apoptosis of glioma cells · plain
      “Cell scratch assay showed that downregulation of S100A10 significantly reduced the migration ability of U87 and U251 cell lines (Figure 3G, 3H).”
    • Also stated in: § Conclusion · plain
      “down-regulation of S100A10 expression can inhibit the proliferation, invasion, and migration of glioma cells.”
    Quote in the paperSubstantial claim
  • Findingown data

    S100A10 knockdown significantly inhibits proliferation of U87 and U251 glioma cells.

    “S100A10 knockdown significantly inhibited glioma cell proliferation, invasion, and migration.”
    • Also stated in: § Down-regulation of S100A10 significantly inhibited proliferation, migration, and invasion and promoted apoptosis of glioma cells · plain
      “CCK-8 proliferation assay showed that the downregulation of S100A10 could significantly inhibit the proliferation of U87 and U251 cell lines (Figure 3C, 3D).”
    • Also stated in: § Conclusion · plain
      “down-regulation of S100A10 expression can inhibit the proliferation, invasion, and migration of glioma cells.”
    Quote in the paperSubstantial claim
  • Findingown data

    There is no significant difference in prognosis between wild-type and amplified EGFR genes in relation to S100A10 expression in glioma.

    “while there was no significant difference in the prognosis of patients in the presence of wild-type and amplified EGFR genes (Figure 1C, 1D, 1E, 1F).”
    • Also stated in: § Discussion · plain
      “while there was no significant difference in prognosis in the presence of wild-type and amplified EGFR genes.”
    Quote in the paperNot a substantial claim
  • Findingown data

    High S100A10 expression predicts worse prognosis or overall survival in glioma patients.

    “We found that S100A10 was overexpressed in glioma tissues and predicted a worse prognosis.”
    • Also stated in: § Database analysis suggested that high expression of S100A10 in glioma tissues predicted worse prognosis · plain
      “Then we analyzed the prognosis of glioma patients with S100A10 expression in TCGA database, and found that high S100A10 expression showed a poor overall survival rate in glioma patients (Figure 1B).”
    • Also stated in: § Discussion · plain
      “The expression of S100A10 increased with the grade of glioma, but the survival rate and prognosis of glioma patients declined.”
    Quote in the paperSubstantial claim
  • May combine two claims. 11
  • Classified as probably not a substantial claim. 6
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    S100A10 is upregulated in multiple human malignancies and plays a key role in regulating tumor progression.

    “S100A10, a member of the S100 protein family, is upregulated in multiple human malignancies and plays a key role in regulating tumor progression.”
    • Also stated in: § Introduction · hedged
      “The up-regulated expression of S100A10 is involved in a variety of tumor malignant characteristics, indicating that S100A10 may be a potential tumor prognostic marker5-7.”
    • Also stated in: § Discussion · plain
      “Previous studies have found that S100A10 protein is highly expressed in malignant tumors.”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [5] Donato R S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles Int J Biochem Cell Biol 2001 33 637 68 11390274 source
    • cites [6] Kretsinger RH Nockolds CE Carp muscle calcium-binding protein II. Structure determination and general description J Biol Chem 1973 248 3313 26 4700463 source
    • cites [7] Donato R Intracellular and extracellular roles of S100 proteins Microsc Res Tech 2003 60 540 51 12645002 source

      The S100A10 section describes plasminogen activation and blood coagulation, not cancer. The Regulation of Cell Growth and Differentiation section discusses tumor-related findings for other S100 proteins, but our copy does not address whether S100A10 is upregulated in human malignancies or regulates tumor progression (searched: S100A10 with cancer, carcinoma, metastasis, and tumor). (LLM, conf=0.77)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Prognosis of glioma patients cannot be simply determined by pathological grade; molecular features such as PTEN deletion, EGFR amplification, MYCN amplification, and MGMT methylation play an important role.

    “At present, the prognosis of glioma patients cannot be simply determined by pathological grade. Molecular features such as PTEN deletion, EGFR amplification, MYCN amplification, MGMT methylation, etc. play an important role 22.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [22] Chen R Smith-Cohn M Cohen AL et al. Glioma Subclassifications and Their Clinical Significance Neurotherapeutics 2017 14 284 97 28281173 PMC5398991 source

      The Comprehensive Molecular Profiling of Infiltrative Gliomas section reports different prognoses for molecular groups even when their histologic grades overlap, and the MGMT Promoter Methylation section identifies MGMT methylation as a prognostic marker in GBM. The Therapeutics and Clinical Trial Planning section discusses EGFR amplification as a marker for treatment studies, but identifies EGFRvIII deletion—not amplification—as a negative prognostic indicator. The retrieved passages do not establish prognostic roles for PTEN deletion or MYCN amplification (pages unavailable). (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Tumor growth depends on the balance between proliferation and apoptosis.

    “Abnormal apoptosis is also an important feature of cancer cells, and tumor growth depends on the balance between proliferation and apoptosis23.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [23] Wong RS Apoptosis in cancer: from pathogenesis to treatment J Exp Clin Cancer Res 2011 30 87 21943236 PMC3197541 source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miRNAs play a key role in the progression of malignant tumors and are considered potential anti-tumor therapeutic targets.

    “miRNAs play a key role in the progression of malignant tumors, they are considered potential anti-tumor therapeutic targets24, 25.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [24] Echevarría-Vargas IM Valiyeva F Vivas-Mejía PE Upregulation of miR-21 in cisplatin resistant ovarian cancer via JNK-1/c-Jun pathway PLoS One 2014 9 e97094 24865582 PMC4035252 source
    • cites [25] Ferraro A Kontos CK Boni T et al. Epigenetic regulation of miR-21 in colorectal cancer: ITGB4 as a novel miR-21 target and a three-gene network (miR-21-ITGΒ4-PDCD4) as predictor of metastatic tumor potential Epigenetics 2014 9 129 41 24149370 PMC3928175 source

      The Introduction and the section on the three-gene assay say that miRNAs contribute to cancer pathogenesis and regulate metastatic progression. The miR-21 inhibition results also show reduced migration of colon cancer cells. However, the paper proposes a potential diagnostic tool, not miRNAs as anti-tumor therapeutic targets; that part of the claim is unsupported by our copy. Page numbers are unavailable in the indexed passages. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • The quote only partly states this claim.

    Findingown data

    S100A10 is overexpressed in glioma tissues compared with normal or adjacent nontumor tissues.

    “We found that S100A10 was overexpressed in glioma tissues and predicted a worse prognosis.”
    • Also stated in: § Database analysis suggested that high expression of S100A10 in glioma tissues predicted worse prognosis · plain
      “It was found that S100A10 showed high expression in glioma compared with normal tissues (Figure 1A).”
    • Also stated in: § Discussion · plain
      “The results showed that the expression of S100A10 in glioma tissues was higher than that in normal tissues.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: S100A10 has not been reported in gliomas.

  • May combine two claims.

    Findingown data

    miR-21-5p overexpression inhibits proliferation of U87 and U251 glioma cells, while miR-21-5p down-regulation promotes their proliferation.

    “The results showed that compared with the control group, miR-21-5p overexpression inhibited the proliferation of U87 and U251 cell lines, while miR-21-5p down-regulation promoted their proliferation (Figure 5B, 5C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    S100A10 protein expression is overexpressed by miR-21-5p inhibitor and can be reversed by adding siRNA of S100A10.

    “Western blotting assay was used to confirm the transfection effect, and the results showed that the S100A10 protein expression was overexpression by miR-21-5p inhibitor and could be reversed after adding siRNA of S100A10 (Figure 6A, 6B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-21-5p overexpression promotes apoptosis of U87 and U251 glioma cells, while inhibition of miR-21-5p reduces their apoptosis.

    “Flow cytometry was used to study the effect of miR-21-5p on apoptosis of glioma cell lines U87 and U251, and the results showed that compared with the control group, miR-21-5p overexpression promoted the apoptosis of U87 and U251 cell lines, while inhibition of miR-21-5p expression reduced the apoptosis of U87 and U251 glioma cells (Figure 5D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The 3'UTR of S100A10 contains binding sites of miR-21-5p, making miR-21-5p a potential regulatory miRNA of S100A10.

    “miRDB online database (http://mirdb.org/) was used predict regulatory miRNAs of S100A10, and the results showed that the 3'UTR of S100A10 contained binding sites of miR-21-5p, in other words, miR-21-5p is a potential regulatory miRNA of S100A10 (Figure 4A).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Each qPCR sample was assayed in triplicate.

    “A melting curve analysis of each sample was used to check the specificity of amplification, and each sample was assayed in triplicate.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The collection of samples and clinical information was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University, and written informed consent was obtained from each patient.

    “The collection of samples and clinical information in this study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University, and written informed consent was obtained from each patient.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    At least two neuropathologists diagnosed each sample in this study as diffuse glioma (WHO II, III, and IV).

    “At least two neuropathologists diagnosed each sample in this study as diffuse glioma (WHO Ⅱ, Ⅲ, and Ⅳ).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    miR-21-5p suppresses glioma cell invasion and apoptosis by targeting S100A10.

    “These results suggest that miR-21-5p suppressed glioma cell invasion and apoptosis by targeting S100A10.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    S100A10 is prevalent in the most invasive anaplastic thyroid cancer, suggesting it plays a key role in thyroid cancer progression.

    “A study find that S100A10 is a prevalent expression in the most invasive anaplastic thyroid cancer, which suggests that S100A10 plays a key role in the progression of thyroid cancer21.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Ito Y Arai K Nozawa R et al. S100A10 expression in thyroid neoplasms originating from the follicular epithelium: contribution to the aggressive characteristic of anaplastic carcinoma Anticancer Res 2007 27 2679 83 17695432

  • May combine two claims.

    Interpretationown data

    miR-21-5p targets S100A10 and negatively regulated the proliferation, invasion, and apoptosis of glioma cells.

    “miR-21-5p targets S100A10 and negatively regulated the proliferation, invasion, and apoptosis of glioma cells.”
    Quote in the paperSubstantial claim
15 of 15

  • The paper relies on this without support.

    S100A10 has not been reported in gliomas.

    “Although S100A10 has been studied in a variety of tumors, it has not been reported in gliomas.”

  • The paper relies on this without support.

    The relationship between miR-21-5p and S100A10 and how it affects glioma progression is unclear.

    “However, the relationship between miR-21-5p and S100A10 and how it affects glioma progression remains unclear.”
2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conclusion reverses miR-21-5p's reported effect on apoptosis

    Major

    The conclusion says miR-21-5p negatively regulates apoptosis, but the results say overexpressing it promotes apoptosis and inhibiting it reduces apoptosis.

  • G005 is described as both a glial and a glioma cell line

    Minor

    The cell-line methods identify G005 as glial cells, whereas the results call it a normal glioma cell line.

2 of 2

Cites

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Cited by

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Related

Authors
Gao, P., Wang, H., Li, H., Shu, L., Han, Z., Li, S., Cheng, H., & Dai, X.
Affiliations
  • Anhui Medical University (CN)
  • Shanghai Jiao Tong University (CN)
Corresponding author
  • Gao, Peng
  • Wang, Haopeng
ORCID
Venue
Journal of Cancer
Publisher
Ivyspring International Publisher
Published
2023
Volume
14
Issue
10
Pages
1781-1793
ISSN
1837-9664 (ISSN-L)
DOI
10.7150/jca.84030
PMC
PMC10355203
OpenAlex
W4383270834
Semantic Scholar
fa700774975ae047b6b7ea6fca3d94b47fbd50e7
Cited by
22
References
27
Citations by year
2026: 3 · 2025: 5 · 2024: 14
FWCI
2.23
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of Cancer (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Funders
  • Anhui Medical University (2021xkj131, 2022xkjT024)
  • Natural Science Foundation of Anhui Province (2208085MH251)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
miR-21-5p, S100A10, glioma, microRNA, tumor cell proliferation, cell migration, cell invasion, prognostic factors, therapeutic target

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