Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
September-2026 Volume 69 Issue 3

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2026 Volume 69 Issue 3

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data1.pdf
    • Supplementary_Data2.pdf
Article Open Access

T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription

  • Authors:
    • Hongsai Hu
    • Rong He
    • Minji Liu
    • Xuli Liu
    • Qiongjia Ai
    • Min Chen
    • Qian Wang
    • Wenhui Chen
    • Weiming Qu
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan 412007, P.R. China, Zhuzhou Clinical College, Jishou University, Jishou, Hunan 416000, P.R. China
    Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 100
    |
    Published online on: July 9, 2026
       https://doi.org/10.3892/ijo.2026.5913
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

The present study aimed to investigate the involvement of T‑box transcription factor 15 (TBX15) in the immune evasion by gastric cancer (GC) cells, as well as the molecular pathways that regulate TBX15 upstream and downstream. GC and paracancerous tissues were collected to verify the expression of TBX15, matrix metalloproteinase 14 (MMP14) and methyltransferase‑like 3 (METTL3) using reverse transcription‑quantitative PCR and western blotting. The co‑culture system of GC cell‑tumor‑associated macrophages (TAMs) and mouse forestomach carcinoma (MFC) cell‑CD8+ T cells was constructed. TBX15, MMP14 and METTL3 were highly expressed in GC tissues. Kaplan‑Meier analyses were performed, and high TBX15 expression predicted a poor prognosis for patients with GC. Silencing TBX15 promoted GC cell apoptosis and inhibited tumor development and the activity of proliferation, migration and invasion. TBX15 targeted the MMP14 promoter by using ChIP‑qPCR. Overexpression of MMP14 attenuated the reduction caused by TBX15 silencing. METTL3 targets TBX15 mRNA and regulates the m6A level of TBX15. TBX15 is associated with macrophage and CD8+ T cell infiltration. In the co‑culture system of GC‑TAM and MFC‑CD8+ T cells, TBX15 overexpression alleviated the decrease in M2 polarization and activation of CD8+ T cell antitumor activity caused by METTL3 silencing. However, MMP14 overexpression resulted in TBX15 silence‑induced decreases in M1 macrophage polarization and CD8+ T cell activity. These data suggested that TBX15, correlated with poor prognosis in patients with GC, promotes immune escape in GC cells. TBX15, regulated by m6A methylation, targeted the MMP14 promoter, thereby regulating MMP14 expression. The METTL3/TBX15/MMP14 signaling axis was involved in GC cell development, M2 macrophage polarization and CD8+ T cell antitumor activity activation. These findings provide a fundamental experimental rationale for TBX15 as a potential therapeutic target for GC.
View Figures

Figure 1

TBX15 is associated with poor
prognosis of patients with GC. (A) TBX15 expression in The
Cancer Genome Atlas-STAD data (unpaired and paired samples).
****P<0.0001. (B) Survival analysis of patients with
GC with high and low TBX15. (C-E) TBX15 levels. Scale bars,
100 and 25 µm. ***P<0.001 vs. paracancerous,
two-tailed t-test. TBX15, T-box transcription factor 15; STAD,
stomach adenocarcinoma; GC, gastric cancer.

Figure 2

Silencing TBX15 inhibits the
proliferation, migration and invasion of HGC27 cells. (A) In GES-1
and GC cells (HGC27 and MKN74), TBX15 expression was verified.
**P<0.01 and ***P<0.001 vs. GES-1,
one-way ANOVA. (B) TBX15 mRNA and protein levels were
detected after silencing TBX15 in HGC27. (C) Cell Counting
Kit-8 assay. (D) EdU analysis. Scale bar, 50 µm. (E) Flow
cytometric analysis of GC cell apoptosis levels. (F) Wound healing
analysis. Scale bar, 100 µm. (G) Transwell assay was used to
analyze cell invasion ability. Scale bar, 100 µm.
***P<0.001 vs. si-NC, one-way ANOVA and two-way
ANOVA. TBX15, T-box transcription factor 15; GC, gastric cancer;
si-, small interfering; NC, negative control.

Figure 3

TBX15 silencing inhibits GC
development. (A) Tumor growth curve. (B) View of the tumor. (C)
Tumor weight. (D) Expression of TBX15. (E) TUNEL staining analysis.
Scale bar, 25 µm. (F) Immunohistochemistry was used to
analyze Ki67 expression. Scale bars, 100 and 25 µm.
**P<0.01 and ***P<0.001 vs. sh-NC,
one-way ANOVA and two-way ANOVA. TBX15, T-box transcription factor
15; sh-, short hairpin; NC, negative control; GC, gastric
cancer.

Figure 4

Transcription factor TBX15 targeted
the MMP14 promoter. (A) Correlation analysis between
TBX15 and MMP14 (n=375). (B) MMP14 expression.
***P<0.001 vs. paracancerous, two-tailed t-test. (C)
Pearson correlation analysis. (D) Binding sites between
transcription factor TBX15 and MMP14 promoter and the matrix
for TBX15 binding. (E) The MMP14 promoter activity was
validated. (F) ChIP-PCR analysis. (G) Levels of TBX15 and
MMP14 mRNA. (H) Protein expression of TBX15 and MMP14.
***P<0.001 vs. oe-NC, two-way ANOVA. TBX15, T-box
transcription factor 15; MMP14, matrix metalloproteinase 14; oe-,
overexpression; NC, negative control.

Figure 5

TBX15 and MMP14 participate in
macrophage polarization and CD8+ T cell processes. (A)
TBX15 and MMP14 mRNA levels in HGC27 cells. (B and C)
Percentage of M1- and M2-type macrophages in the co-culture system
of GC cell-TAMs. (D and E) Expression of iNOS, IL-1β,
TNF-α, Arg-1, IL-10 and CD206.
*P<0.05 and ***P<0.001 vs. M0;
#P<0.05 and ###P<0.001 vs. si-NC/TAM;
&P<0.05, &&P<0.01 and
&&&P<0.001 vs. (si-TBX15 +
oe-NC)/TAM, one-way ANOVA and two-way ANOVA. (F) TBX15 and
MMP14 mRNA levels in MFC. (G) Expression of GZMB, PFP,
CD100, IFN-γ and TNF-α in the co-culture system of MFC
cell-CD8+ T cells. ***P<0.001 vs. control;
###P<0.001 vs. si-NC/CD8+ T;
&P<0.05 and &&&P<0.001
vs. (si-TBX15 + oe-NC)/CD8+ T, two-way ANOVA.
TBX15, T-box transcription factor 15; MMP14, matrix
metalloproteinase 14; TAMs, tumor-associated macrophages; iNOS,
inducible nitric oxide synthase; oe-, overexpression; NC, negative
control; si-, small interfering; MFC, mouse forestomach carcinoma;
GZMB, granzyme B; PFP, perforin.

Figure 6

Silencing METTL3 inhibits the
m6A level of TBX15. (A and B) Levels of METTL3 in GC
tissues. (C) Total m6A methylation level. **P<0.01
and ***P<0.001 vs. paracancerous, two-tailed t-test.
(D and E) Expression of METTL3 in HGC27. (F) Total m6A methylation
level. **P<0.01 and ***P<0.001 vs.
GSE-1, one-way ANOVA. (G) METTL3 levels were detected after
silencing METTL3 in HGC27. (H) The m6A level of
TBX15. (I) RNA Pull-down assay. (J) The stability of
TBX15 mRNA. *P<0.05 and
***P<0.001 vs. si-NC, one-way ANOVA and two-way
ANOVA. METTL3, methyltransferase-like 3; m6A, N6-methyladenosine;
TBX15, T-box transcription factor 15; NC, negative control; si-,
small interfering; GC, gastric cancer.

Figure 7

METTL3 regulates GC cell function and
development through the TBX15/MMP14 signaling axis. (A) The
expression of METTL3, TBX15 and MMP14 was identified after
METTL3 silencing and TBX15 overexpression. (B and C)
Analysis of GC cell proliferation activity. Scale bar, 50
µm. (D) Flow cytometric analysis of GC cell apoptosis. (E
and F) Migration and invasion assays. Scale bar, 100 µm.
***P<0.001 vs. si-NC; ##P<0.01 and
###P<0.001 vs. si-METTL3 + oe-NC, one-way
ANOVA and two-way ANOVA. (G and H) In the co-culture system of GC
cell-macrophages, the proportion of M1 and M2 macrophages was
analyzed after METTL3 silencing and TBX15
overexpression intervention. (I and J) Levels of iNOS,
IL-1β, TNF-α, Arg-1, IL-10 and
CD206. &P<0.05,
&&P<0.01 and
&&&P<0.001 vs. M0; *P<0.05,
**P<0.01 and ***P<0.001 vs si-NC/TAM;
#P<0.05 and ###P<0.001 vs.
(si-METTL3 + oe-NC)/TAM, one-way ANOVA and two-way ANOVA.
(K) Levels of CD8+ T cell-related cytokines (GZMB, PFP,
CD100, IFN-γ and TNF-α) expression after intervention of
METTL3 silencing and TBX15 overexpression.
&&&P<0.001 vs. control,
***P<0.001 vs. si-NC/CD8+ T and
###P<0.001 vs. (si-METTL3 +
oe-NC)/CD8+ T, two-way ANOVA. METTL3,
methyltransferase-like 3; GC, gastric cancer; TBX15, T-box
transcription factor 15; MMP14, matrix metalloproteinase 14; NC,
negative control; si-, small interfering; oe-, overexpression;
GZMB, granzyme B; PFP, perforin.

Figure 8

In vivo experimental
validation of the METTL3/TBX15/MMP14 axis. (A) Tumor growth curve.
(B) Images of the tumor. (C) Tumor weight. (D and E) METTL3, TBX15
and MMP14 levels in tumors. (F) TUNEL analysis. Scale bar, 25
µm. (G) Ki67 expression via immunohistochemical analysis.
Scale bar, 25 µm. (H) Levels of iNOS, IL-1β, TNF-α, Arg-1,
IL-10 and CD206. (I) PD-L1, CD100, IFN-γ and TNF-α expression via
immunohistochemical analysis. *P<0.05 and
***P<0.001 vs. sh-NC; #P<0.05,
##P<0.01 and ###P<0.001 vs.
sh-METTL3 + oe-NC, one-way ANOVA and two-way ANOVA. METTL3,
methyltransferase-like 3; TBX15, T-box transcription factor 15;
MMP14, matrix metalloproteinase 14; iNOS, inducible nitric oxide
synthase; PD-L1, programmed death-ligand 1; IFN, interferon; NC,
negative control; oe-, overexpression; sh-, short hairpin.
View References

1 

Qiu H, Cao S and Xu R: Cancer incidence, mortality, and burden in China: A time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020. Cancer Commun (Lond). 41:1037–1048. 2021. View Article : Google Scholar : PubMed/NCBI

2 

Tan P and Yeoh KG: Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology. 149:1153–1162.e3. 2015. View Article : Google Scholar

3 

Zhang M, Zhong A, Liu H, Zhao L, Wang Y, Lu Z, Zhang L, Pan X, Liang Z, Gao L, et al: EZH2 loss promotes gastric squamous cell carcinoma. Nat Commun. 16:60322025. View Article : Google Scholar : PubMed/NCBI

4 

Tao B, Wang Z, Wang X, Song A, Liu J, Wang J, Zhang Q, Chen Z, Wang Z, Xu W, et al: An inherited predisposition allele promotes gastric cancer via enhancing deubiquitination-mediated activation of epithelial-to-mesenchymal transition signaling. J Clin Invest. 135:e1796172025. View Article : Google Scholar : PubMed/NCBI

5 

Cancer Genome Atlas Research Network: Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 513:202–209. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Keller G, Grimm V, Vogelsang H, Bischoff P, Mueller J, Siewert JR and Höfler H: Analysis for microsatellite instability and mutations of the DNA mismatch repair gene hMLH1 in familial gastric cancer. Int J Cancer. 68:571–576. 1996. View Article : Google Scholar : PubMed/NCBI

7 

Richards FM, McKee SA, Rajpar MH, Cole TR, Evans DG, Jankowski JA, McKeown C, Sanders DS and Maher ER: Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer. Hum Mol Genet. 8:607–610. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Lu L, Mullins CS, Schafmayer C, Zeißig S and Linnebacher M: A global assessment of recent trends in gastrointestinal cancer and lifestyle-associated risk factors. Cancer Commun (Lond). 41:1137–1151. 2021. View Article : Google Scholar : PubMed/NCBI

9 

Ajani JA, Lee J, Sano T, Janjigian YY, Fan D and Song S: Gastric adenocarcinoma. Nat Rev Dis Primers. 3:170362017. View Article : Google Scholar : PubMed/NCBI

10 

Matsuoka T and Yashiro M: Bioinformatics analysis and validation of potential markers associated with prediction and prognosis of gastric cancer. Int J Mol Sci. 25:58802024. View Article : Google Scholar : PubMed/NCBI

11 

Guan WL, He Y and Xu RH: Gastric cancer treatment: Recent progress and future perspectives. J Hematol Oncol. 16:572023. View Article : Google Scholar : PubMed/NCBI

12 

Farin HF, Bussen M, Schmidt MK, Singh MK, Schuster-Gossler K and Kispert A: Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J Biol Chem. 282:25748–25759. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Kispert A and Herrmann BG: The Brachyury gene encodes a novel DNA binding protein. Embo J. 12:3211–3220. 1993. View Article : Google Scholar : PubMed/NCBI

14 

Ahmed A, Syed JN, Chi L, Wang Y, Perez-Romero C, Lee D, Kocaqi E, Caballero A, Yang J, Escalante-Covarrubias Q, et al: KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy. Nat Cardiovasc Res. 2:174–191. 2023. View Article : Google Scholar : PubMed/NCBI

15 

Ye W, Wang Y, Hou S, Mei B, Liu X, Huang H, Zhou Q, Niu Y, Chen Y, Zhang M and Huang Q: USF3 modulates osteoporosis risk by targeting WNT16, RANKL, RUNX2, and two GWAS lead SNPs rs2908007 and rs4531631. Hum Mutat. 42:37–49. 2021. View Article : Google Scholar

16 

Pan DZ, Miao Z, Comenho C, Rajkumar S, Koka A, Lee SHT, Alvarez M, Kaminska D, Ko A, Sinsheimer JS, et al: Identification of TBX15 as an adipose master trans regulator of abdominal obesity genes. Genome Med. 13:1232021. View Article : Google Scholar : PubMed/NCBI

17 

Li P, Li Y, Bai S, Zhang Y and Zhao L: miR-4732-3p prevents lung cancer progression via inhibition of the TBX15/TNFSF11 axis. Epigenomics. 15:195–207. 2023. View Article : Google Scholar : PubMed/NCBI

18 

Ge Y, Jia B, Zhang P, Chen B, Liu L, Shi Y, Huang S, Liu X, Wang R, Xie Y, et al: TBX15 facilitates malignant progression of glioma by transcriptional activation of TXDNC5. iScience. 27:1089502024. View Article : Google Scholar : PubMed/NCBI

19 

Yan D, Yu Y, Ni Q, Meng Q, Wu H, Ding S, Liu X, Tang C, Liu Q and Yang K: The overexpression and clinical significance of TBX15 in human gliomas. Sci Rep. 13:97712023. View Article : Google Scholar : PubMed/NCBI

20 

Golozar M, Motlagh AV, Mahdevar M, Peymani M, InanlooRahatloo K and Ghaedi K: TBX15 and SDHB expression changes in colorectal cancer serve as potential prognostic biomarkers. Exp Mol Pathol. 136:1048902024. View Article : Google Scholar : PubMed/NCBI

21 

Gu P and Wu LN: Sulforaphane targets the TBX15/KIF2C pathway to repress glycolysis and cell proliferation in gastric carcinoma cells. Nutr Cancer. 75:1263–1270. 2023. View Article : Google Scholar : PubMed/NCBI

22 

Wei G: RNA m6A modification, signals for degradation or stabilisation? Biochem Soc Trans. 52:707–717. 2024. View Article : Google Scholar : PubMed/NCBI

23 

Hu Y, Gong C, Li Z, Liu J, Chen Y, Huang Y, Luo Q, Wang S, Hou Y, Yang S and Xiao Y: Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification. Mol Cancer. 21:342022. View Article : Google Scholar : PubMed/NCBI

24 

Shu F, Liu H, Chen X, Liu Y, Zhou J, Tang L, Cao W, Yang S, Long Y, Li R, et al: m6A modification promotes EMT and metastasis of castration-resistant prostate cancer by upregulating NFIB. Cancer Res. 84:1947–1962. 2024. View Article : Google Scholar : PubMed/NCBI

25 

Wang J, Zhang J, Liu H, Meng L, Gao X, Zhao Y, Wang C, Gao X, Fan A, Cao T, et al: N6-methyladenosine reader hnRNPA2B1 recognizes and stabilizes NEAT1 to confer chemoresistance in gastric cancer. Cancer Commun (Lond). 44:469–490. 2024. View Article : Google Scholar : PubMed/NCBI

26 

Jin T, Yang L, Chang C, Luo H, Wang R, Gan Y, Sun Y, Guo Y, Tang R, Chen S, et al: HnRNPA2B1 ISGylation regulates m6A-Tagged mRNA selective export via ALYREF/NXF1 complex to foster breast cancer development. Adv Sci (Weinh). 11:e23076392024. View Article : Google Scholar : PubMed/NCBI

27 

Qiao Y, Sun Q, Chen X, He L, Wang D, Su R, Xue Y, Sun H and Wang H: Nuclear m6A reader YTHDC1 promotes muscle stem cell activation/proliferation by regulating mRNA splicing and nuclear export. Elife. 12:e827032023. View Article : Google Scholar : PubMed/NCBI

28 

Alarcón CR, Goodarzi H, Lee H, Liu X, Tavazoie S and Tavazoie SF: HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell. 162:1299–1308. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Wang X, Lu Z, Gomez A, Hon GC, Yue Y, Han D, Fu Y, Parisien M, Dai Q, Jia G, et al: N6-methyladenosine-dependent regulation of messenger RNA stability. Nature. 505:117–120. 2014. View Article : Google Scholar :

30 

Bokar JA, Shambaugh ME, Polayes D, Matera AG and Rottman FM: Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA. 3:1233–1247. 1997.PubMed/NCBI

31 

Zaccara S, Ries RJ and Jaffrey SR: Reading, writing and erasing mRNA methylation. Nat Rev Mol Cell Biol. 20:608–624. 2019. View Article : Google Scholar : PubMed/NCBI

32 

Zeng Y, Luo Y, Zhao K, Liu SS, Wu KK, Wu YY, Du KK, Pan W, Dai Y, Liu Y, et al: m6A-mediated induction of 7-dehydrocholesterol reductase stimulates cholesterol synthesis and cAMP signaling to promote bladder cancer metastasis. Cancer Res. 84:3402–3418. 2024. View Article : Google Scholar : PubMed/NCBI

33 

Wang J, Fan P, Shen P, Fan C, Zhao P, Shen Y, Dong K, Ling R, Chen S and Zhang J: XBP1s activates METTL3/METTL14 for ER-phagy and paclitaxel sensitivity regulation in breast cancer. Cancer Lett. 596:2168462024. View Article : Google Scholar : PubMed/NCBI

34 

Li T, Hu PS, Zuo Z, Lin JF, Li X, Wu Q, Chen ZH, Zeng ZL, Wang F, Zheng J, et al: METTL3 facilitates tumor progression via an m(6)A-IGF2BP2-dependent mechanism in colorectal carcinoma. Mol Cancer. 18:1122019. View Article : Google Scholar : PubMed/NCBI

35 

Wang Q, Guo X, Li L, Gao Z, Su X, Ji M and Liu J: N(6)-methyladenosine METTL3 promotes cervical cancer tumorigenesis and Warburg effect through YTHDF1/HK2 modification. Cell Death Dis. 11:9112020. View Article : Google Scholar : PubMed/NCBI

36 

Wang J, Yu H, Dong W, Zhang C, Hu M, Ma W, Jiang X, Li H, Yang P and Xiang D: N6-Methyladenosine-Mediated Up-Regulation of FZD10 regulates liver cancer stem cells' properties and lenvatinib resistance through WNT/β-catenin and hippo signaling pathways. Gastroenterology. 164:990–1005. 2023. View Article : Google Scholar : PubMed/NCBI

37 

Wei X, Huo Y, Pi J, Gao Y, Rao S, He M, Wei Q, Song P, Chen Y, Lu D, et al: METTL3 preferentially enhances non-m(6)A translation of epigenetic factors and promotes tumourigenesis. NaT cell Biol. 24:1278–1290. 2022. View Article : Google Scholar : PubMed/NCBI

38 

Xu X and Li Y, Wu Y, Wang M, Lu Y, Fang Z, Wang H and Li Y: Increased ATF2 expression predicts poor prognosis and inhibits sorafenib-induced ferroptosis in gastric cancer. Redox Biol. 59:1025642023. View Article : Google Scholar

39 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

40 

He Z, Jiao H, An Q, Zhang X, Zengyangzong D, Xu J, Liu H, Ma L and Zhao W: Discovery of novel 4-phenylquinazoline-based BRD4 inhibitors for cardiac fibrosis. Acta Pharm Sin B. 12:291–307. 2022. View Article : Google Scholar : PubMed/NCBI

41 

Zheng Z, Lin F, Zhao B, Chen G, Wei G, Chen X, Nie R, Zhang R, Zhao Z, Zhou Z, et al: ALKBH5 suppresses gastric cancer tumorigenesis and metastasis by inhibiting the translation of uncapped WRAP53 RNA isoforms in an m6A-dependent manner. Mol Cancer. 24:192025. View Article : Google Scholar : PubMed/NCBI

42 

Wei J, Yin Y, Zhou J, Chen H, Peng J, Yang J and Tang Y: METTL3 potentiates resistance to cisplatin through m(6) A modification of TFAP2C in seminoma. J Cell Mol Med. 24:11366–11380. 2020. View Article : Google Scholar : PubMed/NCBI

43 

Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Yang TH, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA, et al: The immune landscape of cancer. Immunity. 48:812–830.e814. 2018. View Article : Google Scholar : PubMed/NCBI

44 

Arribas J, Giménez E, Marcos R and Velázquez A: Novel antiapoptotic effect of TBX15: overexpression of TBX15 reduces apoptosis in cancer cells. Apoptosis. 20:1338–1346. 2015. View Article : Google Scholar : PubMed/NCBI

45 

Ogawa S, Kubo H, Murayama Y, Kubota T, Yubakami M, Matsumoto T, Ohashi T, Okamoto K, Kuriki Y, Hanaoka K, et al: Matrix metalloprotease-14 is a target enzyme for detecting peritoneal metastasis in gastric cancer. Photodiagnosis Photodyn Ther. 35:1024202021. View Article : Google Scholar : PubMed/NCBI

46 

Kasurinen A, Gramolelli S, Hagström J, Laitinen A, Kokkola A, Miki Y, Lehti K, Yashiro M, Ojala PM, Böckelman C and Haglund C: High tissue MMP14 expression predicts worse survival in gastric cancer, particularly with a low PROX1. Cancer Med. 8:6995–7005. 2019. View Article : Google Scholar : PubMed/NCBI

47 

Chen WC, Chang AC, Tsai HC, Liu PI, Huang CL, Guo JH, Liu CL, Liu JF, Thuong LHH and Tang CH: Bone sialoprotein promotes lung cancer osteolytic bone metastasis via MMP14-dependent mechanisms. Biochem Pharmacol. 211:1155402023. View Article : Google Scholar : PubMed/NCBI

48 

Chen M, Qu H, Liang X, Huang Y, Yang Z, Lu P, Shi K, Chen P, Zhang Y, Zhou H, et al: Brachyury promotes proliferation and migration of colorectal cancer cells by targeting MMP14. Cancer Cell Int. 25:1322025. View Article : Google Scholar : PubMed/NCBI

49 

Siska PJ, Singer K, Evert K, Renner K and Kreutz M: The immunological Warburg effect: Can a metabolic-tumor-stroma score (MeTS) guide cancer immunotherapy? Immunol Rev. 295:187–202. 2020. View Article : Google Scholar : PubMed/NCBI

50 

DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N and Coussens LM: CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 16:91–102. 2009. View Article : Google Scholar : PubMed/NCBI

51 

Yang H, Zhang Q, Xu M, Wang L, Chen X, Feng Y, Li Y, Zhang X, Cui W and Jia X: CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis. Mol Cancer. 19:412020. View Article : Google Scholar : PubMed/NCBI

52 

Qian J, Li J, Ma H and Ji W: Exosomal circ-ADRM1 promotes lung adenocarcinoma progression and induces macrophage M2 polarization through regulating MMP14 mRNA and protein. Anticancer Drugs. 34:333–343. 2023. View Article : Google Scholar

53 

Ager EI, Kozin SV, Kirkpatrick ND, Seano G, Kodack DP, Askoxylakis V, Huang Y, Goel S, Snuderl M, Muzikansky A, et al: Blockade of MMP14 activity in murine breast carcinomas: Implications for macrophages, vessels, and radiotherapy. J Natl Cancer Inst. 107:djv0172015. View Article : Google Scholar : PubMed/NCBI

54 

Chen Q, Yin H, Jiang Z, He T, Xie Y, Mao W, Han J, Liu S, Lou W, Wu W, et al: Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer. J Immunother Cancer. 12:e0086942024. View Article : Google Scholar

55 

Wang J, Zheng C, Lu J, Xu X, Xiang G, Li J, Zhang J, Mu X and Lu Q: The mechanism of MMP14-positive tumor-associated fibroblast subsets in inhibiting PD-1 immunotherapy for esophageal cancer through exosomal tsRNA-10522. Funct Integr Genomics. 24:1862024. View Article : Google Scholar

56 

Wang HM, Zhang XH, Ye LQ, Zhang K, Yang NN, Geng S, Chen J, Zhao SX, Yang KL and Fan FF: Insufficient CD100 shedding contributes to suppression of CD8(+) T-cell activity in non-small cell lung cancer. Immunology. 160:209–219. 2020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Hu H, He R, Liu M, Liu X, Ai Q, Chen M, Wang Q, Chen W and Qu W: T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription. Int J Oncol 69: 100, 2026.
APA
Hu, H., He, R., Liu, M., Liu, X., Ai, Q., Chen, M. ... Qu, W. (2026). T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription. International Journal of Oncology, 69, 100. https://doi.org/10.3892/ijo.2026.5913
MLA
Hu, H., He, R., Liu, M., Liu, X., Ai, Q., Chen, M., Wang, Q., Chen, W., Qu, W."T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription". International Journal of Oncology 69.3 (2026): 100.
Chicago
Hu, H., He, R., Liu, M., Liu, X., Ai, Q., Chen, M., Wang, Q., Chen, W., Qu, W."T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription". International Journal of Oncology 69, no. 3 (2026): 100. https://doi.org/10.3892/ijo.2026.5913
Copy and paste a formatted citation
x
Spandidos Publications style
Hu H, He R, Liu M, Liu X, Ai Q, Chen M, Wang Q, Chen W and Qu W: T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription. Int J Oncol 69: 100, 2026.
APA
Hu, H., He, R., Liu, M., Liu, X., Ai, Q., Chen, M. ... Qu, W. (2026). T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription. International Journal of Oncology, 69, 100. https://doi.org/10.3892/ijo.2026.5913
MLA
Hu, H., He, R., Liu, M., Liu, X., Ai, Q., Chen, M., Wang, Q., Chen, W., Qu, W."T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription". International Journal of Oncology 69.3 (2026): 100.
Chicago
Hu, H., He, R., Liu, M., Liu, X., Ai, Q., Chen, M., Wang, Q., Chen, W., Qu, W."T‑box transcription factor 15 regulated by methyltransferase‑like 3‑mediated N6‑methyladenosine modification promotes immune escape and progression of gastric cancer by activating matrix metalloproteinase 14 transcription". International Journal of Oncology 69, no. 3 (2026): 100. https://doi.org/10.3892/ijo.2026.5913
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team