Related Experiment Video
Updated: Jul 12, 2025
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
The RNA m6A-Binding Protein YTHDC1 Is Downregulated and Associated With M2 Macrophage Infiltration in Muscle-Invasive
Lamei Zhao1,2, Dongyan Han2, Jianghua Zhu3
1Shanghai Clinical College, Anhui Medical University, Hefei, China.
Background:
Dysregulation of RNA N6-methyladenosine (m6A) modification is indispensable in tumorigenesis. However, in muscle-invasive bladder cancer (MIBC), the key regulators and mechanisms involved in this process remain largely unknown. This study aimed to screen the key m6A regulators and explore its possible role in MIBC.
Methods:
Aberrantly expressed m6A regulator genes were screened in The Cancer Genome Atlas (TCGA) MIBC cohort (n = 408) and validated using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) specimens collected during this study. Clinicopathological relevance and association with tumor immune infiltration was further assessed.
Results:
We identified that the expression of YT521-B homology-domain-containing protein 1 (YTHDC1), an m6A RNA-binding protein, was downregulated in tumor tissues compared with adjacent noncancerous tissues in the TCGA MIBC cohort and our clinical samples. Low YTHDC1 expression correlated with short patient survival, advanced pathologic stage, lymph node metastasis, basal-squamous molecular subtype, non-papillary histological type, and certain genetic mutations important to MIBC. Remarkably, YTHDC1 expression exhibited negative association with tumor-infiltrating M2 macrophage abundance in MIBC.
Conclusion:
Among m6A regulators, we identified that YTHDC1 was downregulated in MIBC and might play an important role in the pathological process in MIBC, especially tumor microenvironment regulation.
Insights
RNA N6-methyladenosine (m6A) dysregulation is key in cancer. In muscle-invasive bladder cancer (MIBC), YTHDC1 is downregulated, impacting survival and the tumor microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- RNA N6-methyladenosine (m6A) modification is crucial in cancer development.
- Key regulators of m6A in muscle-invasive bladder cancer (MIBC) are largely unknown.
- This study investigates m6A regulators in MIBC.
Purpose of the Study:
- To screen key m6A regulators in MIBC.
- To explore the role of m6A regulators in MIBC pathogenesis.
- To assess the association of m6A regulators with tumor immune infiltration.
Main Methods:
- Screening of aberrantly expressed m6A regulator genes in the TCGA MIBC cohort (n=408).
- Validation using fresh-frozen and formalin-fixed paraffin-embedded (FFPE) clinical specimens.
- Assessment of clinicopathological relevance and association with tumor immune infiltration.
Main Results:
- YT521-B homology-domain-containing protein 1 (YTHDC1) expression was downregulated in MIBC tumor tissues.
- Low YTHDC1 expression correlated with shorter survival, advanced stage, metastasis, basal-squamous subtype, non-papillary type, and specific mutations.
- YTHDC1 expression showed a negative association with M2 macrophage abundance in MIBC.
Conclusions:
- YTHDC1 is downregulated in MIBC among m6A regulators.
- YTHDC1 may play a significant role in MIBC pathology.
- YTHDC1 is implicated in the regulation of the MIBC tumor microenvironment.
