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Published on: April 21, 2015
Comprehensive analysis and experimental confirmation identify ADRM1 plays an oncogenic and immunosuppression role in
Likun Li1, Limin Wang2, Dongxia Cao1
1Department of Urology Surgery, Air Force Hospital of Eastern Theater Command, The Chinese People's Liberation Army, Nanjing, Jiangsu, China.
Background:
Kidney renal clear cell carcinoma (KIRC), as the major type of renal cell carcinoma, remains challenging due to its rapid malignant progression and poor prognosis. Adhesion-regulating molecule 1 (ADRM1) has been implicated in tumor development, yet its specific role in KIRC is poorly understood.
Methods:
ADRM1 expression was analyzed using TCGA datasets and the CPTAC database. The differences in ADRM1 expression and its association with survival outcomes were investigated. The correlation of genetic alteration status with ADRM1 expression was studied. The effect of ADRM1 on immune infiltration was examined using R packages. Clinical samples were validated via qPCR and Western blot. In vitro functional assays assessed proliferation of KIRC cells. Transcriptional factors that regulated ADRM1 was confirmed by luciferase reporter gene assay. GSEA and experimental confirmation explored molecular pathways.
Results:
ADRM1 expression was significantly upregulated in KIRC, compared to normal tissues. The expression of ADRM1 was associated with high stages and poor prognosis of KIRC patients. The methylation level was positively associated with the expression of ADRM1 and indicated better survival outcomes. Overexpression of ADRM1 significantly promoted the proliferation of KIRC cells, while ADRM1 knockdown inhibited the proliferation of KIRC cells. ADRM1 expression was regulated by transcriptional factor CTCF. Moreover, ADRM1 promoted the proliferation of KIRC cells via ERK pathway. Immune analysis showed ADRM1 positively correlated with immune checkpoint genes (CTLA-4 and LAG3) and influenced Treg cells.
Conclusions:
ADRM1 is transcriptionally regulated by CTCF and promotes KIRC proliferation through ERK pathway and has prognostic predictive value. It may become a novel therapeutic target for KIRC patients.
Insights
Adhesion-regulating molecule 1 (ADRM1) promotes kidney renal clear cell carcinoma (KIRC) proliferation via the ERK pathway. Upregulated ADRM1 expression is linked to poor prognosis, suggesting it as a potential therapeutic target for KIRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Kidney renal clear cell carcinoma (KIRC) is a major cancer type with challenging progression and poor prognosis.
- The role of Adhesion-regulating molecule 1 (ADRM1) in KIRC development is not well understood.
Purpose of the Study:
- To investigate the expression, function, and prognostic value of ADRM1 in KIRC.
- To explore the regulatory mechanisms and signaling pathways involving ADRM1 in KIRC.
Main Methods:
- Analysis of TCGA and CPTAC datasets for ADRM1 expression and survival association.
- In vitro functional assays (qPCR, Western blot, proliferation assays) and luciferase reporter gene assays.
- Examination of immune infiltration and molecular pathways (GSEA, ERK pathway analysis).
Main Results:
- ADRM1 is significantly upregulated in KIRC and associated with advanced stages and poor prognosis.
- ADRM1 overexpression promotes KIRC cell proliferation, regulated by CTCF via the ERK pathway.
- ADRM1 correlates with immune checkpoint genes and influences Treg cells.
Conclusions:
- ADRM1, regulated by CTCF, promotes KIRC proliferation via the ERK pathway.
- ADRM1 serves as a prognostic biomarker and potential therapeutic target for KIRC.
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