ADCY5 act as a putative tumor suppressor in glioblastoma: An integrated analysis
Wang Can1, Wen Yan2, Huang Luo1
1Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, 400030, China.
Background:
Adenylyl cyclase (AC) isoforms played a key role in the multiple cancer pathology, However, the expression, prognostic value and function of ADCY5 in Glioblastoma (GBM) have not been reported yet. This research intends to discover the expression, epigenetic alteration and biological function of ADCY5 in GBM and its value on patients' prognosis.
Methods:
① Transcriptional level, epigenetic alteration, prognostic value and molecular network of ADCY5 were analyzed by using of public online datasets. ② The mRNA expression profile of ADCY5 was explored by using GEPIA database and protein expression levels were detected by HPA Database. ③ The prognostic value of ADCY5 was determined by Kaplan-Meier Plotter, GEPIA and CGGA database. ④ The epigenetic characteristics of ADCY5 were determined by DiseaseMeth database. ⑤ Identification of genes co-expressed with ADCY5 and potential mechanism analyses were performed by using DAVID cBioPorta and STRING. ⑥ Reverse transcription-polymerase chain reaction (RT-PCR), cell counting kit-8 (CCK-8), colony formation, wound-healing scratch and transwell assay were applied to detect relative mRNA expression and biological function of ADCY5 in GMB cells.
Results:
ADCY5 mRNA and protein were downregulated in GBM compared with normal tissues. Analysis of the genetics and epigenetics of ADCY5 suggested that its expression was negatively correlated with DNA methylation. High expression of ADCY5 was significantly associated with age, grade, IDH mutation, 1p19q_codeletion, radiotherapy and chemotherapy and acted as an independent prognostic factor in GBM. ADCY5 mRNA also down-expressed in GBM cell lines and re-expressed of ADCY5 could inhibit cell proliferation, viability, migration/invasion and epithelial-mesenchymal transition (EMT) in vitro. In the analysis of genes co-expressed with ADCY5, we found that cAMP/AKT pathway, cGMP-PKG pathway, Wnts pathway were dissimilarly enriched.
Conclusion:
Our study indicated that ADCY5 could act as an epigenetic biomarker in GBM, as well as a prognosis target in patients with GBM.
Insights
Adenylyl cyclase 5 (ADCY5) is downregulated in Glioblastoma (GBM) and linked to poorer prognosis. Restoring ADCY5 inhibits GBM cell growth and invasion, suggesting its potential as a biomarker and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Adenylyl cyclase (AC) isoforms are implicated in cancer.
- The role of ADCY5 in Glioblastoma (GBM) remains uncharacterized.
- This study investigates ADCY5 expression, epigenetic alterations, and prognostic significance in GBM.
Purpose of the Study:
- To determine the expression profile of ADCY5 in GBM.
- To analyze the prognostic value and epigenetic regulation of ADCY5 in GBM.
- To elucidate the functional role of ADCY5 in GBM cell behavior.
Main Methods:
- Bioinformatic analysis of public datasets (GEPIA, HPA, Kaplan-Meier Plotter, CGGA, DiseaseMeth, cBioPortal, STRING).
- In vitro experiments including RT-PCR, CCK-8, colony formation, wound healing, and Transwell assays.
- Analysis of ADCY5 co-expressed genes and associated signaling pathways (cAMP/AKT, cGMP-PKG, Wnts).
Main Results:
- ADCY5 mRNA and protein expression are downregulated in GBM tissues and cell lines.
- ADCY5 expression is negatively correlated with DNA methylation and associated with clinical parameters.
- High ADCY5 expression serves as an independent prognostic factor in GBM.
- ADCY5 re-expression inhibits GBM cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
Conclusions:
- ADCY5 functions as a potential epigenetic biomarker in GBM.
- ADCY5 represents a promising prognostic target for GBM patients.
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