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Oncogenic role of SKA2 and its ceRNA network in hepatocellular carcinoma based on a comprehensive analysis
Wanxue Hu1, Xiaoyi Hu2, Yongchao Zhu1
1Department of Clinical Laboratory, Hua County People's Hospital, Anyang, China.
Background:
Genetic alterations have important roles in cancer development and progression. SKA2 (spindle and kinetochore associated complex subunit 2) is a mitotic component that plays a critical role in maintaining the silence of the metaphase plate and spindle checkpoint. However, the exact role of SKA2 in hepatocellular carcinoma (HCC) remains unclear. The current study aimed to comprehensively identify the function of SKA2 in HCC.
Methods:
We utilized various databases and bioinformatics tools, such as The Cancer Genome Atlas (TCGA), survminer package, Tumor Immune Estimation Resource (TIMER), cBioPortal website, clusterProfiler package, gene set enrichment analysis (GSEA), miRWalk, TargetScanHuman8.0, miRDB, DIANA and Cytoscape to identify the role of SKA2 in HCC.
Results:
Our results showed that patients with HCC exhibited a high SKA2 expression. Further, the SKA2 high expression group had a worse overall survival (OS). And SKA2 was associated with tumor stage and the immune system. In addition, 188 co-expression genes of SKA2 participated in some processes including cell cycle, DNA replication and so on. The tumor had a lower hsa-miR-19b-1-5p and hsa-miR-378a-5p expression, and these two microRNAs (miRNAs) were also correlated with OS. SNHG14, SNHG15, and SPCA6P-AS were significantly negatively correlated with hsa-378a-5p, and these three long non-coding RNAs (lncRNAs) showed a positive correlation with SKA2 (P<0.05). SKA2 is a member of competing endogenous RNA (ceRNA). Moreover, it is related to SPACA6P-AS/hsa-miR-378a-5p/SKA2, SNHG14/hsa-miR-378a-5p/SKA2, and SNHG15/hsa-miR-378a-5p/SKA2, which play significant roles in tumor progression.
Conclusions:
SKA2 is associated with OS, tumor stage, and immune infiltrating cells in HCC. Thus, we propose that SKA2 functions as a ceRNA and influences tumorigenesis. These findings lay the foundation for future research in the field of HCC.
Insights
High SKA2 expression in hepatocellular carcinoma (HCC) correlates with poor survival and advanced tumor stage. SKA2 acts as a competing endogenous RNA (ceRNA), influencing HCC progression through specific microRNA and long non-coding RNA interactions.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Genetic alterations drive cancer development and progression.
- SKA2 (spindle and kinetochore associated complex subunit 2) is crucial for mitotic regulation.
- The specific role of SKA2 in hepatocellular carcinoma (HCC) requires elucidation.
Purpose of the Study:
- To comprehensively investigate the functional role of SKA2 in hepatocellular carcinoma (HCC).
- To explore the association of SKA2 expression with patient survival and clinicopathological features in HCC.
- To identify potential molecular mechanisms, including ceRNA networks, involving SKA2 in HCC.
Main Methods:
- Utilized TCGA, TIMER, cBioPortal, and other bioinformatics tools for comprehensive analysis.
- Analyzed SKA2 expression, overall survival (OS), and correlations with tumor stage and immune infiltration.
- Investigated co-expressed genes, microRNA (miRNA) interactions, and long non-coding RNA (lncRNA) networks using miRWalk, TargetScanHuman8.0, miRDB, DIANA, and Cytoscape.
Main Results:
- Elevated SKA2 expression was observed in HCC patients, correlating with worse OS and advanced tumor stage.
- SKA2 expression was significantly associated with immune cell infiltration.
- Identified 188 co-expressed genes involved in cell cycle and DNA replication; elucidated a ceRNA network involving SPACA6P-AS/hsa-miR-378a-5p/SKA2, SNHG14/hsa-miR-378a-5p/SKA2, and SNHG15/hsa-miR-378a-5p/SKA2.
Conclusions:
- SKA2 is a prognostic biomarker in HCC, linked to tumor stage and immune microenvironment.
- SKA2 functions as a competing endogenous RNA (ceRNA), playing a significant role in HCC tumorigenesis.
- These findings provide a foundation for future therapeutic strategies targeting SKA2 in HCC.
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