Title:Integrated Analysis of the Expression, Involved Functions, and
Regulatory Network of RUNX3 in Melanoma
Volume: 25
Issue: 9
Author(s): Zhang Feng, Yanxin Liu and Huaxia Chen*
Affiliation:
- Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical
University, Jinan 250021, China
Keywords:
Melanoma, RUNX family transcription factor 3, microRNAs, melanogenesis, GSEA, PPI analysis.
Abstract:
Background: As a tumor suppressor or oncogenic gene, abnormal expression of RUNX
family transcription factor 3 (RUNX3) has been reported in various cancers.
Introduction: This study aimed to investigate the role of RUNX3 in melanoma.
Methods: The expression level of RUNX3 in melanoma tissues was analyzed by
immunohistochemistry and the Oncomine database. Based on microarray datasets GSE3189 and
GSE7553, differentially expressed genes (DEGs) in melanoma samples were screened, followed
by functional enrichment analysis. Gene Set Enrichment Analysis (GSEA) was performed for
RUNX3. DEGs that co-expressed with RUNX3 were analyzed, and the transcription factors (TFs)
of RUNX3 and its co-expressed genes were predicted. The protein-protein interactions (PPIs) for
RUNX3 were analyzed utilizing the GeneMANIA database. MicroRNAs (miRNAs) that could
target RUNX3 expression, were predicted.
Results: RUNX3 expression was significantly up-regulated in melanoma tissues. GSEA showed
that RUNX3 expression was positively correlated with melanogenesis and melanoma pathways.
Eleven DEGs showed significant co-expression with RUNX3 in melanoma, for example, TLE4
was negatively co-expressed with RUNX3. RUNX3 was identified as a TF that regulated the
expression of both itself and its co-expressed genes. PPI analysis showed that 20 protein-encoding
genes interacted with RUNX3, among which 9 genes were differentially expressed in melanoma,
such as CBFB and SMAD3. These genes were significantly enriched in transcriptional regulation
by RUNX3, RUNX3 regulates BCL2L11 (BIM) transcription, regulation of I-kappaB kinase/NFkappaB
signaling, and signaling by NOTCH. A total of 31 miRNAs could target RUNX3, such as
miR-326, miR-330-5p, and miR-373-3p.
Conclusion: RUNX3 expression was up-regulated in melanoma and was implicated in the
development of melanoma.