title: AKT1 as the PageRank hub gene is associated with melanoma and its functional annotation is highly related to the estrogen signaling pathway that may regulate the growth of melanoma.
abstract: In order to detect the disease-associated genes and their gene interaction function and association with melanoma mechanisms, we identified a total of 1,310 differentially expressed genes (DEGs) from the Gene Expression Omnibus database GSE3189 with FDR <0.01 and |logFC| >2 using the R package. After constructing the gene interaction network by STRING with the selected DEGs, we applied a statistical approach to identify the topological hub genes with PageRank score. Forty-four genes were identified in this network and AKT1 was selected as the most important hub gene. The AKT1 gene encodes a serine‑threonine protein kinase (AKT). High expression of AKT is involved in the resistance of cell apoptosis as well as adaptive resistance to treatment in melanoma. Our results indicated that AKT1 with a higher expression in melanoma showed enriched binding sites in the negative regulation of response to external stimulus, which enables cells to adapt to changes in external stimulation for survival. Another finding was that AKT regulated the lipid metabolic process and may be involved in melanoma progression and promotion of tumor growth through gene enrichment function analysis. Two highlighted pathways were detected in our study: i) the estrogen signaling pathway modulates the immune tolerance and resistance to cell apoptosis, which contributes to the growth of melanoma and ii) the RAP1 signaling pathway which regulates focal adhesion (FA) negative feedback to cell migration and invasion in melanoma. Our studies highlighted the top differentially expressed gene AKT1 and its correlation with the estrogen signaling and RAP1 signaling pathways to alter the proliferation and apoptosis of melanoma cells. Analysis of the enrichment functions of genes associated with melanoma will help us find the exact mechanism of melanoma and advance the full potential of newly targeted cancer therapy.
authors: Key Laboratory of Advanced Control and Optimization for Chemical Processes of the Chinese Ministry of Education, East China University of Science and Technology, Shanghai 200237, P.R. China.
authors: Jingjing
authors: J
authors: Zhao
authors: Department of Dermatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, P.R. China.
authors: Xue
authors: X
authors: Zeng
authors: Department of Dermatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, P.R. China.
authors: Ping
authors: P
authors: Song
authors: Department of Dermatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, P.R. China.
authors: Xiaohong
authors: X
authors: Wu
authors: Key Laboratory of Advanced Control and Optimization for Chemical Processes of the Chinese Ministry of Education, East China University of Science and Technology, Shanghai 200237, P.R. China.
authors: Hongbo
authors: H
authors: Shi
mesh_terms: D004967:Estrogens / Q000378:metabolism; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D000089804:Shelterin Complex; D015398:Signal Transduction / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034501:Telomere-Binding Proteins / Q000378:metabolism; D059467:Transcriptome
chemical_list: D004967:Estrogens; D011960:Receptors, Estrogen; D000089804:Shelterin Complex; C440809:TERF2IP protein, human; D034501:Telomere-Binding Proteins; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt