Abstract
The AT-hook transcription factor, AKNA, is a nuclear protein that affects a few physiological and pathological processes including cancer. Here, we investigated the role of AKNA in gastric cancer (GC). By using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, AKNA was found deregulated in both GC cell lines and 32 paired GC tissues. Subsequently, Kaplan-Meier analysis and clinicopathological analysis were conducted using both 32 GC cases' data above and RNA-Seq data of AKNA in 354 GC patients and the corresponding clinical-pathological data obtained from The Cancer Genome Atlas (TCGA), and AKNA expression was found closely related to location, metastasis, and TNM staging of GC. Then, the potential molecular mechanisms of AKNA in GC were explored by gene set enrichment analysis (GSEA), qRT-PCR, and Western blot assays. AKNA was found to be a hub gene related to homotypic cell to cell adhesion, regulation of cell to cell adhesion, leukocyte cell to cell adhesion, and regulation of T cell proliferation in GC. GO analysis revealed that AKNA involved in the regulation of epithelial-mesenchymal transition (EMT)-related pathways including chemokine signaling pathway, cytokine to cytokine receptor interaction, cell adhesion molecules, and jak-stat signaling pathway in GC. To explore the regulation of AKNA expression, Targetscan and TargetMiner were used to predict the possible miRNA which targeted AKNA and found the expression of AKNA was negatively correlated to miR-762 which could be sponged by circTRNC18. In conclusion, AKNA could function as a tumor suppressor by modulating EMT-related pathways in GC. The expression of AKNA might be regulated by circTRNC18/miR-762 axis. AKNA could serve as a potential biomarker and an effective target for GC diagnosis and therapy.
Highlights
Gastric cancer (GC) is the fifth most frequent malignancies and the third most frequent cause of cancer-related death all over the world [1]
Expression of AKNA Was Diminished in GC. quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of AKNA in GC cell lines and 32 paired GC tissues
The results showed that the expression of AKNA was significantly deregulated in GC cells compared to GES-1 (Figure 1(a))
Summary
Gastric cancer (GC) is the fifth most frequent malignancies and the third most frequent cause of cancer-related death all over the world [1]. An improved understanding on the underlying mechanisms of the EMT involved in the process of GC metastasis is urgently needed for elucidating the development of relevant therapeutic approaches. Single-nucleotide polymorphisms (SNPs) make AKNA a susceptibility genetic factor [5]. AKNA directly binds the A/T-rich promoters regions of CD40 and CD40 ligand (CD40L) and coordinately regulates their expression, thereby activate antitumor immune response, while HPV E6, a cervical cancer-related oncoprotein, could downregulate AKNA and lead to the progression of cancer [6, 7]. By using weighted gene coexpression network analysis (WGCNA), AKNA was found to be a hub gene of head and neck squamous cell carcinoma (HNSCC) which is related to the immune response [8]
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