H19/hsa-miR-324-3p/THY1 CeRNA axis affects gastric cancer development by regulating "Integrin beta-2" signaling pathway: bioinformatics gene expression profiling and RNA interaction analysis
H19/hsa-miR-324-3p/THY1 CeRNA axis affects gastric cancer development by regulating "Integrin beta-2" signaling pathway: bioinformatics gene expression profiling and RNA interaction analysis
Golnar Chapnevis,1Mohammad Rezaei,2Mansoureh Azadeh,3,*
1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran 2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran 3. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
Introduction: Although fewer people have been diagnosed with Gastric Cancer (GC) in the last 50 years, it is still one of the most common cancers worldwide. The incidence of this cancer has declined due to a better diet and successful treatment of H.pylori infection. One of the principal challenges in GC treatment is early diagnosis to increase the survival rate. To be more specific, the pre-metastatic diagnosis survival rate is over twice the metastatic survival rate. Therefore, utilizing reliable biomarkers would highly improve the prognosis and treatment of this illness.
Defining a competitive endogenous RNA (CeRNA) network provides valuable biomarkers and boosts the treatment process. CeRna theory claims that RNAs compete for a limited number of miRNAs; this competition affects the regulation of the cell. In cancer, the relationship between the components of this network changes (compared to the normal condition) and provides valuable information about the disease and its stage.
This study has employed bioinformatics analysis using RStudio to target novel biomarkers for diagnosis and curing CG.
Methods: First, GSE79973 raw data was downloaded from Gene Expression Omnibus (GEO). Using RStudio, an in-depth analysis was performed to obtain differentially expressed genes. The most significant genes (|logFC| > 2 and adjusted p-value< 0.05) were selected and taken to miRWalk 2.0 to find target miRNAs. To find suitable lncRNAs, miRNAs were searched in LncBase v.3 and several lncRNAs were found. Additionally, to ensure that the lncRNAs are highly significant in Gastric Cancer, the lnCAR database was employed
At last, Cystoscope software 3.8.2 was used to show the interaction between the components of the ceRNA network.
Results: After careful analysis of ten pairs of gastric cancer tissue and adjacent non-tumor mucosa (GSE79973), a total number of 788 differentially expressed genes (DEGs) were detected.
DEGs with adjusted p-value < 0.05 and |logFC| > 2 were considered significant. 20 of the hub genes with the lowest adjusted p-value were taken to miRWalk 2.0. The miRwalk 2.0 database provided target miRNA for the chosen hub genes. Score and number of pairings were considered factors for a suitable miRNA.
THY1(Thy-1 cell surface antigen) demonstrated a connection with hsa-miR-324-3p in miRwalk. The picked miRNA was searched in LncBase v.3 and H19, GAS5, and DLEU2 were found.
To make sure that the lncRNAs are significant in Gastric cancer, lnCAR was used to find the level of expression of lncRNAs.
Then, using TANRIC database the connection of H19 and THY1 was also proved with the correlation of 0.4.
In addition, the BioPlanet 2019 database confirmed that THY1 is a component of Integrin beta-2 pathway which is involved in tumor progression.
Conclusion: According to the previous analysis, there might be a CeRNA network between THY1, H19, and hsa-miR-324-3p. Moreover, the involvement of THY1 in a CeRNA network, as well as a signaling pathway, reinforces the possibility of THY1 being a reliable biomarker for diagnostic and prognostic goals.