miRNA/lncRNA axis of a ceRNA network promotes the development of FL cancer by regulating Wnt signaling pathway: an integrated bioinformatics and systems biology analysis
miRNA/lncRNA axis of a ceRNA network promotes the development of FL cancer by regulating Wnt signaling pathway: an integrated bioinformatics and systems biology analysis
Arian Sadeghi,1Mohammad Rezaei ,2Mansoureh Azadeh,3,*
1. Zist Fanavari Novin Biotechnology Institute 2. Zist Fanavari Novin Biotechnology Institute 3. Zist Fanavari Novin Biotechnology Institute
Introduction: Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for about 10-20% of all lymphomas in western countries. The median age at diagnosis is 60 years old and there is a slight predominance in women . Bone marrow involvement is present in more than 50% of patients. The disease is usually characterized by an indolent clinical course response to initial therapy with frequent relapses and shorter duration responses to salvage therapy.
Methods: To start, NCBI Gene Expression Omnibus (GEO) has been chosen to get the Proper GSE, A related gene expression profile has been downloaded and analyzed by Rstudio in order to find the genes which have notable up and down expression regulations, that by analysis of candidate genes’ pathways, HAPLN1, SFRP2, and SFRP4 has been selected. Moreover, miRWalk and miRTarBase databases have been used to identify numerous target microRNAs of selected genes. Eventually, by analyzing pathways involved in FL, the required microRNA has been selected. By examination of related lncRNAs, since MALAT-1 lncRNA had the most reliance and specificity, it has been selected as another axis of our ceRNA network.
Results: Based on GEO analysis the desired GSE named GSE152068 was indicated among human stromal cells isolated from Follicular lymphoma (FL) or non-malignant reactive (RLN) lymph nodes. These analysis outcomes assigned that the GSE152068 was surprisingly enriched in several biological mechanisms. A total number of 12 up-regulated and 8 down-regulated genes from the GSE was indicated which by the Enrichr database the pathways of each were examined separately. Up-regulated genes pointed to related pathways named, Wnt signaling pathway and Interleukin-1 regulation of extracellular matrix that HAPLN1, SFRP2, and SFRP4 demonstrated a notable gene of these pathways.
Conclusion: According to the all mentioned events, concluded that hsa-let-7a-5p via overexpression of the HAPLN1 gene’s function acts as a tumor growth factor in the Wnt signaling pathway of FL and AML. Thus, these findings could provide promising comorbidity between these two types of cancer and their effect on each other. It also can lead us to a common method for the treatment of FL and AML patients.
Keywords: Follicular lymphoma- Systems biology - MALAT1- ceRNA network-HAPLN1