Dysregulation of CCL5 in a ceRNA network promote T-cell prolymphocytic leukemia in the G alpha and interleukin 10 signaling pathway: integrated bioinformatics and system biology analysis
Dysregulation of CCL5 in a ceRNA network promote T-cell prolymphocytic leukemia in the G alpha and interleukin 10 signaling pathway: integrated bioinformatics and system biology analysis
fatemeh tavakoli kia,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: T-cell prolymphocytic leukemia (T-PLL) is an extremely rare type of leukemia with a high mortality rate. This malignancy characterized by the out-of-control growth of mature T- lymphocytes.t-pll accounts for 2 % of mature lymphocytic leukemia in adults, commonly patients over 65. even so, T_PLL is more heterogeneous and includes a wide range of clinical, morphological, and molecular characteristics, which sometimes makes diagnosis difficult.
recent treatments don’t have satisfying progress thus we need new treatment and cure. The main aim of this study is to find the potential biomarker and pathway to diagnose the malignancy in early stage.
Methods: For the start , the suitable GSE(GSE147930), gene expression profile, has been extracted from NCBI Gene Expression Omnibus(GEO) and analyzed by R studio so as to show gene expression profile (fig.4) and determine the gene which features a significant up and down expression regulation (fig.5). Ccl5 gene has been chosen since of its critical up regulation in tpll cells (fig.6).
Moreover, the Free Online prediction software miRWalk 3.0 has been used to discover related miRNAs for ccl5 . After that to find lncRNAs which associated with miRNAs, the experimental and predictive DIANA LncBase v.2 modules were utilized.
Results: Based on GSE147930 , 416 up and down regulated gene were determined. Ccl5 up regulated gene were selected among these ups and down which has a interaction in G Alpha signaling , class A/1 and interleukin 10 signaling pathway (fig.8-10).
hsa-miR-150-5p, hsa-miR-3667-3p, hsa-miR-20a-5p and hsa-miR-335-3p miRNAs were extracted from miRWalk 3.0. in addition HCG11, HCG18, SNHG14, ZNF883 and CASC9 LncRNAs were sponged by these miRNAs that were extracted from experimental and predictive DIANA LncBase v.2 modules.
As a result these miRNAs and lncRNAs can act as a ceRNA network which has a effect on ccl5 gene regulation
Conclusion: To sum up our result, the mentioned lncRNAs (HCG11, HCG18, SNHG14, ZNF883 and CASC9 ) in ceRNA network can be used as a ccl5 expression regulator in tpll by having a major effect on hsa-miR-150-5p, hsa-miR-3667-3p, hsa-miR-20a-5p and hsa-miR-335-3p miRNAs which end up affecting G Alpha signaling , class A/1 and interleukin 10 signaling pathway. All these events can promote tpll in T-cell. Thus, these finding could provide a new therapy method and diagnose the malignancy in early stage.