In Silico Profiling of Regulatory MicroRNA Targets in Programmed Cell Death 1 Gene

List of genes associated with TCR coinhibation identified in humans were collected from literature and publicly available databases. All the relevant publications were identified after searching PubMed with key words immunotolerence, graft transplant, cancer, materofetal or fetomaternal tolerance, Nivolumab etc. Out of all the genes obtained after keywords searching, PDCD1 was selected for this computational study as previously described study of Rahman et al. (2014).

The sequence of PDCD1 was retrieved from Genbank (NG_012110) (Benson et al., 2000). We used miRDB for searching of potential miRNA targets of PDCD1 gene. miRDB is an online computational tool for miRNA target prediction and functional annotations (Wang, 2008). The miRDB (MicroRNA target prediction and functional study data base http://mirdb.org/) was used for potential miRNA target identification in PDCD1 from NCBI Gene ID and predicts miRNA targets in for human.

By using miRDB bioinformatic database, 26 potential miRNAs targeting PDCD1 gene in human were identified, given in Tables I as previously described study of Rahman et al. (2014) who predicted 11 targeting miRNA of GJB3 gene by using miRDB software. The miRDB is the computer based database for identification binding site in selected gene, which will provide strong further basis for experimental validation (Chen and Wang, 2019) of these novel miRNAs in PDCD1. If validated by experiments, these miRNAs might be used as novel biomarkers for regulation of PDCD1 gene.

Tio et al. (2018) studied anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. They came to know that among 6 patients with solid organ transplant shows graft rejection and including 1 death. Patients with HIV or hepatitis B/C respond well to anti-PD-1/PD-L1 immunotherapeutic treatment without any increased in toxicity.

Guleria and Sayegh (2007) studies that role of PD-1 upon binding with it ligand PD-L1 significantly increase rate of fetal survival due to shifting to Th2 cytokines, which are important for maintenance of successful pregnancy. Compared with the results of current study, PDCD1 may possibly responsible for programmed cell death.

Wang et al. (2017) reviewed that binding of PD1/PDL1 has been considered to play an important role in suppressing immune system which leads to invasion of tumor cells rejection of organ transplant and failure of fetomaternal tolerance. Thus, this study will provide the millstones for future researches to look on putative miRNA of PDCD1 gene.

The miR-661 has been well known to be involved in development of cancer in human beings (Wang et al., 2017). The hsa-miR-661 has helps the proliferation of the human cancerous cell line, this suggested that it may be a potential in therapy of lung cancer (Lu et al., 2019). miR-661 prevents the proliferation of human glioma cells, and their invasion and migration by targeting Telmerase reverse transcriptas TERT/hTERT) (Li et al., 2015). Another previous study reported that miR-661 can promotes the ovarian cancer cells by directing targeting the inositol polyphosphate-5-phosphate J (INPP5j) gene (Zhu et al., 2015).

Apoptosis, a form of program cell death has been studied in many degenerative diseases (Cheng et al. 2011). The downregulation of miR-2861 may prevents the apoptosis of endometriotic tissue through the regulation of the MMp2 and STAT3. So, miR-2861 might be a potential therapeutic biomarker in endometriosis (Yu et al., 2019). The previous study identified the miR-2861 as a regulator of cardiomyocyte necrosis and suggest potential therapeutic biomarker in cardiac disease (Weng et al., 2016). miR-6734 arrested the cellular growth and causes

Table I.- miRNA targeting PDCD1 in human and list of 26 miRNA predicated by online tool miRDB in the sequence of Programmed cell death 1 (PDCD1) gene. Gene 5133 is predicted to be targeted by 26 miRNAs in miRDB.

the apoptosis of colon cancer cells by up-regulating the p-21 genes, which is suggesting the its key role in cancer cell survival and growth.

The miR-342 regulates the lumen formation of mammary gland morphogenesis (Weng et al., 2016). The Polymerase chain reaction (PCR) is a sensitive of molecular identification (Shaukat et al., 2019). Ding et al. (2016) has predicted that differentially expressed miRNAs in type 2 diabetes mellitus (T2DM) including hsa-miR-3960 by real time PCR. Their study might be helpful in subsequent experiments in T2DM.

Details of names of candidate miRNAs, their sequences, order of nucleotides, seed sequences and location target score and protein size of target gene has been shown in Table I, multiple sequence alignment, phylogenetic tree analysis of all the 26 miRNAs and purines and pyrimidines alignment of 26 miRNAs are shown in Supplementary Figure 1. All the miRNA targeting PDCD1 on miRDB were displayed in Tables I and Supplementary Figure 1.

The miRNAs are the novel class of small non-coding RNAs that targets in silencing of one or more genes. Keeping in view of importance of computer based prediction databases miRDB has been used in our study to mine the miRNAs targeting PDCD1 gene in human beings. We have identified 26 specific miRNAs in humans which can target different regions in PDCD1 gene. Our data will provide concrete bases for the validation of these miRNAs in silencing of PDCD1 gene.

There is supplementary material associated with this article. Access the material online at: https://dx.doi.org/10.17582/journal.pjz/20191019021035

Authors have declared no conflict of interest.