bahram mohammad soltani

Cisplatin resistance presents a considerable hurdle in the treatment of ovarian cancer, significantly impacting patient outcomes and limiting the effectiveness of chemotherapy. This study employs advanced bioinformatics techniques-including RNA sequencing (RNA-seq), DNA sequencing (DNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq)-to elucidate the molecular mechanisms underlying this resistance, with a particular focus on the long non-coding RNA (lncRNA) LINC02381. Our findings reveal that LINC02381 is significantly upregulated in ovarian cancer cells exhibiting resistance to cisplatin, suggesting its pivotal role in mediating this phenomenon. We further demonstrate that cytokines, particularly interleukin-12 (IL-12), secreted by immune cells within the tumor microenvironment, activate the Wnt signaling pathway. This activation leads to the binding of the transcription factor TCF7 to the promoter region of LINC02381, resulting in enhanced expression of this lncRNA. Notably, this interaction establishes a positive feedback loop in which LINC02381 not only promotes its own expression but also amplifies Wnt signaling activity. This cascade ultimately drives the upregulation of ATP-binding cassette (ABC) transporters, which are crucial for the efflux of cisplatin from cancer cells. Thus, the drug's intracellular concentration is reduced, and cell survival under chemotherapy pressure is facilitated. These insights uncover a novel mechanism of cisplatin resistance driven by the IL-12/Wnt/TCF7/LINC02381 axis, highlighting the complex interplay between immune signaling and drug resistance in ovarian cancer. Our findings suggest that targeting this regulatory pathway may offer promising therapeutic strategies to overcome chemotherapy resistance, paving the way for improved treatment outcomes in patients with ovarian cancer. Future research should focus on validating these mechanisms and exploring potential interventions that disrupt this feedback loop.

Resistance to chemotherapy drugs always has been an obstacle in the definitive treatment of cancers. Therefore, the discovery of molecular events leading to drug resistance improves therapeutic methods. Non-coding RNAs (ncRNAs) are a group of molecules that regulate intracellular events, including carcinogenesis and drug resistance pathways. For example, the competitive network of endogenous ncRNAs (ceRNA) regulates the mRNA expression of target genes by binding to miRNAs and limiting their regulatory effect. So far, limited studies have been reported on the role of ceRNA in drug resistance in ovarian cancer. In this study, large-scale RNAseq sequencing data obtained from cisplatin-resistant and sensitive cells were used to search for ceRNAs that are possible regulators of drug resistance in ovarian cancer. For this purpose, the A2780 sensitive and resistant cisplatin ovarian cancer cell line was selected, and the SRA data prepared by RNAseq method was screened. During this process, lncRNAs, microRNAs and mRNAs with expression changes were separated and classified. In the bioinformatic analysis of resistant and sensitive cells, 16 mRNAs, 10 lncRNAs, and 149 miRNAs were overexpressed, and 622 mRNAs, 263 lncRNAs, and 177 miRNAs were underexpressed. These genes were involved in 57 cellular pathways, and by mapping the regulatory ceRNA network, ZNRF3-AS1-miR-33-DUSP1 and ZNRF3-AS1-miR33-HSPA2 axes were identified as potential ceRNA networks involved in cisplatin-resistant ovarian cancer.

In this article published in Cell J, Vol 19, No 4, Jan-Mar (Winter) 2018, on pages 654-659, the authors found that Figures 2 and 3 had some errors that accidentally happened during organizing figures. Because of mislabeling some images and saving them in an incorrect folder, the following figures' legends are corrected.
The authors would like to apologize for any inconvenience.

Cancer is one of the most challenging diseases in the world. It is widely accepted that knowing the molecular aspects of diseases, including cancers, helps to develop methods for their therapy and diagnosis. Long non-coding RNAs (lncRANs) are a novel category of regulatory genes known to be involved in cancer incidence. The expression of these genes is said to be suitable of using in prognosis, diagnosis, targeted therapy, etc. The RT-qPCR method that is widely used for analyzing the gene expression requires the application of appropriate reference genes as the internal control. The expression status of a proper housekeeping reference gene is not supposed to change under experimental circumstances. This study aimed to find a suitable reference gene in the U87 cells after overexpression of a gene of interest. To this aim, the expression status of four common reference genes (ACTB, β2M, GAPDH, and HPRT1) was examined in the transfected U87 cells. The U87 cells were transfected with a vector overexpressing YWHAE-lncRNA and an empty vector (mock). After total RNA extraction and cDNA synthesis, RT-qPCR was applied using the aforementioned internal control genes. Data were analyzed, and their graphs were plotted in GraphPad Prism 8.2 software. Β2M showed the most change; accordingly, GAPDH and HPRT1 expression levels were changed about 5 and 4 times, respectively. Of the candidate genes, only the ACTB gene had a consistent expression level in two different modes of transfection, and therefore, it is suggested as an appropriate reference gene for the study of gene expression in the transfected U87 cell line. It is remained to be tested if β2M, GAPDH, and HPRT1 common internal controls are specifically affected by YWHAE-lncRNA overexpression or other lncRNAs may affect their expression as well.

MicroRNAs (miRNAs) are short non-coding RNAs that play a role in post-transcriptional regulation of gene expression. Hsa-miR-11181 was originally introduced as a regulator of genes involved in some brain tumours. Due to the high expression of Hsa-miR-11181 in limited glioblastoma brain tumours, in this study we intend to assess the expressions of Hsa-miR-11181 and Has-miR11181-3p in brain tumour tissues and attribute new target genes to these miRNAs.

In this experimental study, total RNA from brain tissue samples was extracted for real-time quantitative polymerase chain reaction (RT-qPCR) analysis after cDNA synthesis. In order to confirm a direct interaction of Hsa-miR-11181 with two target genes, the 3ˊ UTR of AKT2 and transforming growth factor-beta receptor 1 (TGFBR1) were cloned separately for assessment by the dual luciferase assay.

RT-qPCR analysis indicated that both Hsa-miR-11181-5p and Hsa-miR-11181-3p specifically up-regulated in higher grades of glioma tumours versus other brain tumour types. Consistently, lower expression levels of AKT2 and TGFBR1 were detected in higher grade gliomas compared to other types of brain tumours, which was inverse to the level of expression detected for the heparin-binding EGF-like growth factor (HBEGF) gene. The results of the dual luciferase assay supported a direct interaction of Hsa-miR-11181 with the 3ˊ UTR sequences of the AKT2 and TGFBR1 genes.

Overall, our data suggest that miR-1118 is a potential molecular biomarker for discrimination of glioma brain tumours from other brain tumour types.

Among different roles of miRNAs in AD pathogenesis, hsa-miR-494-3p and hsa-miR-661 functions are poorly understood.

To obtain the gene targets, gene networks, gene ontology, and enrichment analysis of the two miRNAs, some web servers were utilized. Furthermore, the expressions of these miRNAs were analyzed by qRT-PCR in 36 blood sera, including 18 Alzheimer’s patients and 18 healthy individuals.

The in silico analysis demonstrated the highlighted roles of metabolic and cellular response to stress pathways engaged in circulating hsa-miR-494-3p and hsa-miR-661 in AD. The qRT-PCR analysis showed that the downregulated expression level of hsa-miR-661 was statistically significant (p < 0.05). Also, the ROC curve of hsa-miR-661 displayed the significant AUC (p = 0.01).

Based on our findings, the metabolic and cellular responses to stress pathways are closely connected to these two miRNAs functions. Besides, the qRT-PCR and Roc curve determined hsa-miR-661 could be as a biomarker for diagnosis or prognosis of AD patients.

Crown gall is one of the most destructive bacterial diseases of plants. Nowadays, special attention has been focused on the biological control of plant diseases as an alternative to chemical control. This study was conducted to better understanding the molecular mechanism of Surfactin on Agrobacterium tumefaciens as a prerequisite for the use of Bacillus as a biocontrol agent of this pathogen. In this study, Tobacco plants (Nicotiana tabacum), IBRC-M10701 strains of A. tumefaciens, and pure commercial Surfactin (25 µm) were used. miRNAs and lox genes have an important effect in the auxin signalling pathway. Using Real-time PCR, the expression level of miR167 and lox gene measured 1, 3, and 6 days after inoculations in the interaction of A. tumifaciens IBRC-M10701 and Surfactin. The expression level of lox gene in Agrobacterium treatment showed 0.47, 22.9, and 61.8 increased. In Surfactin treatment it was 4.6, 3.6 and, 11.6 fold and in Surfactin-Agrobacterium treatment this amount was 4.2, 38.8, and 20.3 fold. In addition, the expression level of nta-miRNA167 in Agrobacterium treatment indicated an increase of 3.4 and 214.4 fold (in the first and third day after inoculation), then decreased to 2.5 fold (in the sixth day), in treatment with Surfactin the amount of expression level was detected as 3.2, 13.2 and 4.5 fold and in Surfactin-Agrobacterium treatment this amount was 1.6, 2.2 and 9.6 fold compared with the control. All of the results indicated the positive effect of Surfactin in suppression the strain IBRC-M10701 of Agrobacterium. The results indicated the key role of Surfactin in biocontrol which reflected the possible use of Bacillus strains producing Surfactin in biological control.

ERBB2 is a member of the human epidermal growth factor receptor family and is located at large arm of chromosome 17. This receptor can activate a variety of signaling pathways which inhibit apoptosis and induce cell proliferation. MiRNAs are small, single strand, non coding RNAs that regulate gene expression at post transcriptional level and control important cellular processes such as proliferation, differentiation, apoptosis and tumor genesis. Genomic location of miRNAs demonstrated that they are located at fragile and/ or cancer related chromosomal regions. The aim of this study is production of necessary structure to over express the predicted area of a novel miRNA in ERBB2 gene following its bioinformatics prediction.

Different bioinformatics software was used to investigate stem loop structures with a potential to produce novel miRNAs, Dicer and Drosha enzymes recognition sites and conservation of interested area. Then the surrounding area of candidate stem loop structure was cloned in pEGFPC1 expression vector successfully.

Different software study shows a high probability of processing a mature miRNA. The required construct for more studies was cloned in pEGFPC1 expression vector successfully.

Bioinformatics analysis predictING stem loop structure has a potential to produce a novel miRNA.

Cancer is one of the most important factors which affect the human health. RNA interference (RNAi) based therapies have been developed and showed significant results in this regard. One of the most important problems of siRNA system is its low stability. In order to overcome to this weakness, various types of hairpin RNA or shRNA was introduced. Over expressed colorectal cancer gene (OCC-1), which has several transcripts is considered as a hallmark of colorectal cancer. This gene has vital role in the development and progression of cancer through the cell signaling pathways, which are involved in cell proliferation. In the present study, the RNAi system was utilized in order to reduce the expression of specific transcript of OCC-1 gene.
The silencer structure was designed and cloned in the expression vector pRNA-H1.1 / Neo which has a promoter for RNApolIII. Plasmid was transferred into the colorectal cancer cell line, and the expression of transcript was compared to the control samples at 24 and 72 h post transfection by Real-Time PCR.
The expression of transcript was reduced about 25 % at 72 h post transfection following shRNA transfection, compared to the control sample.
The designed shRNA structure successfully reduced the expression of target gene; accordingly, it can be used in future studies in order to investigate the effect of these transcripts on development and progression of colorectal cancer.

The cyclin E2 (CYCE2) is an important regulator in the progression and development of NSCLC, and its ectopic expression promoted the proliferation, invasion, and migration in several tumors, including Non-Small Cell Lung Cancer (NSCLC). However, the upregulation of CYCE2 in NSCLC cells suggested that it has a key role in tumorigenicity. In addition, the RAS family proteins as oncoproteins were activated in many major tumor types and its suitability as the therapeutic target in NSCLC was proposed. Considering the crucial role of microRNAs, it was hypothesized that altered expression of hsa-miR-30d-5p and hsa-let-7b might provide a reliable diagnostic tumor marker for diagnosis of NSCLC.
Real-time RT-PCR approach could evaluate the expression alteration of hsa-miR-30d-5p and hsa-let-7b and it was related to the surgically resected tissue of 24 lung cancer patients and 10 non-cancerous patients. The miRNAs expression was associated with clinicopathological features of the patients.
Hsa-miR-30d showed a significant downregulation (p=0.0382) in resected tissue of NSCLC patients compared with control group. Its expression level could differentiate different stages of malignancies from each other. The ROC curve analysis gave it an AUC=0.73 (p=0.037) which was a good score as a reliable biomarker. In contrast, hsa-let-7b was significantly overexpressed in tumor samples (p=0.03). Interestingly, our findings revealed a significant association of hsa-let-7b in adenocarcinoma tumors, compared to Squamous Cell Carcinomas (SCC) (p Together, these results suggest a possible tumor suppressor role for hsa-miR-30d in lung tumor progression and initiation. Moreover, upregulation of hsa-let-7b was associated with the tumor type.

Familial hypercholesterolemia (FH) is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B 100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population.
Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients.
A novel mutation in exon 3 (C95W) and a previously described mutation in exon 4 (D139H) of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene.
The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations.

ANRIL is an important antisense noncoding RNA gene in the INK4 locus (9p21.3), a hot spot region associated with multiple disorders including coronary artery disease (CAD), type 2 diabetes mellitus (T2DM) and many different types of cancer. It has been shown that its expression is dysregulated in a variety of immune-mediated diseases. CAD is a major problem in T2DM patients and the cause of almost 60% of deaths in these patients worldwide. The aim of the present study was to compare the expression level of ANRIL between T2DM patients with and without CAD.
In this case-control study, we examined ANRIL expression in peripheral blood mononuclear cell samples by quantitative reverse transcriptionpolymerase chain reaction (RT-qPCR) in 64 T2DM patients with and without CAD (33 CAD and 31 CADpatients respectively, established by coronary angiography).
Expression analysis revealed that ANRIL was up regulated (2.34-Fold, P=0.012) in CAD versus CAD diabetic patients. Data from receiver operating characteristic (ROC) curve analysis has shown that ANRIL could act as a potential biomarker for detecting CAD in diabetic patients.
The expression level of ANRIL is associated with presence of CAD in diabetic patients and could be considered as a potential peripheral biomarker.

The human OCT4 gene, responsible for pluripotency and self-renewal of Embryonic Stem (ES) and Embryonic Carcinoma (EC) cells, can generate several tran-scripts (OCT4A, OCT4B-variant 2, OCT4B-variant 3, OCT4B-variant 5, OCT4B1, OCT4 B2 and OCT4B3) by alternative splicing and alternative promoters. OCT4A that is responsible for ES and EC cell stemness properties is transcribed from a promoter upstream of Exon1a in those cells. The OCT4B group variants (OCT4B-variant2, OCT4B-variant3, OCT4B-variant5, OCT4B1, OCT4B2 and OCT4B3) are transcribed from a different promoter located in intron 1 and some of them respond to the cell stresses, but cannot sustain the ES/EC cell self-renewal. However, the exact function of OCT4B group variants is still unclear.
In the present study, we employed RT-PCR and sequencing approaches to explore different forms of OCT4 transcripts.
Our data revealed that the OCT4B group variants (OCT4B-variant2, OCT4 B-variant3, OCT4B1, OCT4B2 and OCT4B3) have longer 5' UTR in the human bladder carcinoma cell line of 5637.
These OCT4 variants undergo alternative splicing in their 5' UTR which might exert regulatory roles in transcription and translation mechanisms.

MiRNAs are known as regulatory genes in eukaryotic genomes, regulating their target genes expression. Here, we have investigated five pathogen responsive miRNAs; tae-miR156, tae-miR159, tae-miR167, tae-miR171 and tae-miR393 expression pattern in wheat Taichung 29 cultivar between day 10 to 20th of the seedling life. Since plant seedlings are mostly used for plant-pathogene interaction analysis, this research was committed to analyze the expression pattern of these miRNAs independent of pathogenesis and in 10 to 20 days old seedlings. Plants were grown in soil in greenhouse condition, and 10, 11, 13, 17 and 20 days old seedlings were harvested for RNA extraction and cDNA synthesis. QRT-PCR analysis of candidate miRNAs expression indicated that, tae-miR156 and tae-miR159 expression level has been sharply increased between day 13th to 17th and then after, decreased to the minimum level before day 20th. On the other hand, tae-miR167, tae-miR171 and tae-miR393 expression level has been gradually increased since day 13th of the growth. These data suggest that day 13th to 17th of the wheat seedling life, is crucial period of life in terms of drastic physiological changes which are affected by miRNAs expression. Since majority of the target genes of these candidate miRNAs are not known yet, their expression alterations is only suggested to be consistent with the expression of some known target genes, belong to the signaling pathway like auxin signaling. Considering sequence conservation pattern of miRNA precursors, here we suggested functional miR*s for tae-miR156, tae-miR159, and tae-miR393.

Umbilical cord blood is used for transplantation purposes in regenerative medicine of hematological disorders. MicroRNAs are important regulators of gene expression that control both physiological and pathological processes such as cancer development and incidence. There is a new relation between 53 (tumor suppressor gene) and miR-145 (suppressor of cell growth) upregulation. In this study, we have assessed how adipose-derived stem cells (ADSCs) affect the expansion of hematopoietic stem cells (HSCs), as well as miR-145 and p53 expressions.
In this experimental study, we cultured passage-3 isolated human ADSCs as a feeder layer. Flow cytometry analysis confirmed the presence of ADSC surface markers CD73, CD90, CD105. Ex vivo cultures of cordblood CD34 cells were cultured under the following 4 culture conditions for 7 days: i. Medium only supplemented with cytokines, ii. Culture on an ADSCs feeder layer, iii. Indirect culture on an ADSCs feeder layer (Thin Cert™ plate with a 0.4 μm pore size), and iv. Control group analyzed immediately after extraction. Real-time polymerase chain reaction (PCR) was used to determine the expressions of the p53 and miR-145 genes. Flow cytometry analysis of cells stained by annexin V and propidium iodide (PI) was performed to detect the rate of apoptosis in the expanded cells.
ADSCs tested positive for mesenchymal stem cell (MSC) markers CD105, CD90, and CD73, and negative for HSC markers CD34 and CD45. Our data demonstrated the differentiation potential of ASCs to osteoblasts by alizarin red and alkaline phosphatase staining. MTT assay results showed a higher proliferation rate of C 34燩 directly cultured on the ADSCs feeder layer group compared to the other groups. Direct contact between HSCs and the feeder layer was prevented by a microporous membrane p53 expression increased in the HSCs group with indirect contact of the feeder layer compared to direct contact of the feeder layer. p53 significantly downregulated in HSCs cultured on ADSCs, whereas miR-145 significantly upregulated in HSCs cultured on ADSCs.
ADSCs might increase HSCs proliferation and self-renewal through miR-145, 53, and their relationship.

Alternative splicing is an important mechanism that regulates gene expression and function in human cells. OCT4, a crucial pluripotency marker in embryonic stem/carcinoma cells generates several spliced variants in different cell types and cancers. The expression of OCT4 in cancers has been challenged in many studies. The existence of several OCT4 spliced variants and absence of specific discriminating primers is the main reason of this controversy. Therefore, using specific primers and discriminating OCT4 variants from each other might help to reduce these discrepancies in carcinogenesis and stem cell researches.
17 various human cancer, pluripotent and normal cells were cultured and their RNAs were extracted. Related cDNAs were synthesized and the expression pattern of OCT4 variants was investigated by RT-PCR assay. PCR products were cloned into pTZ57R/T vector and their authenticity was confirmed by DNA sequencing.
Expression pattern of OCT4 variants (OCT4A, OCT4B and OCT4B1) was analyzed by RT-PCR assay and the authenticity of PCR products was confirmed by DNA sequencing. A novel spliced variant of OCT4 was discovered and named as OCT4B3. This variant was very similar to OCT4B2 transcript except that 207-nt of exon 1b is lost. Moreover, the expression pattern of OCT4B3 variant was investigated in 17 human cell types, where its expression was only found in astrocytoma and bladder cancer cell types 1321N1 and 5637, respectively.
OCT4 variants are differentially expressed in various human cancer cell lines. Moreover, a novel variant of OCT4, OCT4B3, was detected in two human cancer cell lines of bladder carcinoma (5637) and brain astrocytoma (1321N1) for the first time.

Previous studies revealed that oxidative stress is elevated in multiple sclerosis (MS). It can harm to biological macromolecules such as DNA. However, the molecular mechanism in protection of genetic information from DNA damages is not clear in MS disease. In this study the expression level of some important genes of OGG1 and MYH involved in base excision repair pathway and, MTH1 and ITPA as main cleaning genes of nucleotide pool from rough nucleotides are examined in MS patients in compared to healthy group.
Peripheral blood mononuclear cells were isolated from relapsing-remitting-MS patients and healthy subjects. After RNA extraction and cDNA synthesis, the expression levels of target genes were examined by RT-qPCR technique.
The level of the MTH1 and MYH genes expression were decreased, but the level of OGG1 mRNA was higher in patients in comparison to the control group. Obtained result did not shown any correlation between expression of examined genes and clinical features of patients such as MS severity and disease duration.
These preliminary results provide more supportive evidences for involvement of oxidative damage and variation in expression of DNA repair genes in MS. Significant increase of OGG1 suggest that the development and progression of pathogenesis in Iranian MS can be related to chronic and direct oxidative damage of genomic DNA not nucleotide pools.

Forkhead box (FOX) proteins are important regulators of the epithelial-to-mesenchymal transition (EMT), which is the main mechanism of cancer metastasis. Different studies have shown their potential involvement in progression of cancer in different tissues such as breast, ovary and colorectum. In this study, we aimed to analyze the expression of genes encoding two FOX proteins in gastric adenocarcinoma.
In this experimental case-control study, the expression of FOXC2 and FOXQ1 was examined in 31 gastric adenocarcinoma tumors and 31 normal adjacent gastric tissues by reverse transcription polymerase chain reaction (PCR).
The expression of both genes was significantly up-regulated in gastric adenocarcinoma tumors compared with the normal tissues (P We show that up-regulation of FOXC2 and FOXQ1 are likely to be involved in the progression of gastric adenocarcinoma.

Neurotrophins are a family of secretive growth factors that do their functions via binding to their specific receptors (Trks) or their common receptor (p75ntr). p75ntr has important roles in survival, differentiation and proliferation of several types of cells. MicroRNAs are non-coding small RNAs that regulate post-transcriptional mRNA expression. Recently, a MiRNA named hsa-miR-6165 has been discovered in forth intron of p75ntr. Bioinformatics analysis has revealed that this MiRNA has important roles on regulation of several cellular signaling pathways and signaling pathway involve in differentiation. Therefore, in the present study, the expression of hsa-miR-6165 in neuronal differentiation of NT2 human embryonic carcinoma stem cell line and non-nervous and nervous human cell lines was analyzed. Our results indicated that hsa-miR-6165 not only has been expressed in differentiation process of NT2 cells and neural cell lines but although significantly expressed in several human non-neural cell lines such as hFSF and Hela. In addition, the expression of this miRNA, unlike its host gene, upregulated at the end of the differentiation. These results indicate the probable presence of independent promoter for this MiRNA and revealed that hsa-mir-6165 maybe has roles in cellular differentiation which needs more investigation.

The human OCT4 gene, the most important pluripotency marker, can generate at least three different transcripts (OCT4A, OCT4B, and OCT4B1) by alternative splicing. OCT4A is the main isoform responsible for the stemness property of embryonic stem (ES) cells. There also exist eight processed OCT4 pseudogenes in the human genome with high homology to the OCT4A, some of which are transcribed in various cancers. Recent conflicting reports on OCT4 expression in tumor cells and tissues emphasize the need to discriminate the expression of OCT4A from other variants as well as OCT4 pseudogenes.
In this experimental study, DNA sequencing confirmed the authenticity of transcripts of OCT4 pseudogenes and their expression patterns were investigated in a panel of different human cell lines by reverse transcription-polymerase chain reaction (RT-PCR).
Differential expression of OCT4 pseudogenes in various human cancer and pluripotent cell lines was observed. Moreover, the expression pattern of OCT4 pseudogene 3 (OCT4-pg3) followed that of OCT4A during neural differentiation of the pluripotent cell line of NTERA-2 (NT2). Although OCT4-pg3 was highly expressed in undifferentiated NT2 cells, its expression was rapidly down-regulated upon induction of neural differentiation.Analysis of protein expression of OCT4A, OCT4-pg1, OCT4-pg3, and OCT4-pg4 by Western blotting indicated that OCT4 pseudogenes cannot produce stable proteins. Consistent with a newly proposed competitive role of pseudogene microRNA docking sites, we detected miR-145 binding sites on all transcripts of OCT4 and OCT4 pseudogenes.
Our study suggests a potential coding-independent function for OCT4 pseudogenes during differentiation or tumorigenesis.

B> Podophyllotoxin (PTOX), a natural compound in numerous plants, contains remarkable biological properties that include anti-tumor, anti-viral such as anti-human immunodeficiency virus (HIV) activities. In order to avoid its adverse effects, various compounds have been derived from PTOX. 6-methoxy PTOX (MPTOX) is one of the natural PTOX derivatives with an extra methoxy group. MPTOX is mostly isolated from the Linum species. This study has sought to determine the biological effects of MPTOX on cancer cell lines, 5637 and K562. In this experimental study, we treated the 5637 and K562 cancer cell lines with MPTOX in a dose- and time-dependent manner. Apoptosis was examined by flow cytometry and viability rate was analyzed by the MTT assay. Expressions of the tubulin (TUBB3) and topoisomerase II (TOPIIA) genes were determined by real-time polymerase chain reaction (PCR). Treatment with MPTOX led to significant induction of apoptosis in cancer cells compared to control cells. Gene expression analysis showed reduced levels of TUBB3 and TOPIIA mRNA following MPTOX treatment. MPTOX inhibited TUBB3 and TOPIIA gene expression and subsequently induced cell death through apoptosis. These results suggested that MPTOX could be considered a potential anti-tumor agent.

A pure nucleotide pool is an essential precursor of correct DNA replication and prevention of mutagenesis and abnormality in a living cell. Inosine triphosphatase (ITPase) is a critical enzyme to remove any deaminated rough purine nucleotides such as inosine from nucleotide pool. It has been shown that the rate of substitution mutation in genomic DNA increase by abnormal function and expression of ITPA gene. The object of this study was comparisons the ITPA gene expression between human adenocarcinoma tumor with the normal margins tissues. the expression of ITPA gene was examined in 24 pairs of gastric adenocarcinoma tumor and their normal adjacent tissues using quantitative Real-Time PCR technique. the analysis gene expression showed reduction in tumor tissue in comparison with their adjacent normal tissues. The reduction in ITPA gene expression is especially significant in higher grade samples. with regard to the biological function of ITPA gene in omitting the rough deaminated purines from the nucleotides pool, it seems that lower expression of this gene can be considered as a risk factor for development and progression of gastric cancer. Also abnormality in this gene increase the frequency of mutation in genomic DNA and make a suitable background for higher genomic instability.

Although more than 98% of the human genome is transcribed, most of these transcripts are not translated into proteins. Rather, they are considered as non-coding RNAs. MicroRNAs (miRNAs) are very short non-coding RNAs approximately 22 nucleotides in length which regulate many key processes of cells such as growth, proliferation, differentiation, cell cycle, apoptosis (programmed cell death) and metabolism. On the other hand, it is known that these small regulatory molecules are involved in many human diseases such as different cancers and cardiovascular disorders. Therefore, discovery and functional characterization of novel miRNAs is a primary achievement. Low abundance and spatiotemporal expression of these mediator molecules make their discovery difficult by conventional methods. Therefore, bioinformatics software has been designed for the prediction of stem-loop structures capable of producing miRNA precursors in the human genome. On the other hand, there are several bioinformatics tools for prediction of miRNA target genes. Prediction of miRNA target genes helps to characterize the function of the miRNA. In this paper, we have reviewed some of the common efficient bioinformatics tools and experimental approaches used for prediction and identification of the miRNA genes and their target genes.

Chemotherapy has been used for centuries in cancer therapy. Different compounds and drugs are used in chemotherapy; each is applied for a specific type of cancer. Among them; plant compounds including lignans، have been used in medicine for a long time. Podophyllutoxin is a member of lignans family that is mostly extracted from Podophyllum species. It has multiple biological properties such as antiviral، antifungal and anticancer properties. Considering anticancer property of podophyllutoxin، it is used in Wilm`s tumor and genital tumors treatment. Also، it has been shown that podophyllutoxin causes apoptosis in ovary carcinoma cell line (Hela). There is not yet any report of the effect of podophyllutoxin on bladder carcinoma cell line such as 5637. In this study، we have evaluated the effect of podophyllutoxin on cell viability and apoptosis of 5637 cell line، and we have shown that podophyllutoxin causes apoptosis and death of these cells. It seems that podophyllutoxin can be an active agent to induce apoptosis of cancer cells.

Human hematopoietic stem cells (hHSCs) have been used for transplantation in hematologic failures. Because the number of hHSCs per cord blood unit is limited, the expansion of these cells is important for clinical application. It has been reported that cytokines and feeder layer provide a perspective to in vitro expansion of hHSCs. In this regard, cord blood CD34+ cells expanded after co-culture with adipose-derived stem cells (ADSCs) feeder layer and cytokine conditions were analyzed in terms of apoptosis and the expression level of p53, a tumor suppressor gene. Three cultures of cord blood CD34+ cells were prepared ex-vivo for 7 days, including cytokines stem cell factor (SCF), thrombopoietin (TPO), and fetal liver tyrosine kinase 3 ligand (Flt3L) with ADSCs feeder layer, cytokines without feeder layer, and a culture on micro porous membrane with cytokines. Apoptosis rate and the expression level of P53 gene in all groups were analyzed by real-time PCR. The data showed that p53 expression and apoptosis rate in CD34+ fresh cells were higher than other culture systems. P53 gene expression in the expanded cells at both cytokine cultures with and without ADSCs feeder layer decreased, but it was lower than other culture systems at co-culture system with cytokines (P < 0.05). Apoptosis rate in expanded cord blood CD34+ with feeder layer was significantly lower than the group without ADSCs feeder layer. It could be concluded that direct culture of CD34+on feeder layer ADSCs affects the expansion of HSCs.