Immune Features of Tumor Microenvironment: A Genetic Spotlight.

A tumor represents a highly intricate tissue entity, characterized by an exceptionally complex microenvironment that starkly contrasts with the typical physiological surroundings of healthy tissues. Within this tumor microenvironment (TME), every component and factor assume paramount importance in the progression of malignancy and exerts a pivotal influence on a patient's clinical outcome. One of the remarkable aspects of the TME is its remarkable heterogeneity, not only across different types of cancers but even within the same histological category of tumors. In-depth research has illuminated the intricate interplay between specific immune cells and molecules and the dynamic characteristics of the TME. Recent investigations have yielded compelling evidence that several mutations harbored by tumor cells possess the capacity to instigate substantial alterations in the TME. These mutations, often acting as drivers of tumorigenesis, can orchestrate a cascade of events that remodel the TME, thereby influencing crucial aspects of cancer behavior, including its invasiveness, immune evasion, and response to therapies. It is within this nuanced context that the present study endeavors to provide a concise yet comprehensive summary of how specific mutations, within the genetic landscape of cancer cells, can instigate profound changes in TME features. By elucidating the intricate relationship between genetic mutations and the TME, this research aims to contribute to a deeper understanding of cancer biology. Ultimately, the knowledge gained from this study holds the potential to inform the development of more targeted and effective treatments, thereby offering new hope to patients grappling with the complexities of cancer.

Evaluation of Expression Levels of NFATc2 and PPARG Genes Two Effector Elements of WNT Pathway in Non-Small Cell Lung Carcinoma.

Background: There is an emergency need in discovering an efficient profile of molecular biomarkers for early diagnosis of Non-small cell lung cancer (NSCLC). Transcription factors as important groups of regulators that are able to adjust the cell cycles have attracted the attention of most researchers recently. NFATc2 and PPARG are two important factors that have been selected for this project to assess their potential for being a biomarker for NSCLC. Materials and Methods: Here in this study, 50 NSCLC patients were included. During bronchoscopy, which was their routine diagnostic approach, we collected tumoral and marginal normal tissues. After the extraction of the total RNA from the tissues, cDNA was synthesized, and the transcriptional level of NFATc2 and PPARG was examined by quantitative real-time PCR. Subsequently, the data were analyzed by proper statistical analyses. Results: The mRNA expression of NFATc2 and PPARG were down-regulated in biopsy tissues of NSCLC patients compared with their pair marginal tissues (Pvalues were 0.0011 and <0.0001 respectively). Moreover, both of them had significant AUC (area under the curve) in the ROC curve analysis (0.65 for NFATc2 and 0.81 for PPARG, Pvalue <0.05). Conclusion: It appears that mRNA expression of NFATc2 and PPARG possesses the potential to be regarded as a diagnostic or prognostic biomarker for NSCLC.

Association of the Toll-like receptor 4 and NOX4 gene and protein levels in asthmatic patients with metabolic syndrome: A case-control study.

Background: Understanding the contributing of influence inflammatory biomarkers in asthmatic patients with metabolic syndrome is more important. Whereby, the present study considering the important association of NADPH oxidase4 (NOX4) and Toll- like receptor4 (TLR4) in the respiratory inflammatory responses in asthmatic patients with metabolic syndrome (AS-MetS) and asthmatic (AS) patients. Materials and Methods: In this case-control study, 30 AS and 34 AS-MetS patients were enrolled. The Peripheral blood mononuclear cells (PBMCs) mRNA and protein levels of TLR4 and NOX4 were measured by qRT-PCR and western blot, respectively. Then their correlation was evaluated. Results: The significant down-regulation of mRNA and protein PBMCs expression levels of TLR4 were observed in the AS-MetS group in comparison to AS one (P=0.03), but the NOX4 expression was non-significant. Additionally, the significant correlation was exhibited between mRNA expression levels of NOX4 and TLR4 in both AS-MetS (r= 0.440, P=0.009) and AS groups (r=0.909, P=0.0001). The association between TLR4 mRNA level and triglyceride in AS-MetS group (r=0.454, P=0.008,) and also white blood cells (WBC) in AS group (r= -0.507, P=0.006,) were significant. Conclusion: The metabolic syndrome can significantly influence the expressions of TLR4 in AS-MetS. This study indicated that TLR4 and NOX4 altogether may provide valuable molecular knowledge of their relation with metabolic syndrome criteria for finding major pathways in different phenotype of asthma.

Sex-specific association of exposure to air pollutants and Nrf2 gene expression and inflammatory biomarkers in exhaled breath of healthy adolescents.

Studies investigating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels in the respiratory system of healthy subjects are scarce. Moreover, separate studies on the health-related outcomes of air pollution for each sex are limited. The current panel study investigated sex-specific Nrf2 expression levels and related oxidative stress and inflammatory responses among healthy adolescents exposed to PM2.5, PM10, O3, and PM2.5-bounded metals in a high traffic region. Forty-nine healthy nonsmoking subjects participated in the study for five consecutive months (Nov. 2019 to Feb. 2020). Each subject was asked to provide 1 mL of exhaled breath condensate (EBC). Data were analyzed using linear mixed-effects models. The results showed that PM10, PM2.5, O3, and PM2.5-bounded metals were negatively linked to Nrf2 expression level in EBC of females with -58.3% (95% CI: 79.5, -15.4), -32.1% (95% CI: -50.3, -7.1), -76.2% (95% CI: -92.6, -23.9), and -1.9 (95% CI: -3.4, -0.4), respectively. While our results presented no significant association between the studied pollutants and Nrf2 gene expression in males, significant associations were observed between the pollutants and total nitric oxide (NOx), interleukins 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the EBC of females. In the case of males, only EBC cytokines showed a significant association with air pollutants. Overall, this study suggests that exposure to ambient air pollutants may affect the respiratory system with biologically different mechanisms in males and females. PM2.5 concentration had a positive correlation with exhaled TNF-α and IL6 values in females while positive correlation with TNF-α and negative correlation with IL6 values in males. O3 had a negative correlation with TNF-α in males.

MicroRNA-Based Biomarkers in Lung Cancer: Recent Advances and Potential Applications.

INTRODUCTION: MicroRNAs (miRNAs) are a group of small noncoding RNAs (ncRNAs) that post-transcriptionally control the expression of genes by binding and degrading their target mRNAs. miRNAs can function as possible tumor suppressors or oncogenes in various cancers. Lately, miRNAs application as a biomarker (prognosis and diagnosis) for different diseases has gained much attention. miRNAs exist in a stable form in several biological materials, including tissue, plasma, and serum. The noninvasive and easy screening of miRNAs in serum, blood, tissue, and other body fluids and acceptable stability make microRNA a noticeable factor as biomarkers in human malignancies. MATERIALS AND METHODS: In this review, we searched some online databases like Web of Science, Embase, and PubMed to find eligible manuscripts up to the end of 2021. RESULTS: Abnormal expressions of these molecules are associated with the incidence of many illnesses like cancer. Therefore, they are candidates as a molecular tool for noninvasive tumor prognosis and diagnosis. In the current study, we introduce important miRNAs that may be used as prognostic and diagnostic markers in lung cancer patients. CONCLUSION: We summarized the latest reports about critical miRNAs related to the diagnosis and prognosis in lung patients.

Novel diagnostic potential of miR-1 in patients with acute heart failure.

BACKGROUND: A number of circulating micro-ribonucleic acids (miRNAs) have been introduced as convincing predictive determinants in a variety of cardiovascular diseases. This study aimed to evaluate some miRNAs' diagnostic and prognostic value in patients with acute heart failure (AHF). METHOD: Forty-four AHF patients were randomly selected from a tertiary heart center, and 44 healthy participants were included in the control group. Plasma levels of assessed miRNAs, including miR -1, -21, -23, and -423-5-p were measured in both groups. The patients were followed for one year, and several clinical outcomes, including in-hospital mortality, one-year mortality, and the number of readmissions, were recorded. RESULTS: An overall 88 plasma samples were evaluated. There was no significant difference in terms of demographic characteristics between the AHF and healthy groups. Our findings revealed that mean levels of miR-1, -21, -23, and -423-5-p in AHF patients were significantly higher than in the control group. Although all assessed miRNAs demonstrated high diagnostic potential, the highest sensitivity (77.2%) and specificity (97.7%) is related to miR-1 for the values above 1.22 (p = 0.001, AUC = 0.841; 95%CI, 0.751 to 946). Besides, the levels of miR-21 and -23 were significantly lower in patients with ischemia-induced HF. However, the follow-up data demonstrated no significant association between miRNAs and prognostic outcomes including in-hospital mortality, one-year mortality, and the number of readmissions. CONCLUSION: The result of our study demonstrated that miR-1, -21, -23, and -423-5-p can be taken into account as diagnostic aids for AHF. Nevertheless, there was no evidence supporting the efficacy of these miRNAs as prognostic factors in our study.

Regulatory Effect of let-7f Transfection in Non-Small Cell Lung Cancer on its Candidate Target Genes.

Background: Let-7f has essential impacts on biological processes; however, its biological and molecular functions in lung cancer pathogenesis have yet been remained unclear. We aimed to investigate the expression level of let-7f and its candidate target genes both in lung cancer tissues and A549 cell line. Methods: Bioinformatics databases were first used to select candidate target genes of let-7f. Then the relative gene and protein expressions of let-7f and its target genes, including HMGA2, ARID3B, SMARCAD1, and FZD3, were measured in lung tissues of NSCLC patients and A549 cell line using qRT-PCR and Western blotting. The electroporation method was used to transfect A549 cells with let-7f mimic and microRNA inhibitor. The impact of let-7f transfection on the viability of A549 cells was assessed using MTT assay. The expression data of studied genes were analyzed statistically. Results: Results indicated significant downregulated expression level of let-7f-5p (p = 0.0013) and upregulated level of the HMGA2 and FZD3 in NSCLC cases (p < 0.05). In A549 cells, after transfection with let-7f mimic, the expression of both mRNA and protein levels of HMGA2, ARID3B, SMARCAD1, and FZD3 decreased. Also, the overexpression of let-7f significantly inhibited the A549 cell proliferation and viability (p = 0.017). Conclusion: Our findings exhibited the high value of let-7f and HMGA2 as biomarkers for NSCLC. The let-7f, as a major tumor suppressor regulatory factor via direct targeting genes (e.g. HMGA2), inhibits lung cancer cell viability and proliferation and could serve as a marker for the early diagnostic of NSCLC.

Combination Therapy with KRAS and P38α siRNA Suppresses Colorectal Cancer Growth and Development in SW480 Cell Line.

PURPOSE: Colorectal cancer (CRC) is one of the most prevalence malignancies in a different society with a high rate of death. The KRAS and p38α axes have critical roles in the development, migration, and growth of numerous tumors, such as colorectal malignancy. KRAS mutation acts as an oncogene in various cancers and is correlated with the poor prognosis in colorectal tumors. Also, p38α plays different roles and exhibits tissue-dependent activity. In some tissues act as an oncogene while in others act as a tumor suppressor. In this research, we try to understand the effect of the P38α and KRAS genes suppression by specific siRNAs on the SW480 cell line progression. METHODS: We evaluate the impact of the P38α and KRAS gene knockdown by special siRNA on the growth and development of the SW480 cell line. SW480 cell line was treated with KRAS and P38α siRNAs, and the cell viability, gene expression, migration ability, and rate of apoptosis were evaluated with MTT assay, real-time PCR, scratch test, and flow cytometry. RESULTS: After treatment of the cancer cell with KRAs and P38α siRNAs, cell viability reduced to 29.16%. Also, the expression levels of the KRAS and P38α genes reduced to 26.34% and 16.06%, respectively. Apoptosis rate after combination therapy with KRAS and P38α siRNAs increased to 72.1. Also, we found that these siRNAs suppress cell migration in SW480 cell lines. CONCLUSION: The current study showed that combination therapy with p38α and KRAS siRNA may be considered a novel therapy for colorectal tumor in future.

Significance of microRNA-330-5p/TYMS Expression Axis in the Pathogenesis of Colorectal Tumorigenesis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment. METHODS: The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. RESULTS: TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p was associated with tumor stage and lymph node metastases. CONCLUSION: The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods.

Association Between NOX4 And Nrf2 Genes in Non-Small-Cell Lung Carcinoma: A Case-Control Study.

BACKGROUND: Epithelial malignancy in lung cancer, which is initiated with myofibroblast differentiation and remodeling, promotes hypoxia and intracellular ROS generation most affected by the prototypical enzyme, NADPH oxidase 4 (NOX4). In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a critical transcription factor by stimulating antioxidant proteins as redox homeostasis regulators. The aim of this study was to investigate a possible correlation between lung tissue NOX4 and Nrf2 genes (NOX4 and Nrf2) mRNA expression and bronchoalveolar lavage fluid (BALF) protein expression in non-small-cell lung carcinoma (NSCLC) patients. METHODS: Samples from 25 patients with various NSCLC types and stages and 20 healthy controls were collected. NOX4 and Nrf2 mRNA were measured by qRT-PCR, and protein by western blot analysis. RESULTS: NOX4 mRNA and protein expression was significantly up-regulated in NSCLC patients' lung tissues and BALFs (p= 0.03 and 0.01, respectively). In addition, by adjusting for age, sex, and NSCLC types and stages, a significant and positive correlation was observed between NOX4 and Nrf2 mRNA expression (r= 0.927, p= 0.001). This was also true when not adjusted as above (r= 0.944, p< 0.001). CONCLUSION: NOX4 mRNA and protein expression is significantly up-regulated in NSCLC patients' lung tissues and BALFs, and NOX4 and Nrf2 mRNA expression is positively correlated in NSCLC tissues.

Acute responses of airway oxidative stress, inflammation, and hemodynamic markers to ambient PM2.5 and their trace metal contents among healthy adolescences: A panel study in highly polluted versus low polluted regions.

Particulate air pollutants are known contributors to global cardiorespiratory mortality through several pathways. We examined the effects of varied exposure to PM2.5 and trace metals on biological markers of airway inflammation, oxidative stress, and hemodynamic function of young individuals living in two different exposure settings. We enrolled and followed a panel of 97 healthy nonsmoking participants aged 15-18 years living in a highly polluted metropolitan city of Tabriz (TBZ) and a much less polluted semi-urban town of Hadishahr (HDS). For five consecutive months, the subjects were examined by a physician, and fractional exhaled nitric oxide levels (FENO) were measured. Samples of exhaled breath condensation (EBC) were obtained for measuring interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and total nitric oxide (NOx). We measured daily outdoor PM2.5 mass concentration in a fixed station in each location for all this period. The PM-metal content was analyzed by ICP-MS. The linear mixed-effects regression models were applied for data analysis. The averages of PM2.5 mass and total metals in TBZ were nearly two and four times higher than in HDS, respectively. In TBZ, an increased IQR of PM2.5 mass during 0-5 days was -correlated with a significant rise in diastolic blood pressure, heart rate, TNF-α, FENO, and NOx and reduction of IL-6. Moreover, exposure to low PM2.5 concentration is significantly -correlated with an elevation in diastolic blood pressure in HDS. We also observed that exposure to metal constituents in the highly polluted region is correlated with increased TNF-α and IL-6 with 131.80% (95% CI: 56.01, 244.39) and 47.51% (95% CI: 33.01, 62.05) per IQR of Hg, respectively. This study suggests that exposure to ambient PM2.5 and their metal contents in highly polluted areas may incite significant changes in airway inflammation, oxidative stress, and hemodynamic parameters in healthy subjects.

Terminalia Catappa Extract (TCE) Reduces Proliferation of Lung and Breast Cancer Cell by Modulating miR-21 and miR-34a Expressions.

BACKGROUND: After cardiovascular illness, cancer is the one of the main and second cause of death in the worldwide. Despite significant advances in this field, low survival, drug resistance, and side effects of chemotherapy remain an unsolved problem. Due to the high mortality rate among cancer patients, finding the new substance to treatment with low side effects is important. Previous studies have been informed that positive effects of herbal medicines on cancer patients, which are very efficient in the treatment of cancer. METHODS: In this study, the antitumor effect of ethanolic Terminalia catappa leaf extract (TCE) on MCF-7, MDA-231, and A549 cell lines was examined. For this reason, the effects of TCE on cell migration, gene expression, and growth were investigated by scratch, test, real-time PCR (qPCR) qPCR, and MTT tests respectively. RESULTS: As a reported by the MTT outcomes, TCE significantly decreased the viability of A549, MCF-7, and MDA-231 cells (P < 0.05).  Moreover, genes expression patterns that are related to proliferation (miR-21, miR-34a), migration (MMP-13, Vimentin), and apoptosis (Cas-3, Cas-8, Cas-9, Bcl-2, Bax) also have changed significantly after treatment with TCE. Also, in the A549 cell line, Bax (p value: 0.029), Cas-9 (p value: 0.00023), miR-34a (p value: 0.031), Bcl-2 (p value: 0.0076), MMP-13 (p value: 0.041), Cas-3 (p value: 0.00051) and in MCF-7 cell line Bax (p value: 0.0004), Cas-3 (p value: 0.0003), Cas-9(p value: 0.037), miR-34a (p value: 0.005), Bcl-2(pvalue:0.0007), mir-21(p value:0.016), MMP-13(p value: 0.011) and in MDA-231 cell line Bax(p value<0.0001), Cas-3(p value: 0.003), Cas-9(p value: 0.0004). mir-34a (p value:0.0019), Bcl-2(p value:0.0023), MMP-13(p value: 0.032) have significantly changed compare to control group. CONCLUSION: The outcomes of this research determined that T. Catappa might be a potential source of antitumor compounds and could be a candidate for further research.
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Long non-coding RNAs as potential biomarkers in the prognosis and diagnosis of lung cancer: A review and target analysis.

Long non-coding RNAs (lncRNA) have been emerged as a novel class of molecular regulators in cancer. They are dysregulated in many types of cancer; however, there is not enough knowledge available on their expression and functional profiles. Lung cancer is the leading cause of the cancer deaths worldwide. Generally, lncRNAs may be associated with lung tumor pathogenesis and they may act as biomarkers for the cancer prognosis and diagnosis. Compared to other invasive prognostic and diagnostic methods, detection of lncRNAs might be a user-friendly and noninvasive method. In this review article, we selected 27 tumor-associated lncRNAs by literature reviewing to further discussing in detail for using as diagnostic and prognostic biomarkers in lung cancer. Also, in an in silico target analysis, the "Experimentally supported functional regulation" approach of the LncTarD web tool was used to identifying the target genes and regulatory mechanisms of the selected lncRNAs. The reports on diagnostic and prognostic potential of all selected lncRNAs were discussed. However, the target genes and regulatory mechanisms of the 22 lncRNAs were identified by in silico analysis and we found the pathways that are controlled by each target group of lncRNAs. They use epigenetic mechanisms, ceRNA mechanisms, protein interaction and sponge mechanism. Also, 10, 23, 5, and 28 target genes for each of these mechanisms were identified, respectively. Finally, each group of target genes controls 50, 12, 7, and 2 molecular pathways, respectively. In conclusion, LncRNAs could be used as biomarkers in lung cancer due to their roles in control of several signaling pathways related to lung tumors. Also, it seems that lncRNAs, which use epigenetic mechanisms for modulating a large number of pathways, could be considered as important subjects for lung cancer-related diagnostic and prognostic biomarkers.

Anticancer Impacts of Terminalia catappa Extract on SW480 Colorectal Neoplasm Cell Line.

PURPOSE: Colorectal cancer (CRC) is one of the most lethal and prevalent cancers throughout the world. Despite the remarkable advance in the field, drug resistance still remains as an unresolved problem in cancer. Hence, finding effective compounds with minimal side effects to fight cancer is of central priority. Herbal products have been traditionally used to prevent and treat a variety of diseases. METHODS: In the present study, the antitumor effect of Terminalia catappa plant ethanolic extract (TCE) was assessed on SW480 CRC model cell line. In this regard, effects of TCE were evaluated on the proliferation, apoptosis, and migration of SW480 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V/PI flow cytometry, and scratch tests, respectively. Furthermore, changes in the expression of genes involved in these events including Bax, Bcl-2, Caspase 3, Caspase 8, Caspase 9, MMP-13, miR-21, and miR-34a were measured by quantitative real-time PCR (qRT-PCR). RESULTS: According to the MTT results, TCE reduced the proliferation of SW480 cells significantly. The flow cytometry test also revealed a notable rate of apoptosis induction after TCE treatment. An inhibitory effect on cell migration was also evident in scratch test. Expression patterns of the assessed genes also changed subsequent to TCE treatment. CONCLUSION: The results of this study indicated that T. catappa could be considered as a potential source of anticancer compounds and a candidate for further investigations.

Dendritic cell therapy in cancer treatment; the state-of-the-art.

Dendritic cells (DCs) are considered as professional antigen presenting cells (APCs), containing a variety of subsets, that can be resident in organs or migrating among the lymphoid and non-lymphoid organs. In a normal steady condition, DCs concomitantly process and present antigens on major histocompatibility complex (MHC) class I and II. However, they are further activated after exposing to antigens. Recently, several approaches have been exerted to improve antigen presentation potency, to elicit powerful immune responses against tumor cells. In DC-based cancer immunotherapy, DC is obtained from patient and modulated ex vivo in order to entice the immune system toward tumor elimination. Several approaches have been on the evaluation for long-term anti-tumor immune responses by DCs. On the other side, combination of DC vaccines with other cancer therapies, like chemotherapy and monoclonal antibodies could confer efficient cancer therapeutics. In this review article, we first go through the immunobiology of DC, and development of DC vaccines. Then, we concentrate on the DC immunotherapy by highlighting combinational approaches to enhance the efficacy of cancer treatment strategies.

Evaluation of the Methylation of MIR129-2 Gene in Gastric Cancer.

BACKGROUND: Genetic and epigenetic changes have strong role in the development of gastric cancer. The mutation of the MIR129-2 gene is one of the major causes in many cancers, especially gastric cancer. The aim of this study was to investigate the methylation changes of the MIR129-2 gene in tumor and normal tissue of patients with gastric cancer. METHOD: In this study, 50 gastric cancer patients with Iranian Azari ethnic origin without any familial relations were included. Genomic DNAs was extracted from the tumoral and normal tissues. Then the promotor regions of the MIR129-2 gene were analyzed by methylation-specific PCR (MSP) to evaluate the presence or absence of methylated CpG sites. RESULTS: There was a statistically significant difference in methylation level of MIR129-2 gene between tumoral and normal tissues. It was observed that 84 out of 100 CpG cites were methylated in tumoral tissues in compression to 13 out of 100 CpG cites in normal tissues. CONCLUSION: MIR129-2 gene was hypermethylated in tumoral tissues, suggesting that methylation is involved in the development of gastric cancer.

Transcript Level of MicroRNA Processing Elements in Gastric Cancer.

BACKGROUND: Aberrant expression of microRNAs (miRNAs) has been implicated in the etiopathogenesis and development of various cancers. Drosha and Dicer are the main components of the miRNA biosynthesis machine. Another enzyme, DGCR8, is the assistant of Drosha in the processing complex. Here, we tried to evaluate the mRNA transcript level of Drosha, Dicer, and DGCR8 genes in involved tissues from patients with gastric cancer. METHODS: Fifty tumoral and their marginal tissues, as the control group, were obtained from patients with gastric cancer. After RNA extraction from tissues and cDNA synthesis, quantification of mRNA expression of Drosha, Dicer, and DGCR8 was conducted using SYBR Green master mix and real-time PCR. RESULTS: It was observed that mRNA expression levels of Drosha, Dicer, and DGCR8 were significantly upregulated in tumoral tissues compared with marginal tissues. Upregulation of these genes was not correlated with clinical manifestations of the patients. CONCLUSIONS: Upregulation of Drosha, Dicer, and DGCR8 plays a role in the development of cancer, probably through dysregulated the expression level of miRNAs.

Expression Level of Caspase Genes in Colorectal Cancer

Background: Caspases proteins are protease enzymes involved in the initiation and execution of apoptosis process. Regulation of apoptosis process plays an important role in the normal biological events and development. In addition to developmental abnormalities, dysregulated apoptosis system may lead to tumorigenesis, autoimmunity, and other serious health problems. Aberrant regulation of apoptosis may also be the paramount cause of chemoresistance during cancer therapy. It is aimed through this study to evaluate the transcript levels of Caspase 3, 8, and 9 in tumoral tissues from patients with colorectal cancer (CRC) and compare it with normal marginal tissues. Methods: Fifty tumor tissues and their matched marginal tissues, as control group, were obtained from CRC patients. Total mRNA of all tissue samples was extracted and cDNA was synthesized. Using SYBR Green PCR master mix and Real-time gene expression technique, the transcript level of target genes was quantified. Results: Experiments indicated that mRNA expressions of caspase 9 and 3 were downregulated in tumoral tissues from CRC patients in comparison to marginal tissues. In contrast, tumoral tissues expressed mRNA of caspase 8 higher than normal marginal tissues. Modified transcript levels of caspase 3, 8, and 9 were correlated with the clinical manifestations of the patients. Conclusions: Alteration in the mRNA level of caspase genes may be involved in the development of CRC.

TP53 Gene Pro72Arg (rs1042522) Single Nucleotide Polymorphism as Not a Risk Factor for Colorectal Cancer in the Iranian Azari Population

Background: The p53 protein participates critically in several cellular functions such as cell growth and DNA repair. Polymorphisms in the TP53 locus have repeatedly been implicated in the pathogenesis of cancers all over the world. Over 200 single nucleotide polymorphisms (SNPs) have been characterized, but one well-known example at at codon 72, Pro72Arg (rs1042522), has the displayed inconsistent results with regard to cancer risk. Herein, we aimed to evaluate whether Pro72Arg (rs1042522) single nucleotide polymorphism (SNP) in TP53 gene might be associated with risk of colorectal cancer in the Iranian Azari population. Methods: Blood samples were taken from 100 healthy controls and 100 colorectal cancer patients with Iranian-Azeri ethnicity. Genotyping was performed with Tetra-ARMS PCR. Results: The alleles of the TP53 gene Pro72Arg SNP did not significantly differ in prevalence between patients and controls (P>0.05). Additionally, genotypes of Pro72Arg SNP were not significantly associated with colorectal cancer risk in the studied population. Conclusions: Pro72Arg SNP of TP53 gene may not be involved in the disease pathogenesis in Iranian Azari patients with colorectal cancer.

mRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors in colorectal carcinoma.

Transcription factors are involved in cell cycle and apoptosis regulation and thus have a key role in the carcinogenesis of different tumors. Nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors are important in the carcinogenesis of colorectal cancer (CRC). In this study, we examined whether the expression of NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC. A total of 47 tumor samples and matched normal tissue margins were collected during surgery from patients with CRC. In addition, three CRC cell lines (HCT119, SW480, and HT29) and healthy cell line were used. After total RNA extraction and cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real-time polymerase chain reaction. The results showed that NFATc2 is overexpressed in the tumor tissues compared with normal tissue margins (p ≤ 0.05). However, the mRNA expression levels of PPARG were not significantly different between the tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as an early diagnostic or predictive biomarker for CRC as well as a therapeutic target, providing that upcoming studies confirm these results.