Co-treatment of silymarin and cisplatin inhibited cell proliferation, induced apoptosis in ovarian cancer.

BACKGROUND: Ovarian cancer is one of the most lethal gynecological cancers among women worldwide. Cisplatin (Cis) is an effective chemotherapeutic agent used to treat several types of cancer. Silymarin (SLM) is an extract of medicinal plant Silybum marianum (milk thistle) with anti-inflammatory, anti-angiogenesis, antioxidant, and anticancer properties used alone or in combination with other drugs. OBJECTIVE: This study aimed to explore the effects of co-treatment with SLM and Cis on A2780 human ovarian cancer cell lines. METHODS: In this study, A2780 cells were treated with various concentrations of SLM and Cis, separately and in combination. Cell cytotoxicity, scratch, clonogenic, and flow-cytometry assays were accomplished to estimate cell viability, migration, colony formation, and apoptosis, respectively. Real-time PCR was utilized to determine the expression levels of miR-155 and miR-27a. RESULTS: SLM significantly reduced the proliferation of A2780 cells in a concentration- and time-dependent manner. Combination treatment with SLM and Cis was more potent than either single treatment in reducing viability, suppressing migration, inhibiting colony formation, and promoting the induction of apoptosis. Additionally, gene expression analysis revealed a significant decline in the expression levels of miR-155 and miR-27a in response to all separate and combined treatments, and co-treatment was more effective than individual treatments in altering miRNAs expression. CONCLUSION: Based on our findings, SLM boosts the anticancer activity of Cis and mitigates its side effects. Thus, the co-treatment of SLM and Cis can be proposed as a promising therapeutic strategy for further investigation.

Synergistic effects of miR-143 with miR-99a inhibited cell proliferation and induced apoptosis in breast cancer.

Breast cancer (BC) is the most common cancer type and the fifth leading cause of cancer-related deaths. The primary goals of BC treatment are to remove the tumor and prevent metastasis. Despite advances in BC treatment, more effective therapies are required. miRNAs can regulate many targets involved in biological processes and tumor progression; these molecules have emerged as a promising cancer treatment strategy. In the present study, we investigated the effects of miR-99a and miR-143 in single expression plasmids for BC inhibition. In this study, the precursor structure of miRNAs in the expression vector pEGFP-N1 entered single and double states, and MCF7 and T47D cells were transfected. The miRNAs expression level after transfection was then measured using qPCR. The MultiMiR package was used to obtain predicted and validated miRNA targets. MTT assay, qRT-PCR, migration test, and flow cytometry were used to assess the effect of miRNA and gene modulation. The qPCR results revealed that miRNA constructs were significantly expressed after the transfection of both cell lines. The biological function of miRNAs showed that upregulation of miR-99a and miR-143 in any of the two selected BC cells inhibited their proliferation and migration rate, significantly inducing apoptosis (p < 0.01). Also, miR-99a/miR-143 co-treatment has a synergistic anticancer effect in cancer cells via Akt1 and CDK6 targeting. These findings suggest that miR-99a/miR-143 plays synergistic regulatory roles in BC, possibly via a shared signaling pathway, providing a therapeutic strategy for BC treatment.

Bioinformatics analysis of a disease-specific lncRNA-miRNA-mRNA regulatory network in recurrent spontaneous abortion (RSA).

BACKGROUND: This study investigated the molecular mechanisms of long non-coding RNAs (lncRNAs) in RSA using the lncRNA-miRNA-mRNA regulatory network. METHODS: The present study obtained expression datasets of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), and microRNAs (miRNAs) from blood samples of individuals with unexplained recurrent spontaneous abortion (RSA) and healthy controls. Differentially expressed lncRNAs (DELs), mRNAs (DEMs), and miRNAs (DEmiRs) were identified. A regulatory network comprising lncRNA, miRNA, and mRNA was constructed, and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEM. Also, a protein-protein interaction (PPI) network was made and key genes were identified. RESULTS: A total of 57 DELs, 212 DEmiRs, and 301 DEMs regarding RSA were identified. Later analysis revealed a lncRNA-miRNA-mRNA network comprising nine lncRNAs, 14 miRNAs, and 65 mRNAs. Then, the ceRNA network genes were subjected to functional enrichment and pathway analysis, which showed their association with various processes, such as cortisol and thyroid hormone synthesis and secretion, human cytomegalovirus infection, and parathyroid hormone synthesis. In addition, ten hub genes (ITGB3, GNAI2, GNAS, SRC, PLEC, CDC42, RHOA, RAC1, CTNND1, and FN1) were identified based on the PPI network results. CONCLUSION: In summary, the outcomes of our study provided some data regarding the alteration genes involved in RSA pathogenic mechanism via the lncRNA-miRNA-mRNA network and reveal the possibility of identifying new lncRNAs and miRNAs as promising molecular biomarkers.

Study of quercetin and fisetin synergistic effect on breast cancer and potentially involved signaling pathways.

Naturally-derived drugs have drawn much attention in recent decades. Efficiency, lower toxicity, and economic reasons are some of their advantages that justify this broad range of administration for different diseases, including cancer. If we can find a specific combination that boosts the effects of their single therapy, leading to synergism effect, increased efficiency, and decreased toxicity, they can act even better. Quercetin and fisetin, two well-known flavonoids, have been used to fight against various cancers. In this study, we investigated their possible synergism quercetin and fisetin on MCF7, MDA-MB-231, BT549, T47D, and 4T1 breast cancer cell lines. Then the optimum combined dose was used to study their impacts on wound healing abilities and clonogenic properties. The real-time qPCR was used to study the expression of their validated downstream effectors in predicted pathways. A significant synergism effect (p < .01, combination index: <1) was observed for all cell lines. Combination therapy was significantly more effective in colony formation (p < .0001) and wound healing assays (p < .001) compared to single therapies. The expression level of potential effectors was also showed a greater change. In vivo study confirmed the in vitro results and showed how significantly (p < .001) their synergism promotes their singular function in inhibiting cancer progression. The breast cancer mouse models receiving combined therapy lived longer with higher average body weight and smaller tumor sizes. These results exhibit that quercetin and fisetin inhibit cancer cell proliferation, migration and colony formation synergistically, and matrix metalloproteinase signaling and apoptotic pathways are relatively responsible for inhibitory activities.

Naringenin in combination with quercetin/fisetin shows synergistic anti-proliferative and migration reduction effects in breast cancer cell lines.

INTRODUCTION & AIM: Breast cancer is one of the most common cancers with a high mortality rate among women worldwide. Quercetin/fisetin and naringenin, three well-known flavonoids, have been used to fight against various cancers. The aim of the present study was to investigate the possible synergism of quercetin/fisetin with naringenin on MCF7 and MDA-MB-231 breast cancer cell lines. METHODS: In this study, cultured MCF7 and MDA-MB-231 cells were treated with different concentrations of quercetin/fisetin individually and in combination with naringenin. MTT assay and scratch assay was employed to determine cell viability and migration respectively. Real-time PCR was used to study the expression level of apoptosis genes and miR-1275 (tumor suppressor miRNA) and mir-27a-3p (oncogenic miRNA). RESULTS: A synergism effect of quercetin/fisetin and naringenin (CI < 1) was observed for both cell lines. Combination therapies were significantly more effective in cell growth reduction, migration suppression and apoptosis induction than single therapies. Gene expression analysis revealed the upregulation of miR-1275 and downregulation miR-27a-3p. CONCLUSION: Our results indicate that quercetin/fisetin enhances the anti-proliferative and anti-migratory activities in combination with naringenin in MCF7 and MDA-MB-231 human breast cancer cell lines. Therefore, the combination of Que/Fis and Nar can be proposed as a promising therapeutic strategy for further investigations.

The association between genetic variation rs2292832 and the processing efficiency of pre-mir-149 affects the risk of breast cancer.

BACKGROUND: microRNAs (miRNAs) play key roles in regulating cancer development, including breast cancer. Variation in miRNA genes can associate with the risk of cancer by alterations in the miRNA's processing and maturation. Therefore, human blood samples and breast cancer cell line (MCF7) were analyzed to study any possible association between the genetic variant (rs2292832) in the miR-149 precursor and breast cancer susceptibility. METHODS: To study the role of rs2292832 polymorphism in breast cancer, the miR-149 gene variant was genotyped using PCR-RFLP. For evaluating the effect of SNP on function and expression levels of mature miR-149, we inserted pre-miR-149 and flanking region with CC or TT genotype into a pEGFPN1 expression vector, and qPCR was accomplished. Cell survival, proliferation, and migration properties investigated by MTT and wound healing assay. Statistical analysis was carried out for data analysis. RESULTS: T allele in variant rs2292832 is associated with an increased risk of breast cancer. Such association was also obtained in co-dominant (OR = 2.5) and dominant (OR = 2.016) models. The variant allele led to reduced production of mature miR-149 and resulted in increased cell proliferation and migration of MCF7 cells. CONCLUSION: These findings suggest that miR-149 suppresses tumor cell proliferation, and the pre-mir-149 polymorphism affects the processing of miR-149, causing an alteration in the abundance of the miRNA mature form, which can regulate tumor progression and metastasis.

miRNAs, oxidative stress, and cancer: A comprehensive and updated review.

Oxidative stress refers to elevated levels of intracellular reactive oxygen species (ROS). ROS homeostasis functions as a signaling pathway for normal cell survival and appropriate cell signaling. Chronic inflammation induced by imbalanced levels of ROS contributes to many diseases and different types of cancer. ROS can alter the expression of oncogenes and tumor suppressor genes through epigenetic modifications, transcription factors, and non-coding RNAs. MicroRNAs (miRNAs) are small non-coding RNAs that play a key role in most biological pathways. Each miRNA regulates hundreds of target genes by inhibiting protein translation and/or promoting messenger RNA degradation. In normal conditions, miRNAs play a physiological role in cell proliferation, differentiation, and apoptosis. However, different factors that can dysregulate cell signaling and cellular homeostasis can also affect miRNA expression. The alteration of miRNA expression can work against disturbing factors or mediate their effects. Oxidative stress is one of these factors. Considering the complex interplay between ROS level and miRNA regulation and both of these with cancer development, we review the role of miRNAs in cancer, focusing on their function in oxidative stress.

Downregulation of miR-4443 and miR-5195-3p in ovarian cancer tissue contributes to metastasis and tumorigenesis.

BACKGROUND AND PURPOSE: Ovarian cancer (OC) is one of the most fatal malignancies in women. High mortality rate may be due to problems with diagnosis in the early stages. The use of new biomarkers for faster diagnosis and selection of more efficient therapies is one of the main concerns in this area. miRNAs are non-coding and conserved molecules that are involved in regulating gene expression throughout different cell processes. Few studies have been conducted on the effects of miR-4443 and miR-5195-3p in cancer. Therefore, to determine the role of these miRNAs in OC, this study was directed to investigate the expression rate in OC tissue samples and its relationship with clinical factors. METHODS: Expression levels of miR-4443 and miR-5195 were evaluated in 45 ovarian tumor and 45 ovarian non-tumor tissue samples paraffin embedded using qPCR. Expression was investigated by miRNA-specific primers and then statistical analysis was performed to determine the significance. In the next step, the relationship between clinopathologic factors and miRNA expression was investigated. RESULTS: The results showed that miR-4443 decreased in OC in metastatic and serous OC samples (0.154-fold, P < 0.0001). As well as, significant reduction in miR-5195-3p was observed in cancer samples (0.373-fold, P < 0.0001) and its reduction was associated with metastasis. CONCLUSION: As a result, the two studied miRNAs may contribute to suppressing tumor, so that decrease in their expression is associated with increased cell proliferation and invasion. Further investigation can help to suggest these miRNAs as diagnostic biomarkers or therapeutic targets in OC.

Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation.

Polycystic ovary syndrome (PCOS) is an endocrinopathy in reproductive-age women believed to be affected by several genetics and environmental factors or both. Different miRNAs are one of such genetic factors that their associations with PCOS have been implicated. For instance, miR-146a that is well known for strongly regulating the immune response and inflammation was upregulated in serum plasma, follicular fluid and granulosa cells of PCOS patients. Different studies have shown that genetic changes in pre-miRNA can cause change in the expression or biological function of mature miRNA. Therefore, the main aim of this study was to investigate the association of miR-146a gene variation (rs2910164) with the susceptibility to PCOS. This study consists of 180 patients with PCOS and 192 healthy women matched by age and geographical region. Genotyping were determined by using PCR-RFLP in all subjects. The genotype frequency and allele distributions of all subjects were evaluated using Fisher's exact test directed by SPSS v.20. The genotype and allele frequencies of the miR-146a polymorphism (rs2910164) significantly differ between PCOS and healthy controls. The frequencies of CC genotype (p = .054) and 'C' allele (p = .0001) of the miR-146a variant indicated a significant incidence in cases compared to controls. Such association was obtained in co-dominant (OR = 3.16) and dominant (OR = 2.29) models. Result of this study can be proposed that women with miR-146a variation are at a higher risk for developing PCOS, which can be due to up-regulation of miR-146a.

High-throughput bioaccumulation, biotransformation, and production of silver and selenium nanoparticles using genetically engineered Pichia pastoris.

A genetically modified Pichia pastoris strain overexpressing a metal-resistant variant of cytochrome b5 reductase enzyme was developed for silver and selenium biosorption and for nanoparticle production. The maximum recombinant enzyme expression level was approximately 31 IU/ml in the intercellular fluid after 24 h of incubation, and the capacity of the recombinant biomass for the biosorption of silver and selenium in aqueous batch models were measured as 163.90 and 63.71 mg/g, respectively. The ions were reduced in the presence of enzyme, leading to the formation of stable 70-180 nm metal nanoparticles. Various instrumental analyses confirmed the well-dispersed and crystalline nature of the spherical nanometals. The purified silver and selenium nanoparticles exhibited at least 10-fold less cytotoxicity toward HDF, EPG85-257, and T47D cells than silver nitrate and selenium dioxide. These results revealed that the engineered Pichia strain is an eco-friendly, rapid, high-throughput, and versatile reduction system for nanometal production.

cag Pathogenicity island-dependent upregulation of matrix metalloproteinase-7 in infected patients with Helicobacter pylori.

Helicobacter pylori (H. pylori) infection has been involved in the pathogenesis of most important gastroduodenal diseases. Matrix metalloproteinases (MMPs) are a large family of zincendopeptidases which play important roles in degradation of extracellular matrix (ECM) and various inflammatory diseases. Therefore, we examined MMP-7 mRNA levels in the gastric mucosa of patients with H. pylori infection and evaluated the effects of virulence factors, such as vacA (vacuolating cytotoxin A) and cagA (cytotoxin-associated gene), in H. pylori-infected patients upon the MMP-7 mRNA mucosal levels. We also determined the correlation between mucosal MMP-7 mRNA levels and the types of disease. Total RNA was extracted from gastric biopsies of 50 H. pylori-infected patients and 50 uninfected individuals. Mucosal MMP-7 mRNA expression level in H. pylori-infected and non-infected gastric biopsies was determined by real-time polymerase chain reaction (PCR). The presences of cagA and vacA virulence factors was evaluated using PCR. MMP-7 expression was significantly higher in biopsies of patients infected with H .pylori compared to uninfected individuals. In addition, mucosal MMP-7 mRNA expression in H. pylori-infected patients significantly associated with the cagA status and the types of disease. Our results suggest that MMP-7 might be involved in the pathogenesis of H. pylori. Peptic ulcer was associated with cag pathogenicity island-dependent MMP-7 upregulation.

A glance into the roles of microRNAs (exosomal and non-exosomal) in polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The clinical symptoms include hyperandrogenism, chronic anovulation, and multiple ovarian cysts. PCOS is strongly associated with obesity and insulin resistance. MicroRNAs (miRNAs) are a group of short non-coding RNAs that play a role in the post-transcriptional regulation of gene expression and translational inhibition. They play a vital role in the regulation of multiple metabolic and hormonal processes as well as in oocyte maturation and folliculogenesis in the female reproductive system. miRNAs can be used as diagnostic biomarkers or therapeutic targets because of their stability. The encapsulation of miRNAs in extracellular vesicles or exosomes contributes to their stability. Exosomes are constantly secreted by many cells and size of about 30 to 150 nm. Enveloping miRNAs exosomes can release them for cellular communication. The induced transfer of miRNAs by exosomes is a novel process of genetic exchange between cells. Many studies have shown that along with non-exosomal miRNAs, different types of exosomal miRNAs derived from the serum and follicular fluid can play an essential role in PCOS pathogenesis. These miRNAs are involved in follicular development and various functions in granulosa cells, apoptosis, cell proliferation, and follicular atresia. The present study aimed to comprehensively review the evidence on miRNAs and their affected pathways under both non-exosomal and exosomal circumstances, primarily focusing on the pathogenesis of PCOS.

Association of hsa-miR-5571-5p Expression with Clinicopathological Factors besides Identification of Its Hub Target Genes and Key Pathway in Breast Cancer.

Background: miRNAs are small non-coding RNAs; regulate gene expression using RNA degradation or translation repression. Dysregulation of miRNAs is involved in the initiation and progression of many cancers. We aimed to determine the relationship between miR-5571-5p expression and clinical factors and regulatory mechanisms in breast cancer. Methods: Histopathologic sections approximately with 25 microns thick from FFPE tissues were achievement of Al-Zahra Hospital (Isfahan, Iran) in 2020-2021 years by Pathologist. miR-5571-5p expression, determined using real-time PCR. For miRNA target genes prediction, integrated miRNA target prediction tools, were used. Gene ontology and KEGG pathway analysis were accomplished to identify the biological function. A PPI network was constructed to display key target genes. For hub genes validation, GEPIA databases were used. Results: miR-5571-5p was upregulated in breast tumor tissues, and its increase was significantly related to a poor prognosis in breast cancer (P<0.0001). At first, 324 target genes were predicted, and then 110 genes with a decrease in expression were selected. GO analysis showed that genes were mainly enriched in the regulation of the ERBB2 and EGFR signaling pathway. KEGG pathway analysis suggested that downregulated genes were enriched in glioma, the ErbB signaling pathway, and breast cancer. Finally, the ten hub genes (EGF, PIK3R1, SOS1, PTEN, SHC1, CBLB, LIFR, LEP, PDE1C, and NT5C2) were detected from the PPI network. Conclusion: miR-5571-5p up-regulation is associated with breast cancer progression and worse survival. The current study identified ten genes associated with breast cancer, which might help to provide candidate targets for the treatment.

Co-Delivery of Silymarin and Metformin Dual-Loaded in Mesoporous Silica Nanoparticles Synergistically Sensitizes Breast Cancer Cell Line to Mitoxantrone Chemotherapy.

The development nano-carriers based therapeutic methods is a potent strategy for enhancing cellular delivery of drugs and therapeutic efficiency in cancer chemotherapy. In the study, silymarin(SLM) and metformin (Met) were co-loaded into mesoporous silica nanoparticles (MSNs) and evaluated the synergistic inhibitory effect of these natural herbal compound in improving chemotherapeutic efficiency against MCF7MX and MCF7 human breast cancer cells. Nanoparticles have been synthesized and characterized by FTIR, BET, TEM, SEM, and X-ray diffraction. Drug loading capacity and release determined. The both single and combined form of SLM and Met (free and loaded MSN) were used for MTT assay, colony formation and real time-PCR in cellular study. The synthesis MSN were uniformity in size and shape with particle size of approximately 100 nm and pore size of approximately 2 nm. The Met-MSNs IC30, SLM -MSNs IC50 and dual-drug loaded MSNs IC50 were much lower than of free-Met IC30, free-SLM IC50 and free Met-SLM IC50 MCF7MX and MCF7cells. The co-loaded MSNs treated cells were increased sensitivity to mitoxantrone with the inhibition of BCRP mRNA expressions and could induce apoptosis in MCF7MX and MCF7 cells in comparison with other groups. Colony numbers were significantly reduced in comparison to with other groups in the co-loaded MSNs -treated cells ( ). Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human breast cancer cells. The findings of the present study suggest that the anti-cancer effects of both metformin and silymarin enhances against breast cancer cells when MSNs are used as a drug delivery system.

Novel polymorphism rs12402181 in the mature sequence of hsa-miR-3117-3p has a protective effect against breast cancer development by affecting miRNA processing and function.

The current study aimed to investigate how the rs12402181 variant in the miR-3117-3p seed region affects miRNA processing and binding ability to the target sequences and breast cancer susceptibility. To study the role of rs12402181 polymorphism in breast cancer, blood samples were examined to investigate the possible association between the genetic variant in the miR-3117 and breast cancer susceptibility. The miR-3117 gene variant was genotyped using PCR-RFLP. The pre-miR-3117 and parts of the flanking region with GG or AA genotype were inserted into a pEGFPN1 expression vector and followed by qPCR to evaluate the effect of SNP on miR-3117-3p expression levels and function. Cell proliferation and migration properties investigated by MTT and wound healing assay. Web server databases were used for further investigation of potential changes in miRNA function. Genotype frequency study in breast cancer patients and healthy controls showed that rs12402181 polymorphism (G > A) is inversely associated with susceptibility to breast cancer (P = 0.03, OR 0.551). The variant allele led to increased production of mature miR-3117 and reduced cell proliferation and migration in MCF7 and T47D cells. These findings suggest that A allele in miR-3117-3p affects the processing of miRNA, causing an increase in the miRNA mature form which can negatively regulate tumor development and migration. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03765-y.

Mechanism and function of miR-140 in human cancers: A review and in silico study.

MicroRNA-140 (miR-140) acts as a tumor suppressor and plays a vital role in cell biological functions such as cell proliferation, apoptosis, and DNA repair. The expression of this miRNA has been shown to be considerably decreased in cancer tissues and cell lines compared with normal adjacent tissues. Consequently, aberrant expression of some miR-140 target genes can lead to the initiation and progression of various human cancers, such as breast cancer, gastrointestinal cancers, lung cancer, and prostate cancer. The dysregulation of the miR-140 network also affects cell proliferation, invasion, metastasis, and apoptosis of cancer cells by affecting various signaling pathways. Besides, up-regulation of miR-140 could enhance the efficacy of chemotherapeutic agents in different cancer. We aimed to cover most aspects of miR-140 function in cancer development and address its importance in different stages of cancer progression.

Bioengineered chimeric tRNA/pre-miRNAs as prodrugs in cancer therapy.

Today, biologic prodrugs have led to targeting specific tumor markers and have increased specificity and selectivity in cancer therapy. Various studies have shown the role of ncRNAs in cancer pathology and tumorigenesis and have suggested that ncRNAs, especially miRNAs, are valuable molecules in understanding cancer biology and therapeutic processes. Most miRNAs-based research and treatment are limited to chemically synthesized miRNAs. Synthetic alterations in these miRNA mimics may affect their folding, safety profile, and even biological activity. However, despite synthetic miRNA mimics produced by automated systems, various carriers could be used to achieve efficient production of bioengineered miRNAs through economical microbial fermentation. These bioengineered miRNAs as biological prodrugs could provide a new approach for safe therapeutic methods and drug production. In this regard, bioengineered chimeric miRNAs could be selectively processed to mature miRNAs in different types of cancer cells by targeting the desired gene and regulating cancer progression. In this article, we aim to review bioengineered miRNAs and their use in cancer therapy, as well as offering advances in this area, including the use of chimeric tRNA/pre-miRNAs.

Glycyrrhizic acid enhances the anticancer activity of cisplatin in the human ovarian cancer cell line.

This study aimed to investigate the effects of glycyrrhizic acid (GL) on the anticancer activity of cisplatin in A2780 ovarian cancer cells. Cultured A2780 cells were treated with different concentrations of GL and cisplatin individually and in combination. The MTT assay, flow cytometry, wound-healing, and clonogenic assay, were used to determine cell viability, apoptosis, migration, and colony formation, respectively. The effects on superoxide dismutase (SOD) activity were also evaluated. QPCR was used to study the effects of individual and combined treatments with GL and cisplatin on the expression levels of migration genes (MMP2 and MMP9), and some apoptosis pathway genes (caspase-3, -8, -9, and BCL2). A synergistic effect was observed between GL and cisplatin (CI < 1). Combination therapy was significantly more effective in reducing cell viability, suppressing migration and colony formation, inducing apoptosis, and altering gene expression compared to single therapies. GL significantly increased SOD activity. The relative expression of caspase -3, -8, and - 9 increased significantly, and the expression levels of MMP2 and MMP9 decreased significantly in the treated cells. Our results indicate that GL enhances the anticancer activity of cisplatin in the A2780 cell line. Therefore, the combination of GL and cisplatin can be proposed as a promising therapeutic strategy for ovarian cancer.

Contribution of hsa-miR-146a and hsa-miR-223 gene variations in patients with multiple sclerosis reveals association of rs2910164 and rs1044165 with risk of multiple sclerosis susceptibility.

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as candidate biomarkers. Single-nucleotide polymorphisms (SNPs) in miRNA genes can be related to the risk of different autoimmune diseases. Some of these SNPs are rs2910164 in the miR-146a and rs1044165 in the miR-223. The aim of this study was to investigate the relationship between these polymorphisms and the risk of multiple sclerosis (MS) in an Iranian population. In this case-control study, 261 patients with MS and 250 healthy controls that matched by age and geographical region were enrolled. After sampling and genomic DNA extraction, genotyping was determined by PCR-restriction fragment length polymorphism. Allelic and genotypic associations between the SNPs and MS were evaluated by the data analysis conducted by SPSS V.20. The frequencies of rs2910164 and rs1044165 SNPs were significantly different between the patients with MS and healthy controls. C and T alleles in the variants rs2910164 and rs1044165, respectively, are associated with increased risk of MS. Such association was obtained in codominant, dominant, and overdominant models for both variants (OR ~3 and OR ~1.5, respectively). Furthermore, this study determined that the C and T alleles of rs2910164 and rs1044165 are risk factors for MS in the Iranian population.

Regulatory and immunomodulatory role of miR-34a in T cell immunity.

miRNAs are a class of non-coding RNAs and very conserve molecules that negatively regulate the expression of many genes by targeting the 3' UTR of mRNAs. miRNAs are involved in the modulation of T-cell biology during the earliest and last stages and key controllers of T-cell differentiation and function. The miR-34a, as a major hub of the regulatory network of T cells, plays an important role in T cell activation. miR-34a is widely expressed in immune cells (dendritic cells, macrophages, mast cells, B cells, and T cells) and regulates their development, function, and survival. This miRNA, by targeting over 30 genes across different cellular pathways controls immune response. miR-34a expression is controlled by p53 in transcription level. As well as, miR-34a by activating dendritic cells mediates innate immune response and increases tumor-infiltrating CD8 expression T lymphocytes. In various types of cancers and autoimmune diseases, miR-34a can regulate T cell function and become a possible significant target of microRNA-based therapy. Therefore, in this review, we focus on miR-34a-related regulatory mechanisms in T cell function and understanding mechanisms and molecules involved in this network.