Identification and validation of miR-583 and mir-877-5p as biomarkers in patients with breast cancer: an integrated experimental and bioinformatics research.

OBJECTIVES: Breast cancer (BC) is one of the most common cancers with a high mortality rate in women worldwide. The advantages of early cancer diagnosis are apparent, and it is a critical factor in increasing the patient's life and survival. According to mounting evidence, microRNAs (miRNAs) may be crucial regulators of critical biological processes. miRNA dysregulation has been linked to the beginning and progression of various human malignancies, including BC, and can operate as tumor suppressors or oncomiRs. This study aimed to identify novel miRNA biomarkers in BC tissues and non-tumor adjacent tissues of patients with BC. Microarray datasets GSE15852 and GSE42568 for differentially expressed genes (DEGs) and GSE45666, GSE57897, and GSE40525 for differentially expressed miRNAs (DEMs) retrieved from the Gene Expression Omnibus (GEO) database were analyzed using "R" software. A protein-protein interaction (PPI) network was created to identify the hub genes. MirNet, miRTarBase, and MirPathDB databases were used to predict DEMs targeted genes. Functional enrichment analysis was used to demonstrate the topmost classifications of molecular pathways. The prognostic capability of selected DEMs was evaluated through a Kaplan-Meier plot. Moreover, the specificity and sensitivity of detected miRNAs to discriminate BC from adjacent controls were assessed by area under the curve (AUC) using the ROC curve analysis. In the last phase of this study, gene expression on 100 BC tissues and 100 healthy adjacent tissues were analyzed and calculated by using the Real-Time PCR method. RESULTS: This study declared that miR-583 and miR-877-5p were downregulated in tumor samples in comparison to adjacent non-tumor samples (|logFC|< 0 and P ≤ 0.05). Accordingly, ROC curve analysis demonstrated the biomarker potential of miR-877-5p (AUC = 0.63) and miR-583 (AUC = 0.69). Our results showed that has-miR-583 and has-miR-877-5p could be potential biomarkers in BC.

The Importance of mir-491-5p in Various Cancers.

MicroRNAs are non-coding ribonucleic acids that are evolutionarily protected. MiRNAs control the expression of genes after transcription by mRNA decomposition or the inhibition of their translation. These molecular structures control physiological and pathological processes; therefore, many of them can play vital roles as oncogenes or tumor inhibitors. Besides, the occurrence of various mutations in miRNAs can lead to cancer. In this review article, we want to peruse the role of miR-491-5p in various cancers. In recent years, many experiments and studies have been performed on the involvement of miR-491-5p in cancer, invasion, and cell metastasis. Metastasis is an event that makes cancer more advanced and harder to treat. When cancer is invasive, the cancer cells invade nearby tissues or other organs and develop cancer. Tumor studies have shown that miR-491-5p can inhibit cell growth, invasion, and metastasis. Thus, expression enhancement of miR-491-5p disrupts cell migration and improves cancer.

The role of miRNA-424 and miR-631 in various cancers: Focusing on drug resistance and sensitivity.

BACKGROUND: However, advanced technologies have been developed in the treatment of various cancers, but the mortality rate from cancer is still very high. Drug resistance is a major problem for patients with cancer, which causes the treatment process to fail. In addition to inhibiting drug resistance, targeted therapy is also very important in treatment. MAIN BODY: Nowadays, miRNAs have gained increasing interest as they play a major role in both drug resistance and targeted therapy. MicroRNA (miRNA) is an important part of non-coding RNA that regulates gene expression at a post-transcriptional level. The prevailing studies about miRNA expression have been expanded into a variety of neoplasms. MiR-424 and miR-631 targets genes involved in various cellular processes and can participate in proliferation, differentiation, apoptosis, invasion, angiogenesis, and drug resistance and sensitivity. CONCLUSION: In this study, we focus on the role of miR-424 and miR-631 in many cancer types by displaying the potential target genes associated with each cancer, as well as briefly describing the clinical uses of miR-424 and miR-631 as a diagnostic and predictive tool in malignancies.

Circular RNAs as novel biomarkers in triple-negative breast cancer: a systematic review.

More effective prognostic and diagnostic tools are urgently required for early detecting and treating triple-negative breast cancer, which is the most acute type of breast cancer because of its lower survival rate, aggressiveness, and non-response to various common treatments. So, it remains the most harmful malignancy for women worldwide. Recently, circular RNAs, as a group of non-coding RNAs, with covalently closed loop and high stability have been discovered, which can modulate gene expression through competing with endogenous microRNA sponges. This finding provided further insight into novel approaches for controlling genes affected in many disorders and malignancies. This review concentrates on the dysregulated expression of circRNAs like their diagnostic and prognostic values in TNBC. This review aims to focus on the abnormal expression of circRNAs and their diagnostic and prognostic values in TNBC. We used PubMed, Embase, and Web of Science databases and ClinicalTrials.gov to systematically search for all relevant clinical studies. This review is based on articles published in databases up to April 2022 with the following keywords: "Circular RNA", "CircRNA", "Triple-Negative Breast Cancer" and "TNBC". We conducted a review of published CircRNA profiled-research articles to identify candidate CircRNA biomarkers for TNBC. The review is registered on JBI at https://jbi.global/systematic-review-register . Accumulating evidence has shown that several circRNAs are downregulated and some are upregulated in TNBC. The results of these studies confirm that circRNAs might be potential biomarkers with the diagnostic, prognostic, and therapeutic target value for TNBC. We also consider the connection between circRNAs and TNBC cell proliferation, apoptosis, metastasis, and chemotherapy resistance and sensitivity.

The contributing factors of resistance or sensitivity to epigenetic drugs in the treatment of AML.

Drug resistance is the drug-effectiveness reduction in treatment and is a serious problem in oncology and infections. In oncology, drug resistance is a complicated process resulting from enhancing the function of a pump that transports drugs out of tumor cells, or acquiring mutations in drug target. Surprisingly, most drugs are very effective in the early stages, but the response to the drug wears off over time and resistance eventually develops. Drug resistance is caused by genetic and epigenetic changes that affect cancer cells and the tumor environment. The study of inherited changes in the phenotype without changes in the DNA sequence is called epigenetics. Because of reversible changes in epigenetics, they are an attractive target for therapy. Some of these epigenetic drugs are effective in treating cancers like acute myeloid leukemia (AML), which is characterized by the accumulation and proliferation of immature hematopoietic cells in the blood and bone marrow. In this article, we outlined the various contributing factors involved in resistance or sensitivity to epigenetic drugs in the treatment of AML.

Escherichia coli and Colorectal Cancer: Unfolding the Enigmatic Relationship.

Colorectal cancer (CRC) is one of the deadliest cancers in the world. Specific strains of intestinal Escherichia coli (E. coli) may influence the initiation and development of CRC by exploiting virulence factors and inflammatory pathways. Mucosa-associated E. coli strains are more prevalent in CRC biopsies in comparison to healthy controls. Moreover, these strains can survive and replicate within macrophages and induce a pro-inflammatory response. Chronic exposure to inflammatory mediators can lead to increased cell proliferation and cancer. Production of colobactin toxin by the majority of mucosa-associated E. coli isolated from CRC patients is another notable finding. Colibactin-producing E. coli strains, in particular, induce double-strand DNA breaks, stop the cell cycle, involve in chromosomal rearrangements of mammalian cells and are implicated in carcinogenic effects in animal models. Moreover, some enteropathogenic E. coli (EPEC) strains are able to survive and replicate in colon cells as chronic intracellular pathogens and may promote susceptibility to CRC by downregulation of DNA Mismatch Repair (MMR) proteins. In this review, we discuss current evidence and focus on the mechanisms by which E. coli can influence the development of CRC.

CASP5 and CR1 as potential biomarkers for Kawasaki disease: an Integrated Bioinformatics-Experimental Study.

BACKGROUND: Kawasaki disease (KD) is a pediatric inflammatory disorder causes coronary artery complications. The disease overlapping manifestations with a set of symptomatically like diseases such as bacterial and viral infections, juvenile idiopathic arthritis, Henoch-Schönlein purpura, infection of unknown etiology, group-A streptococcal and adenoviral infections, and incomplete KD could lead to misdiagnosis of the disease. METHODS: In the present study, we applied weighted gene co-expression network analysis (WGCNA) to identify network modules of co-expressed genes in GSE73464 and also, limma package was used to identify the differentially expressed genes (DEGs) in KD expression arrays composed of GSE73464, GSE18606, GSE109351, and GSE68004. By merging the results of WGCNA and limma, we detected hub genes. Then, analyzed the peripheral blood mononuclear cells (PBMCs) of 16 patients and 8 control subjects using Real-Time Polymerase Chain Reaction (RT-PCR) to evaluate the previous results. RESULTS: We assessed the diagnostic potency of the screened genes by plotting the area under curve (AUC). We finally identified 2 genes CASP5(Caspase 5) and CR1(Complement C3b/C4b Receptor 1) which were shown to potentially discriminate KD from other similar diseases and also from healthy people. CONCLUSIONS: The results of RT-PCR and AUC confirmed the diagnostic potentials of two suggested biomarkers for KD.

Integrative analysis of DNA methylation and gene expression profiles to identify biomarkers of glioblastoma.

Glioblastoma multiforme (GBM) is the most common, most invasive, and malignant type of primary brain tumor with poor prognosis and poor survival rate. Using GSE22891 the expression and methylation status of same GBM patients was evaluated to identify key epigenetic genes in GBM. Using |log2FC| > 1 and FDR 〈 0.05 as the threshold, DEGs including 4910 downregulated and 2478 upregulated were screened and by |log2FC| 〉 0.2 and p-value < 0.05, 3223 DMCs were detected. By merging the results of DEGs and DMCs, 643 genes were selected for network analysis by WGCNA, and based on expression values three modules and by methylation values, one module was selected. Using STRING and Cytoscape databases, PPI network of genes of all modules were constructed separately. According to the PPI network, core genes were picked out. The expression status of core genes was evaluated using GSE77043, GSE42656, GSE30563, GSE22891, GSE15824, and GSE122498, and 50 genes were validated. The methylation status of 50 genes was explored using GSE50923, GSE22891, and GSE36245, and finally, 12 hub genes including ARHGEF7, RAB11FIP4, PPP1R16B, OLFM1, CLDN10, BCAT1, C1QB, C1QC, IFI16, NUP37, PARP9, and PCLAF were selected. Using GEPIA database, the expression and by cBioportal the survival plot and also scatterplot of methylation versus expression of 12 hub genes were extracted based on TCGA. To determine the diagnostic values of the hub genes, the receiver operating characteristic (ROC) curve and the area under the curve (AUC) were extracted based on GSE22891 and GSE122498. Finally, we evaluated the expression level of the genes in tissue of 83 GBM patients and also non-tumoral adjacent (as control) tissues.

Laboratory methods to decipher epigenetic signatures: a comparative review.

Epigenetics refers to nucleotide sequence-independent events, and heritable changes, including DNA methylation and histone modification (as the two main processes), contributing to the phenotypic features of the cell. Both genetics and epigenetics contribute to determining the outcome of regulatory gene expression systems. Indeed, the flexibility of epigenetic effects and stability of genetic coding lead to gene regulation complexity in response signals. Since some epigenetic changes are significant in abnormalities such as cancers and neurodegenerative diseases, the initial changes, dynamic and reversible properties, and diagnostic potential of epigenomic phenomena are subject to epigenome-wide association studies (EWAS) for therapeutic aims. Based on recent studies, methodological developments are necessary to improve epigenetic research. As a result, several methods have been developed to explore epigenetic alterations at low, medium, and high scales, focusing on DNA methylation and histone modification detection. In this research field, bisulfite-, enzyme sensitivity- and antibody specificity-based techniques are used for DNA methylation, whereas histone modifications are gained based on antibody recognition. This review provides a mechanism-based understanding and comparative overview of the most common techniques for detecting the status of epigenetic effects, including DNA methylation and histone modifications, for applicable approaches from low- to high-throughput scales.

Investigation the Cytotoxicity of 5-AZA on Acute Lymphoblastic Leukemia Cell Line In Vitro and Characterization the Underlying Molecular Mechanisms of Cell Death and Motility.

DNA methylation is a reversible biochemical process determinant of gene expression that is frequently observed in acute lymphoblastic leukemia (ALL). This is believed to arise from aberrant DNA methyltransferase activity establishing abnormal levels of DNA methylation in tumor cells. DNA methyltransferase inhibitor, 5-azacytidine (5-AZA), is a clinically used epigenetic drug which induces promoter demethylation and gene re-expression in human cancers. In this study, we investigated the cytotoxicity of on MOLT4 and Jurkat leukemic cell line in vitro and characterized the underlying molecular mechanisms of cell death and motility. MOLT4 and Jurkat cells were treated with 5-AZA for 12, 24 and 48 hours. The effect of the 5-AZA treatment on cell viability (MTT assay), apoptosis (annexin V/PI staining), microRNA (miRNA) and mRNA expression (real-time PCR) was measured. The results showed that 5-AZA could induce MOLT4 and Jurkat apoptotic cell death in vitro in a time-dependent manner and probably via apoptotic mechanisms. We found that treatment with 5-AZA could increase the expression of epigenetically silenced miRNAs, miR-34a, miR-34b and miR-124-1 in treated cells. In addition, mRNA analyses demonstrated that MOLT4 and jurkat cells, expressed p53 gene more than 10-fold higher compared with untreated cells in three independent experiments while the cells suppressed the expression of a subset of functionally related genes including MYC, BCL2, APEX, SIRT1, SNAIL1 and vimentin to some extent, following 5-AZA treatment. We found that a miRNAs expression level in treated cell lines was closely correlated to the expression of their target genes. Together, these findings suggest that 5-AZA may affect the viability of MOLT4 and jurkat cells, at least in part, by regulating the transcription of genes that are associated with cellular apoptotic response.

Mucosa-Associated Escherichia coli in Colorectal Cancer Patients and Control Subjects: Variations in the Prevalence and Attributing Features.

Accumulating evidence indicates that specific strains of mucosa-associated Escherichia coli (E. coli) can influence the development of colorectal carcinoma. This study aimed to investigate the prevalence and characterization of mucosa-associated E. coli obtained from the colorectal cancer (CRC) patients and control group. At two referral university-affiliated hospitals in northwest Iran, 100 patients, 50 with CRC and 50 without, were studied over the course of a year. Fresh biopsy specimens were used to identify mucosa-associated E. coli isolates after dithiothreitol mucolysis. To classify the E. coli strains, ten colonies per sample were typed using enterobacterial repetitive intergenic consensus-based PCR (ERIC-PCR). The strains were classified into phylogroups using the quadruplex PCR method. The PCR method was used to examine for the presence of cyclomodulin, bfp, stx1, stx2, and eae-encoding genes. The strains were tested for biofilm formation using the microtiter plate assay. CRC patients had more mucosa-associated E. coli than the control group (p < 0.05). Enteropathogenic Escherichia coli (EPEC) was also found in 23% of CRC strains and 7.1% of control strains (p < 0.05). Phylogroup A was predominant in control group specimens, while E. coli isolates from CRC patients belonged most frequently to phylogroups D and B2. Furthermore, the frequency of cyclomodulin-encoding genes in the CRC patients was significantly higher than the control group. Around 36.9% of E. coli strains from CRC samples were able to form biofilms, compared to 16.6% E. coli strains from the control group (p < 0.05). Noticeably, cyclomodulin-positive strains were more likely to form biofilm in comparison to cyclomodulin-negative strains (p < 0.05). In conclusion, mucosa-associated E. coli especially cyclomodulin-positive isolates from B2 and D phylogroups possessing biofilm-producing capacity colonize the gut mucosa of CRC patients.

CircRNAs as potent biomarkers in ovarian cancer: a systematic scoping review.

More powerful prognostic and diagnostic tools are urgently needed for identifying and treating ovarian cancer (OC), which is the most fatal malignancy in women in developed countries. Circular RNAs (circRNAs) are conservative and stable looped molecules that can regulate gene expression by competing with other endogenous microRNA sponges. This discovery provided new insight into novel methods for regulating genes that are involved in many disorders and cancers. This review focuses on the dysregulated expression of circRNAs as well as their diagnostic and prognostic values in OC. We found that studies have identified twenty-one downregulated circRNAs and fifty-seven upregulated ones. The results of these studies confirm that circRNAs might be potent biomarkers with diagnostic, prognostic and therapeutic target value for OC. We also consider the connection between circRNAs and OC cell proliferation, apoptosis, metastasis, and chemotherapy resistance and sensitivity.

CML derived exosomes promote tumor favorable functional performance in T cells.

BACKGROUND: Leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. There are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. We explained here that K562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of human primary cord blood-derived T cells (CB T cells). METHODS: Human primary cord blood-derived T cells were treated with K562-derived exosomes. We evaluated the expression variation of some critical genes activated in suppressor T cells. The alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using ELISA assay and real-time PCR. Finally, NO production and intracellular ROS level in CB T cells were evaluated using Greiss assay and flow cytometry, respectively. RESULTS: Our results showed the over-expression of the genes involved in inhibitory T cells, including NQO1, PD1, and FoxP3. In contrast, genes involved in T cell activation such as CD3d and NFATc3 have been reduced significantly. Also, the expression of interleukin 10 (IL-10) and interleukin 6 (IL-6) mRNAs were significantly up-regulated in these cells upon exosome treatment. In addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (IL-17) proteins increased in T cells exposed to K562-derived exosomes. Finally, K562-derived exosomes induce significant changes in the NO production and intracellular ROS levels in CB T cells. CONCLUSIONS: These results demonstrate that K562-derived exosomes stimulate the immunosuppressive properties in CB-derived T cells by inducing anti-inflammatory cytokines such as IL-10, reducting ROS levels, and arising of NO synthesis in these cells. Moreover, considering the elevation of FOXP3, IL-6, and IL-17 levels in these cells, exosomes secreted by CML cells may induce the fates of T cells toward tumor favorable T cells instead of conventional activated T cells.

The related miRNAs involved in doxorubicin resistance or sensitivity of various cancers: an update.

Doxorubicin (DOX) is an effective chemotherapy agent against a wide variety of tumors. However, intrinsic or acquired resistance diminishes the sensitivity of cancer cells to DOX, which leads to a cancer relapse and treatment failure. Resolutions to this challenge includes identification of the molecular pathways underlying DOX sensitivity/resistance and the development of innovative techniques to boost DOX sensitivity. DOX is classified as a Topoisomerase II poison, which is cytotoxic to rapidly dividing tumor cells. Molecular mechanisms responsible for DOX resistance include effective DNA repair and resumption of cell proliferation, deregulated development of cancer stem cell and epithelial to mesenchymal transition, and modulation of programmed cell death. MicroRNAs (miRNAs) have been shown to potentiate the reversal of DOX resistance as they have gene-specific regulatory functions in DOX-responsive molecular pathways. Identifying the dysregulation patterns of miRNAs for specific tumors following treatment with DOX facilitates the development of novel combination therapies, such as nanoparticles harboring miRNA or miRNA inhibitors to eventually prevent DOX-induced chemoresistance. In this article, we summarize recent findings on the role of miRNAs underlying DOX sensitivity/resistance molecular pathways. Also, we provide latest strategies for utilizing deregulated miRNA patterns as biomarkers or miRNAs as tools to overcome chemoresistance and enhance patient's response to DOX treatment.

The expression of miR-513c and miR-3163 was downregulated in tumor tissues compared with normal adjacent tissue of patients with breast cancer.

BACKGROUND: Breast cancer (BC) is the most invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered critical nutrition that many cancer cells, particularly BC cells, are dependent on it for growth and proliferation. Therefore, targeting glutamine metabolism, especially enzymes that are related to this pathway, can be beneficial to design anti-cancer agents. Recent evidence has shown that microRNAs (miRNAs), with a short length and single-strand properties, play a prominent role in regulating the genes related to glutamine metabolism, which may control the development of cancer. METHODS: In silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism. The expression level of these two miRNAs was evaluated in eighty BC tissues and normal adjacent tissues. Furthermore, GSE38167, GSE38867, GSE42128, GSE45666, and GSE53179 were employed from gene expression omnibus (GEO). The Limma package was utilized to identify differentially expressed miRNAs (DEMs) of mentioned datasets to evaluate miR-513c and miR-3163 expression. Further, in silico analysis was utilized to predict the potential biological processes and molecular pathways of miR-513c and miR-3163, based on their target genes. RESULTS: In silico studies revealed top categories of biological processes and cellular pathways that might play a critical role in metabolism reprogramming and cancer development and were target genes for miR-513c and miR-3163. The current study showed that miR-513c (p value = 0.02062 and FC = - 2.3801) and miR-3163 (p value = 0.02034 and FC = - 2.3792) were downregulated in tumor tissues compared to normal adjacent tissues. The analysis of GEO microarray datasets showed that miR-513c was downregulated in GSE38167, GSE38867, GSE42128, GSE45666 and GSE53179, whereas there was a significant downregulation of miR-3163 in only two studies, including GSE38867 and GSE42128 that they were in accordance with our experimental results. Furthermore, the subgroup analysis did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history of cancer, and abortion history. CONCLUSION: MiR-513c and miR-3163 were downregulated in BC tissues, which might serve as tumor suppressors. They are suggested as potential therapeutic targets for patients with BC.

The pathways related to glutamine metabolism, glutamine inhibitors and their implication for improving the efficiency of chemotherapy in triple-negative breast cancer.

Breast cancer (BC) is a heterogeneous cancer with multiple subtypes affecting women worldwide. Triple-negative breast cancer (TNBC) is a prominent subtype of BC with poor prognosis and an aggressive phenotype. Recent understanding of metabolic reprogramming supports its role in the growth of cancer cells and their adaptation to their microenvironment. The Warburg effect is characterized by the shift from oxidative to reductive metabolism and external secretion of lactate. The Warburg effect prevents the use of the required pyruvate in the tricarboxylic acid (TCA) cycle progressing through pyruvate dehydrogenase inactivation. Therefore, it is a major regulatory mechanism to promote glycolysis and disrupt the TCA cycle. Glutamine (Gln) can supply the complementary energy for cancer cells. Additionally, it is the main substrate to support bioenergetics and biosynthetic activities in cancer cells and plays a vital role in a wide array of other processes such as ferroptosis. Thus, the switching of glucose to Gln in the TCA cycle toward reductive Gln metabolism is carried out by hypoxia-inducible factors (HIFs) conducted through the Warburg effect. The literature suggests that the addiction of TNBC to Gln could facilitate the proliferation and invasiveness of these cancers. Thus, Gln metabolism inhibitors, such as CB-839, could be applied to manage the carcinogenic properties of TNBC. Such inhibitors, along with conventional chemotherapy agents, can potentially improve the efficiency and efficacy of TNBC treatment. In this review, we discuss the associations between glucose and Gln metabolism and control of cancer cell growth from the perspective that Gln metabolism inhibitors could improve the current chemotherapy drug effects.

Effect of Mimic Hypoxia on the Proliferation and Expression of miR-27a, miR-9, miR-370 and their Target Genes in MOLT-4 and KG1a Cell Lines.

OBJECTIVE: The aim of this study was to investigate the effect of mimic hypoxia on proliferation, the expression of significant miRNAs, and genes involved in drug resistance in MOLT-4 and KG1 cell lines. MATERIALS AND METHODS: The KG1 and MOLT-4 cell lines were cultured in RPMI 1640 medium supplemented with 20% FBS and 10% FBS respectively. The MTT test was used for determining  the optimum dose of CoCl2 for KG1 and MOLT-4 cell lines. Western blotting was used for the detection of HIF-1a protein and the confirmation of mimic hypoxia induced by CoCl2. For evaluating the effect of mimic hypoxia on proliferation of MOLT-4 and KG1 cell lines, cell counting was done using trypan blue at 24, 48, and 72 hours. Furthermore, the results obtained from cell counting were confirmed with the MTT test. Total RNA was extracted  using the RNX Plus solution kit according to the manufacturer's protocol. The expression of genes and miRNAs was evaluated with real time PCR. RESULTS: According to this study, mimic hypoxia induced by CoCl2 contributes to the overexpression of drug resistance related genes including MDR1, MRP1, FOXM1, BCL-xl genes, and the suppression of PUMA gene compared to the control group. The results also showed that mimic hypoxia condition leads to the up-regulation of miR-9 and down-regulation of miR-27a and miR-370. Additionally, our outcomes demonstrated that mimic hypoxia has an inhibitory effect on the proliferation of MOLT-4 and KG1 cell lines. CONCLUSION: Treatment with CoCl2 has an inhibitory effect on the proliferation of MOLT-4 and KG1 cell lines independent from real hypoxia. Additionally, mimic hypoxia has a substantial effect on the expression of  genes and miRNAs involved in drug resistance. Finally, we are still far away to discover the exact functional mechanisms of hypoxia on drug resistance but these evaluations can provide new perspectives into this field for the upcoming studies.

The expression of miRNA-152-3p and miRNA-185 in tumor tissues versus margin tissues of patients with chemo-treated breast cancer.

OBJECTIVE: Breast cancer (BC) is the most significant and lethal type of cancer in women. Although there are many newly develop chemotherapy drugs for patients with BC treating at various stages, drug resistance is the most important obstacle in their effectiveness for BC treatment. On the other hand, microRNAs are considered key regulators of genes involved in carcinogenesis and chemoresistance in cancers. The purpose of this study was to evaluate the role of miR-152-3p and miR-185 in intrinsic chemoresistance and proliferation of BC. In addition, the potential role of these miRNAs during chemoresistance was evaluated through possible signaling pathways. RESULTS: Here, miR-152-3p was significantly downregulated in tumor tissues compared to the corresponding margin tissues in patients with BC (p-value ≥ 0.04407 and fold change = - 2.0552). In contrast, no statistically significant difference was observed in the miR-185 expression between the two groups. Furthermore, no significant correlation was found between the expression of these two miRNAs and subfactors, including cancer family history, abortion, and age. Downregulation of miR-152-3p could be considered a promising regulator of BC chemoresistance.

Overview of host miRNA properties and their association with epigenetics, long non-coding RNAs, and Xeno-infectious factors.

MicroRNA-derived structures play impressive roles in various biological processes. So dysregulation of miRNAs can lead to different human diseases. Recent studies have extended our comprehension of the control of miRNA function and features. Here, we overview some remarkable miRNA properties that have potential implications for the miRNA functions, including different variants of a miRNA called isomiRs, miRNA arm selection/arm switching, and the effect of these factors on miRNA target selection. Besides, we review some aspects of miRNA interactions such as the interaction between epigenetics and miRNA (different miRNAs and their related processing enzymes are epigenetically regulated by multiple DNA methylation enzymes. moreover, DNA methylation could be controlled by diverse mechanisms related to miRNAs), direct and indirect crosstalk between miRNA and lnc (Long Non-Coding) RNAs as a further approach to conduct intercellular regulation called "competing endogenous RNA" (ceRNA) that is involved in the pathogenesis of different diseases, and the interaction of miRNA activities and some Xeno-infectious (virus/bacteria/parasite) factors, which result in modulation of the pathogenesis of infections. This review provides some related studies to a better understanding of miRNA involvement mechanisms and overcoming the complexity of related diseases that may be applicable and useful to prognostic, diagnostic, therapeutic purposes and personalized medicine in the future.