ABSTRACT
In the current study, the expression levels of two important lncRNAs, i.e., AK058003 and APOC1P1, in breast tumors were compared with adjacent non-tumor tissues to evaluate their diagnostic potential in a panel of 121 patients. Total RNA was extracted, cDNA was synthesized and expression of AK058003 and APOC1P1 was assessed using qRT-PCR. A significant overexpression and positive correlation between these two lncRNAs were observed in tumor tissues compared to marginal healthy tissues. In conclusion, the examined lncRNAs were overexpressed in tumor tissues, suggesting their significant diagnostic value in breast cancer.
Subject(s)
Breast Neoplasms , RNA, Long Noncoding , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
PURPOSE: Gastric cancer (GC) is one of the most frequent tumors worldwide and identification of a sensitive and specific prognostic biomarker is of great importance. Long non-coding RNAs (lncRNAs) play crucial roles in tumorigenesis of various malignancies. In the present study, we investigated lncRNA FOXD2-AS1 expression in gastric tumors and assessed its potential as a prognostic biomarker. METHODS: A total of 95 tumor and corresponding adjacent non-tumor tissue specimens were collected from patients with GC from Imam Reza hospital, Tabriz, Iran. Total RNA was isolated and FOXD2-AS1 expression was measured using quantitative reverse transcriptase (qRT)-PCR. RESULTS: FOXD2-AS1 was significantly upregulated in tumor samples as compared to non-tumor tissues (P < 0.0001). In addition, higher expression of FOXD2-AS1 was significantly associated with lymph node metastasis and Helicobacter pylori infection. The receiver operating characteristic (ROC) curve analysis revealed that FOXD2-AS1 might be served as a potential prognostic biomarker for GC. CONCLUSION: FOXD2-AS1 is upregulated in gastric tumors and can be used as a valuable biomarker in the prognosis of patients with GC.
Subject(s)
Helicobacter Infections , Helicobacter pylori , RNA, Long Noncoding , Stomach Neoplasms , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Helicobacter Infections/complications , Helicobacter Infections/genetics , Helicobacter pylori/genetics , Humans , Prognosis , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: Novel coronavirus (SARS-CoV-2) became an epidemic disease and lead to a pneumonia outbreak first in December 2019 in Wuhan, China. The symptoms related to coronavirus disease-19 (COVID-19) were different ranging from mild to severe lung injury and multi-organ failure symptoms, eventually leading to death, especially in older patients with other co-morbidities. The receptor of this virus in the human cell is angiotensin-converting enzyme 2 (ACE2). METHODS: In this paper, we aimed to perform an in silico analysis of the frequently studied variants of the ACE2 gene and determine the effects of the variants in mRNA secondary structure and binding affinity of cellular factors. Fourteen single-nucleotide polymorphisms were selected based on previous studies and investigated. RESULTS: All of the variants were analyzed in the RNAsnp database and three revealed a significant p-value. The spliceAid2 database prediction showed that 7 out of 14 SNPs caused an alteration in a way that only the wild or mutated form was able to bind to proteins. The latter database also reported that three SNPs produces a dual form in which different specific proteins can bind to the sequence in a specific form (either wild or mutated form). CONCLUSION: Altogether, these estimations revealed the potential of variants in manipulation of the final stable form of ACE2 that can lead to different COVID-19 susceptibility.
Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Computational Biology/methods , Polymorphism, Single Nucleotide , RNA, Messenger/chemistry , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , Computer Simulation , Genetic Predisposition to Disease , Humans , Models, Molecular , Nucleic Acid Conformation , RNA, Messenger/metabolismABSTRACT
BACKGROUND: Cancer stem cells (CSCs) are a small subpopulation of cells within tumors and play significant roles in tumorigenesis, metastasis, resistance to treatment, and relapse. They are defined by self-renewal and multi-lineage differentiation, and aggressiveness. Epigenetic modifications, including DNA methylation and acetylation, histone modifications, and non-coding. RNAs (ncRNAs), are partly responsible for CSC potentials and are involved in the modification of key components of crucial pathways such as Notch and Wnt signaling in breast cancer. OBJECTIVE: In this review, we present an overview of the pathways and epigenetic events that lead to the transformation of mammary gland stem cells to breast CSCs (BCSCs). Based on the data presented here, important pathways such as TGF-ß/SMAD2 and Wnt/ß-catenin and epigenetic modifications, including histone modifications, DNA methylations, and microRNAs, play important roles in BCSC formation and maintenance. CONCLUSION: Epigenetic events can alter the expression of genes and functional RNAs, resulting in tumor initiation and progression. Thus, a better understanding of epigenetic modifications involved in BCSC maintenance signaling pathways may help to eliminate or suppress BCSCs and overcome cancer by generating more effective and efficient therapeutic agents.
Subject(s)
Breast Neoplasms , Epigenesis, Genetic , Neoplastic Stem Cells , Breast Neoplasms/genetics , Female , Humans , Mammary Glands, Human/cytology , Neoplasm Recurrence, Local , Signal TransductionABSTRACT
BACKGROUND: The Notch signaling pathway has a key role in angiogenesis and Delta - Like Ligand 4 (DLL4) is one of the main ligands of Notch involved in cell proliferation in sprouting vessels. OBJECTIVE: In this study, we aimed to evaluate the expression of DLL4 in primary breast tumors and to examine the effect of melatonin on DLL4 expression in vitro. METHODS: Eighty-five breast tumor and paired adjacent non-tumor tissue samples were collected. Apoptosis assay was performed on breast cancer cells to evaluate melatonin effects. Western blot and quantitative RT-PCR were used to measure DLL4 expression. Then, we investigated the effect of melatonin on the expression of DLL4 in four breast cancer cell lines at RNA and protein levels. We also performed a probabilistic neural network analysis to study genes closely associated with DLL4 expression. RESULTS: Our results showed a significantly higher expression of DLL4 in tumor tissues compared to non-tumor tissues (P = 0.027). Melatonin treatment substantially attenuated DLL4 expression in BT474 and MCF-7 cells, but not in SK-BR-3 and MDA-MB-231 cells. Also, melatonin induced apoptosis in all four cell lines. Network analysis revealed a set of 15 genes that had close association and interaction with DLL4. DLL4 was overexpressed in breast cancer tissues as compared to the non-tumor tissues. CONCLUSION: It can be concluded that melatonin treatment attenuated DLL4 expression only in estrogen- responsive breast cancer cells and is able to induce apoptosis in breast cancer cells.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/metabolism , Breast Neoplasms/drug therapy , Calcium-Binding Proteins/metabolism , Estrogens/metabolism , Melatonin/pharmacology , Adaptor Proteins, Signal Transducing/antagonists & inhibitors , Antioxidants/pharmacology , Apoptosis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Calcium-Binding Proteins/antagonists & inhibitors , Cell Line, Tumor , Cell Proliferation , Female , Humans , Middle Aged , Patents as Topic , Signal TransductionABSTRACT
INTRODUCTION: Breast cancer is a heterogeneous and multifactorial disease. TP53 and PAI-1 as important tumor suppressor genes are involved in the development, invasion, and metastasis of many cancers. This study's objective was to demonstrate the combined genotype effects of these 2 genes by investigating their single nucleotide polymorphisms. METHODS: In this case-control study, 200 individuals with breast cancer and 179 healthy individuals were studied. The genotypes were determined using the tetra-ARMS method. For data analysis, MDR, online javstat statistics package, and SPSS v.24 software were used. Also, in silico studies on the estimated effects of each of these polymorphisms were performed. RESULTS: We showed a novel gene-gene interaction of these 2 genes and demonstrated a strong synergistic interaction for TP53/PAI-1, moderate synergistic interaction for PAI-1/age, and correlation for TP53/age. On the other hand, there was no association between the allelic and genotype frequency alone and in combination, with case-control status, using the parametric method, between TP53 and PAI-1. DISCUSSION/CONCLUSION: Our findings suggest that the polymorphism of codon 72 of the TP53 gene was significantly associated with tumor stage (p < 0.023). In conclusion, we showed a gene-gene interaction between TP53 and PAI-1, in combination, using the MDR method.
Subject(s)
Breast Neoplasms , Plasminogen Activator Inhibitor 1 , Breast Neoplasms/genetics , Case-Control Studies , Female , Genetic Predisposition to Disease , Genotype , Humans , Multifactor Dimensionality Reduction , Plasminogen Activator Inhibitor 1/genetics , Polymorphism, Single Nucleotide/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
Among the cancer susceptibility genes, TP53 is one of the crucial genes involved in cell cycle regulations and, therefore, it greatly affects breast cancer initiation and progression. In addition, WRAP53-a natural antisense transcript-regulates TP53 transcription and, as a protein, modulates the normal cell cycle, which results in breast cancer susceptibility. In this study, we aimed to analyze a haplotype comprising four SNPs, including rs1042522, rs17878362, rs2287499, and rs2287498, which are located at 5' regions of the TP53 and WRAP53 genes, in 118 patients and 110 healthy controls of the Iranian-Azeri population. In silico studies were conducted using the SIFT, Polyphen2, Fanthmm, RNAsnp, and SNP&GO online servers. Linkage disequilibrium (LD) and D' for each combination of the markers were calculated via the Haploview program. Our results showed that the GA1CC haplotype was the most frequent in the studied population. Additionally, no significant LD between any pairwise haplotypes was observed. The GA1CC and CA2GC haplotypes were significantly associated with breast cancer susceptibility. Moreover, the in silico analysis revealed the negative effects of rs2287499 and rs1042522 on WRAP53 and P53, respectively. In conclusion, the CA1GC haplotype was strongly identified as a breast cancer risk factor, and the GA1CC haplotype was assumed to be a protective factor against breast cancer risk. Hence, these markers may potentially be used as molecular prognostic and predictive biomarkers for breast cancer.
