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1.
Mol Cell Probes ; 74: 101955, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479679

ABSTRACT

Recurrent implantation failure (RIF) is a condition with a multifactorial basis. Recent research has focused on the role of genetic factors in the pathophysiology of RIF. Of particular note, miRNAs have been found to contribute to the pathogenesis of RIF. Several miRNA polymorphisms have been investigated in this context. Moreover, dysregulation of expression of a number of miRNAs, including miR-374a-5p, miR-145-5p, miR-30b-5p, miR-196b-5p, miR-22, miR-181 and miR-145 has been found in RIF. This review concentrates on the role of miRNAs in RIF to help in identification of the molecular basis for this condition and design of more effective methods for management of RIF, especially in a personalized manner that relies on the expression profiles of miRNAs in the peripheral blood or endometrium.


Subject(s)
MicroRNAs , Female , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Embryo Implantation/genetics
2.
Noncoding RNA Res ; 9(2): 367-375, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38511058

ABSTRACT

Circular RNAs (circRNAs) characterize a novel kind of regulatory RNAs distinguished by great evolutionary conservation and constancy. Although their exact role in malignancies is not fully understood, they mainly work through specific axes. Circular RNA/miRNA/mRNA axes affect the pathogenesis of human cancers including breast cancer. We assessed the expression and function of circ_0009910/miR-145-5p/MUC1 axis in Breast Cancer tissues and MCF-7 cells. Expression levels of circ_0009910 and MUC1 were notably increased in breast cancer tissues compared with control tissues, parallel with the down-regulation of miR-145-5p. Clinicopathological analysis indicated that up-regulation of circ_0009910 in breast tumors is related to invasion of the tumor to lymph node (P value = 0.011). Also, the downregulation of miR-145-5p was significantly correlated with tumor invasion to lymph nodes (P value = 0.04) and HER2-negative tumors (P value = 0.037). Finally, overexpression of MUC1 was correlated with age under 45 years (P value = 0.002). More importantly, circ_0009910-siRNA decreased the proliferation and migration ability of breast cancer cells, enhanced expression of miR-145-5p, and decreased levels of MUC1. Taken together, the circ_0009910/miR-145-5p/MUC1 axis has been demonstrated to affect the pathogenesis of breast cancer and might provide a target for breast cancer treatment.

3.
Pathol Res Pract ; 247: 154542, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37244050

ABSTRACT

Considering the burden of cancer, a number of methods have been applied to control or stop it. However, because of drug resistance or cancer recurrence, these treatments usually face failure. Combination of modulation of expression of non-coding RNAs (ncRNAs) with other treatments can increase treatment-sensitivity of tumors but these approaches still face some challenges. Gathering information in this field is a prerequisite to find more efficient cures for cancer. Cancer cells use ncRNAs to enhance uncontrolled proliferation originated from inactivation of cell death routs. In this review article, the main routes of cell death and involved ncRNAs in these routes are discussed. Moreover, extant information in the role of different ncRNAs on cell death pathways involved in the treatment resistance and cancer recurrence is summarized.


Subject(s)
Neoplasms , RNA, Long Noncoding , Humans , RNA, Untranslated/genetics , Neoplasms/genetics , Cell Death/genetics
4.
Front Mol Biosci ; 10: 1115996, 2023.
Article in English | MEDLINE | ID: mdl-36876051

ABSTRACT

Ferroptosis is a kind of cell death which has distinctive features differentiating it from autophagy, necrosis and apoptosis. This iron-dependent form of cell death is described by an increase in lipid reactive oxygen species, shrinkage of mitochondria and decrease in mitochondrial cristae. Ferroptosis is involved in the initiation and progression of many diseases and is regarded as a hotspot of investigations on treatment of disorders. Recent studies have shown that microRNAs partake in the regulation of ferroptosis. The impact of microRNAs on this process has been verified in different cancers as well as intervertebral disc degeneration, acute myocardial infarction, vascular disease, intracerebral hemorrhage, preeclampsia, hemorrhagic stroke, atrial fibrillation, pulmonary fibrosis and atherosclerosis. miR-675, miR-93, miR-27a, miR-34a and miR-141 have been shown to affect iron metabolism, antioxidant metabolism and lipid metabolism, thus influencing all pivotal mechanisms in the ferroptosis process. In the current review, we summarize the role of microRNAs in ferroptosis and their involvement in the pathetiology of malignant and non-malignant disorders.

5.
Biochem Genet ; 61(4): 1487-1508, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36645554

ABSTRACT

Previous investigations have revealed that circular RNAs (circRNAs) play pivotal roles in cancer development and progression by participating in several biological procedures, such as competing endogenous RNA (ceRNA) networks. Recently, circRNAs have been proposed as non-invasive, stable, and affordable cell-free biomarkers for cancer screening and test monitoring. Although, their clinical usefulness vastly remains to be evaluated in breast cancer (BC). Triple-negative breast cancer (TNBC), as the most challenging BC subtype, is an urgent requirement of identifying specific biomarkers and discovering the molecular mechanisms that lead to aggressive behaviors of tumor cells. The therapeutic strategies for TN patients have remained limited due to the impracticality of endocrine therapies and a remarkable portion of patients with TNBC experience recurrence, chemoresistance, and metastasis. TNBC Microarray expression profile analysis found that circ_0000977 is one of the most dysregulated circRNA in TNBC in comparison with non-TNBC. It could be a clue referring to the potential clinical utility of circ_0000977 in TNBC. The current study aims to assess the clinical implications and potential ceRNA regulatory network of circ_0000977 in TNBC. We confirmed circ_0000977 down-regulation in TNBC cell lines and tumors versus non-TNBC samples by real-time PCR. Subsequently, an assessment of the diagnostic value of circ_0000977 in plasma samples from triple-negative patients revealed a potential diagnostic cell-free biomarker in triple-negative BC. Finally, our integrative approach uncovered potential circ-0000977/miR-135b-5p/mRNAs regulatory network in TNBC. The inhibitory effect of miR-135b-5p on its downstream mRNAs was assessed by knocking down it in MDA-MB-231 cells. Functional and correlation analyses revealed APC and GATA3 could be regulated by circ_0000977/miR-135b-5p ceRNA axis, which presents valuable insight into circ-0000977-mediated gene silencing involved in the ceRNA network of TNBC. This study uncovered the potential clinical implication of circ_0000977 for the diagnosis and treatment of TNBC patients.


Subject(s)
MicroRNAs , Triple Negative Breast Neoplasms , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , RNA, Messenger , Biomarkers , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic
6.
Front Genet ; 13: 973585, 2022.
Article in English | MEDLINE | ID: mdl-36147505

ABSTRACT

MicroRNA-135 (miR-135) is a microRNA which is involved in the pathoetiology of several neoplastic and non-neoplastic conditions. Both tumor suppressor and oncogenic roles have been reported for this miRNA. Studies in prostate, renal, gallbladder and nasopharyngeal cancers as well as glioma have shown down-regulation of miR-135 in cancerous tissues compared with controls. These studies have also shown the impact of miR-135 down-regulation on enhancement of cell proliferation and aggressive behavior. Meanwhile, miR-135 has been shown to be up-regulated in bladder, oral, colorectal and liver cancers. Studies in breast, gastric, lung and pancreatic cancers as well as head and neck squamous cell carcinoma have reported dual roles for miR-135. Dysregulation of miR-135 has also been noted in various non-neoplastic conditions such as Alzheimer's disease, atherosclerosis, depression, diabetes, Parkinson, pulmonary arterial hypertension, nephrotic syndrome, endometriosis, epilepsy and allergic conditions. In the current review, we summarize the role of miR-135 in the carcinogenesis as well as development of other disorders.

7.
Exp Mol Pathol ; 128: 104819, 2022 10.
Article in English | MEDLINE | ID: mdl-35914612

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) has become one of the most common cancers in recent years. Given the importance that non-coding RNAs have recently acquired in various diseases including cancers, we decided to design this study to evaluate the expression levels of circ0001955/miR-145-5p/ONECUT2 axis in CRC. METHODS: After bioinformatics analysis of GEO datasets related to CRC, a putative circ0001955/ miR-145-5p/ ONECUT2 pathway was assumed. Then, the expression levels of these genes were measured in 50 CRC samples and adjacent tissues by qRT- PCR. Also, correlation coefficients, receiver operating characteristic (ROC) curves, and correlation between circ0001955 levels with clinicopathological parameters of patients were analyzed. RESULTS: Circ0001955 and ONECUT2 were considerably up-regulated, while the expression level of miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0001955, miR-145-5p, and ONECUT2. We did not find any significant correlation between circ0001955 expression and clinicopathological parameters. CONCLUSION: Our study showed that circ0001955 is dysregulated in CRC. This finding can open a new window for researchers for a better understanding of the potential pathways involved in CRC pathogenesis and, consequently, to find new treatment pathways.


Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic/genetics , Cell Proliferation , Transcription Factors/genetics , Homeodomain Proteins/genetics
8.
Front Genet ; 13: 950162, 2022.
Article in English | MEDLINE | ID: mdl-36035118

ABSTRACT

Recent studies have revealed important functions of several microRNAs (miRNAs) in the pathogenesis of human diseases. miR-324 is an example of miRNAs with crucial impacts on the pathogenesis of a wide range of disorders. Gene ontology studies have indicated possible role of miR-324 in responses of cells to the leukemia inhibitory factor, long-term synaptic potentiation, positive regulation of cytokines production and sensory perception of sound. In human, miR-324 is encoded by MIR324 gene which resides on chromosome 17p13.1. In the current manuscript, we provide a concise review of the role of miR-324 in the pathogenesis of cancers as well as non-cancerous conditions such as aneurysmal subarachnoid hemorrhage, diabetic nephropathy, epilepsy, pulmonary/renal fibrosis, ischemic stroke and ischemia reperfusion injuries. Moreover, we summarize the role of this miRNA as a prognostic marker for malignant disorders.

9.
Gene Rep ; 28: 101641, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35875722

ABSTRACT

Coronavirus disease 2019 (COVID-19) is regarded as a challenge in health system. Several studies have assessed the immune-related aspect of this disorder to identify the host-related factors that affect the course of COVID-19. microRNAs (miRNAs) as potent regulators of immune responses have gained much attention in this regard. Recent studies have shown aberrant expression of miRNAs in COVID-19 in association with disease course. Differentially expressed miRNAs have been enriched in pathways related with inflammation and antiviral immune response. miRNAs have also been regarded as potential therapeutic targets in COVID-19, particularly for management of pathological consequences of COVID-19. In the current review, we summarize the data about dysregulation of miRNAs in COVID-19.

10.
Article in English | MEDLINE | ID: mdl-35718959

ABSTRACT

BACKGROUND: Reactivation of HbF is a potential strategy to ameliorate symptoms of hemoglobinopathies such as sickle cell disease and b-thalassemia. After birth, there is a switch from fetal to adult hemoglobin, for which the molecular mechanisms and key regulators await further understanding in order to develop effective methods for HbF reactivation. Bcl11a, one of the major HbF reactivation regulators, demonstrates no significant changes at transcriptional levels in F erythroblasts compared to the non-HbF expressing cells. Therefore, it is possible that posttranscriptional regulation and epigenetic effects, for which the miRNAs play an important role, are the primary causes of the decreased Bcl11a protein level in adult erythroblasts. OBJECTIVE: This paper aims to determine the differentially expressed mRNAs and miRNAs of erythroblasts in HSCs from the fetal liver and bone marrow. METHODS: Raw high-throughput sequencing data (GSE110936, GSE90878) was downloaded from Gene Expression Omnibus (GEO) database. After RNAseq analysis, several data sets and tools were used to select key genes and examine selection validation. RESULTS: We selected 42 DEmRNAs and nine DEmiRs, including hsa-let-7f-5p, hsa-miR-21-5p, hsamiR- 22-3p, hsa-miR-126-5p, hsa-miR-146b-5p, hsa-miR-181a-5p, hsa-miR-92a-3p, hsa-miR-25-3p and hsa-miR-191-5p. Furthermore, hub genes including hist1h2bl, al133243.2, trim58, abcc13, bpgm, and fam210b were identified in the coexpression network, as well as RPS27A in the PPI network. Functional analysis revealed that these DEmRNAs and DEmiRs might play a role in gene expression regulation at multiple levels. Gene set enrichment analysis, in particular, revealed a possible role for genes in the globin switching process. CONCLUSION: According to our findings, a number of the DEmRNAs and DEmiRs may play significant roles in globin switching regulation and thus have the potential to be applied for HbF reactivation.


Subject(s)
Globins , MicroRNAs , Humans , Gene Expression Regulation , Globins/genetics , Globins/metabolism , MicroRNAs/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism
11.
BMC Cancer ; 22(1): 668, 2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35715772

ABSTRACT

The concept of the 'BRCAness' phenotype implies the properties that some sporadic breast cancers (BC) share with BRCA1/2-mutation carriers with hereditary BC. Breast tumors with BRCAness have deficiencies in homologous recombination repair (HRR), like BRCA1/2-mutation carriers, and consequently could benefit from poly-(ADP)-ribose polymerase (PARP) inhibitors and DNA-damaging chemotherapy. Triple-negative breast cancers (TNBC) show a higher frequency of BRCAness than the other BC subtypes. Therefore, looking for BRCAness-related biomarkers could improve personalized management of TNBC patients. microRNAs (miRNAs) play a pivotal role in onco-transcriptomic profiles of tumor cells besides their suitable features as molecular biomarkers. The current study aims to evaluate the expression level of some critical miRNAs-mRNA axes in HRR pathway in tumors and plasma samples from BC patients. The expression levels of three multi-target miRNAs, including miR-182-5p, miR-146a-5p, and miR-498, as well as six downstream HRR-related protein-coding genes, have been investigated in the breast tumors and paired adjacent normal tissues by Real-time PCR. In the next step, based on the results derived from the previous step, we examined the level of cell-free miR-182-5p in the blood plasma samples from the patients. Our results highlight the difference between TNBC and non-TNBC tumor subgroups regarding the dysregulation of the key miRNA/mRNA axes involved in the HRR pathway. Also, for the first time, we show that the level of cell-free miR-182-5p in plasma samples from BC patients could be a clue for screening BC patients eligible for receiving PARP inhibitors through a personalized manner. Altogether, some sporadic BC patients, especially sporadic TNBC, have epigenetically dysregulated HRR pathway that could be identified and benefit from BRCAness-specific therapeutic agents.


Subject(s)
MicroRNAs , Triple Negative Breast Neoplasms , BRCA1 Protein/biosynthesis , BRCA1 Protein/genetics , BRCA2 Protein/biosynthesis , BRCA2 Protein/genetics , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology
12.
Mol Biol Rep ; 49(10): 9759-9765, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35441941

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) have been recently shown to exert several functional roles in the development and function of neurons. Moreover, numerous miRNAs are present in high abundance in presynaptic and postsynaptic sites regulating synaptic plasticity and activity through different mechanisms. METHODS: We searched PubMed and Google Scholar databases with key words "Synaptic plasticity", "miRNA" and "major depressive disorder. RESULTS: Synaptic plasticity has an essential role in the ability of the brain to integrate transitory experiences into constant memory traces. Thus, it participates in the development of neuropsychiatric diseases such as major depressive disorder (MDD). Most notably, MDD-related alterations in synaptic function have been found to be closely related with abnormal expression of miRNAs. CONCLUSIONS: Several miRNAs such as miR-9-5p, miR-204-5p, miR-128-3, miR-26a-3p, miR-218, miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p, miR-323a-3p, miR-425-5p, miR-34a, miR-137, miR-204-5p, miR-99a, miR-134, miR-124-3p and miR-3130-5p have been shown to be involved in the regulation of synaptic plasticity in the context of MDD. In the current review, we elaborate the role of miRNAs in regulation of this important neuronal feature in MDD.


Subject(s)
Depressive Disorder, Major , MicroRNAs , Depression , Depressive Disorder, Major/genetics , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Neuronal Plasticity/genetics
13.
Cancer Cell Int ; 22(1): 105, 2022 Mar 05.
Article in English | MEDLINE | ID: mdl-35248081

ABSTRACT

miR-630 is encoded by MIR630 gene (NC_000015.10) on 15q24.1. This miRNA is mostly associated with cytokine signaling in immune system. Several neoplastic as well as non-neoplastic conditions have been linked with dysregulation of miR-630. It is an oncogenic miRNA in renal cell carcinoma, multiple myeloma, colorectal cancer, acute lymphoblastic leukemia, ovarian cancer and prostate cancer. On the other hand, it is a putative tumor suppressor miRNA in lung, cervical, breast, thyroid and esophageal tissues. In a number of other tissues, data regarding the role of miR-630 in the carcinogenesis is conflicting. Expression levels of miR-630 can be used as markers for prediction of cancer course. Moreover, miR-630 can influence response to chemoradiotherapy. This miRNA is also involved in the pathoetiology of IgA nephropathy, obstructive sleep apnea, age-related nuclear cataract and vitiligo. In the present review, we discuss the role of miR-630 in these conditions.

14.
Pathol Res Pract ; 231: 153780, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35101714

ABSTRACT

miR-145-5p is a microRNA whose role in diverse disorders has been verified. This miRNA is encoded by MIR145 gene on chromosome 5. This miRNA is mainly considered as a tumor suppressor miRNA in diverse types of cancers, including bladder cancer, breast cancer, cervical cancer, cholangiocarcinoma, renal cancer, and gastrointestinal cancers. However, few studies have reported up-regulation of this miRNA in some cancers. Moreover, it has been shown to affect pathogenesis of a number of non-malignant conditions such as aplastic anemia, asthma, cerebral ischemia/reperfusion injury, diabetic nephropathy, rheumatoid arthritis and Sjögren syndrome. In the current review, we summarize the available literature about the role of miR-145-5p in these conditions.


Subject(s)
Breast Neoplasms/genetics , MicroRNAs/metabolism , Stomach Neoplasms/genetics , Urinary Bladder Neoplasms/genetics , Breast Neoplasms/etiology , Breast Neoplasms/physiopathology , Down-Regulation/genetics , Gene Expression Profiling/methods , Gene Expression Profiling/statistics & numerical data , Humans , MicroRNAs/analysis , MicroRNAs/genetics , Stomach Neoplasms/etiology , Stomach Neoplasms/physiopathology , Urinary Bladder Neoplasms/etiology , Urinary Bladder Neoplasms/physiopathology
15.
Biomed Pharmacother ; 144: 112334, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34656064

ABSTRACT

Let-7 includes a family of miRNA which are implicated in the developmental processes as well as carcinogenesis. This miRNA family has been shown to influence pathogenesis of a variety of hematological malignancies through changing expression of a number of oncogenic pathways, particularly those related with MYC. Expression of these miRNAs has been found to be different between distinct hematological malignancies or even between cytogenetically-defined subgroups of a certain malignancy. In the current review, we summarize the data regarding biogenesis, genomic locations, targets and regulatory network of this miRNA family in the context of hematological malignancies.


Subject(s)
Hematologic Neoplasms/metabolism , MicroRNAs/metabolism , Animals , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , Hematologic Neoplasms/genetics , Hematologic Neoplasms/pathology , Humans , MicroRNAs/genetics , Signal Transduction
16.
World J Surg Oncol ; 19(1): 265, 2021 Sep 03.
Article in English | MEDLINE | ID: mdl-34479583

ABSTRACT

INTRODUCTION: Colorectal cancer (CRC) is one of the most frequent neoplasms in the world. Based on the emerging role of noncoding RNAs, particularly circular RNAs in pathogenesis of cancers, we designed this study to inspect the expression levels of a circ0009910-mediated regulatory pathway in colorectal cancer. METHODS: After bioinformatics analyses and construction of putative circ0009910/ miR-145-5p/PEAK1 pathway, the expression levels of these components were evaluated in 50 CRC tissues and adjacent specimens by quantitative real-time PCR. Moreover, we appraised the correlation coefficients between these transcripts and calculated the correlation between circ0009910 expression levels with clinicopathological features of patients. RESULTS: Circ0009910 and PEAK1 were significantly upregulated, while miR-145-5p was decreased in CRC samples compared with adjacent tissues (p < 0.05). Moreover, statistically significant correlations were observed between expression levels of circ0009910, miR-145-5p, and PEAK1. We also reported considerable correlations between circ0009910 expression and clinicopathological parameters including sex and perineural invasion. Finally, ROC curve analysis showed circ0009910 level as a discriminative biomarker for CRC. CONCLUSION: For the first time, we could introduce circ0009910 as an important biomarker in CRC. Collectively, this investigation helped us to identify a newly diagnosed pathway in CRC that can be a potential axis for designing effective drugs for treatment of CRC patients.


Subject(s)
Colorectal Neoplasms , MicroRNAs , Protein-Tyrosine Kinases/metabolism , RNA, Circular/genetics , Cell Proliferation , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Prognosis
17.
Cancer Cell Int ; 21(1): 312, 2021 Jun 14.
Article in English | MEDLINE | ID: mdl-34126989

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) have been implicated in the initiation and development of breast cancer as functional non-coding RNAs (ncRNA). The roles of circRNAs as the competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs) have also been indicated. However, the functions of circRNAs in breast cancer have not been totally elucidated. This study aimed to explore the clinical implications and possible roles of circ_0044234 in carcinogenesis of the most problematic BC subtype, triple negative breast cancer (TNBC), which are in desperate need of biomarkers and targeted therapies. METHODS: The importance of circ_0044234 as one of the most dysregulated circRNAs in TNBC was discovered through microarray expression profile analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the downregulation of circ_0044234 in triple negative tumors and cell lines versus non-triple negative ones. The bioinformatics prediction revealed that circ_0044234 could act as an upstream sponge in the miR-135b/GATA3 axis, two of the most dysregulated transcripts in TNBC. RESULTS: Our experimental investigation of circ_0044234 expressions in various BC subtypes as well as cell lines reveals that TNBC expresses circ_0044234 at a substantially lower level than non-TNBC. The ROC curve analysis indicates that it could be applied as a discriminative biomarker to identify TNBC from other BC subtypes. Moreover, circ_0044234 expression could be an independent prognostic biomarker in BC. Interestingly, a substantial inverse expression correlation was detected between circ_0044234 and miR-135b-5p as well as between miR-135b-5p and GATA3 in breast tumors. CONCLUSIONS: The possible clinical usefulness of circ_0044234 as a promising distinct biomarker and upcoming therapeutic target for TNBC have been indicated in this research. Our comprehensive approach revealed the potential circ_0044234/miR135b-5p/GATA3 ceRNA axis in TNBC.

18.
Gastroenterol Hepatol Bed Bench ; 14(2): 141-153, 2021.
Article in English | MEDLINE | ID: mdl-33968341

ABSTRACT

AIM: The aim of this study was to integrate both coding and non-coding available microarray data in the development of colorectal cancer (CRC) with bioinformatics analyses to attain a more inclusive pathobiologic map of their molecular interactions and functions. BACKGROUND: Identification of competing endogenous RNAs (ceRNAs), especially circRNAs, has become a new hotspot in cancer research, although their roles and underlying mechanisms in CRC development remain mostly unknown. METHODS: Microarray data was retrieved from the Gene Expression Omnibus (GEO) database and analyzed. Several bioinformatics tools and databases were applied for further elucidation. Principal component analysis (PCA) was run separately for four datasets. The dysregulated circRNA-miRNA-mRNA, co-expression, and protein-protein interaction (PPI) networks were established. RESULTS: PCA discloses colorectal tumors; normal tissue can be distinguished not only by mRNAs expression profile, but also by both circRNA and miRNA expression profiles. In this study, 14 DE mRNAs, 85 DE miRNAs, and 36 DE circRNAs were identified in CRC tissue and compared with normal tissue. Taking their potential interactions into account, a circRNA-miRNA-mRNA network was constructed. The results disclosed some DE circRNAs with potential oncogenic (circ_0014879) or tumor suppressive (circ_0001666 and circ_0000977) effects. Finally, the PPI network suggests pivotal roles for DOCK2 and PTPRC dysregulation in the progression of CRC, possibly by facilitating tumor escape from immune surveillance. CONCLUSION: The current study proposes a novel regulatory network consisting of DE circRNAs, miRNAs, and mRNAs in CRC development that highlights the roles of DE circRNAs at the upstream of oncotranscriptomic cascade in CRC development, suggesting their potential to be utilized as both prognostic and therapeutic biomarkers.

19.
Int J Mol Sci ; 23(1)2021 Dec 30.
Article in English | MEDLINE | ID: mdl-35008841

ABSTRACT

miR-149 is an miRNA with essential roles in carcinogenesis. This miRNA is encoded by the MIR149 gene on 2q37.3. The miR-149 hairpin produces miR-149-5p and miR-149-3p, which are the "guide" and the sister "passenger" strands, respectively. Deep sequencing experiments have shown higher prevalence of miR-149-5p compared with miR-149-3p. Notably, both oncogenic and tumor suppressive roles have been reported for miR-149-5p. In this review, we summarize the impact of miR-149-5p in the tumorigenesis and elaborate mechanisms of its involvement in this process in a variety of neoplastic conditions based on three lines of evidence, i.e., in vitro, in vivo and clinical settings.


Subject(s)
Carcinogenesis/genetics , MicroRNAs/metabolism , Animals , Carcinogenesis/pathology , Cell Line, Tumor , Disease Models, Animal , Gene Ontology , Gene Regulatory Networks , Genes, Tumor Suppressor , Humans , MicroRNAs/genetics
20.
Cancer Rep (Hoboken) ; 3(6): e1286, 2020 12.
Article in English | MEDLINE | ID: mdl-32886452

ABSTRACT

BACKGROUND: Ovarian (OV) cancer is considered as one of the most deadly malignancies in women, since it is unfortunately diagnosed in advanced stages. Nowadays, the importance of bioinformatics tools and their frequent usage in tracking dysregulated cancer-related genes and pathways have been highlighted in researches. AIM: The aim of this study is to investigate dysregulated miRNAs-genes network and its function in OV tumors based on the integration of microarray data through a system biology approach. METHODS: Two microarray data (GSE119056 and GSE4122) were analyzed to explore the differentially expressed miRNAs (DEmiRs) and genes among OV tumors and normal tissues. Then, through the help of TargetScan, miRmap, and miRTarBase databases, the dysregulated miRNA-gene network in OV tumors was constructed by Cytoscape. In the next step, co-expression and protein-protein interaction networks were made using GEPIA and STRING databases. Moreover, the functional analysis of the hub genes was done by DAVID, KEGG, and Enrichr databases. Eventually, the regulatory network of TF-miRNA-gene was constructed. RESULTS: The potential dysregulated miRNAs-genes network in OV tumors has been constructed, including 109 differentially expressed genes (DEGs), 25 DEmiRs, and 213 interactions. Two down-regulated microRNAs, miR-660-3p and hsa-miR-4510, have the most interactions with up-expressed oncogenic DEGs. CDK1, PLK1, CCNB1, CCNA2, and EZH2 are involved in protein module, which show significant overexpression in OV tumors according to The Cancer Genome Atlas (TCGA) data. EZH2 shows amplification in OV tumors with remarkable percentage. The transcription factors TFAP2C and GATA4 have the pivotal regulatory functions in oncotranscriptomic profile of OV tumors. CONCLUSION: In current study, we have collected and integrated different data to uncover the complex molecular interactions and oncomechanisms in OV tumors. The DEmiRs-DEGs and TF-miRNA-gene networks reveal the potential interactions that could be a significant piece of the OV onco-puzzle.


Subject(s)
Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , MicroRNAs/analysis , Ovarian Neoplasms/genetics , Computational Biology , Female , Humans , Microarray Analysis , Ovarian Neoplasms/etiology , Protein Interaction Maps , Transcription Factors/genetics
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