Clinical and In Silico Outcomes of miR-130a-5p and miR-615-3p Expression in Tumor Compared with Non-Tumor Adjacent Tissues of Patients with BC

Background: Breast cancer (BC) is the most common malignancy among women with a high mortality rate. The blockade of asparagine-related pathways may be an effective measurement to control the progression and reduction of BC metastasis potential. Recently, it has been shown that various miRNAs, as part of small non-coding RNAs, have a great role in cancer development, especially asparagine-related pathways, to modulate the invasiveness. Objective: This study aimed to evaluate the expression of miR-130a-5p and miR-615-3p in tumoral and non-tumoral adjacent tissues of patients with BC. Methods: There is a chance that asparagine metabolism is influenced by miR-130a-5p and miR-615-3p confirmed by bioinformatics analysis. Hence, real-time PCR was conducted on eighty BC tumoral and non-tumoral adjacent tissues to evaluate the expression level of the two miRNAs. To predict the potential biological process and molecular pathways of miR-130a-5p, in-silico analysis was performed. Results: This study indicated that miR-130a was downregulated in tumoral tissues compared to non-tumoral adjacent tissues (P-value= 0.01443 and fold change= -2.5137), while miR-615-3p did not show a significant difference between the two groups. Furthermore, the subgroup studies did not reveal any significant correlation between the expression of these two miRNAs and subfactors. Furthermore, insilico studies unraveled several biological processes related to amino-acid metabolism, as well as pathways related to tumor development such as Phosphatase and Tensin Homolog (PTEN) and JAK-STAT pathways among miR-130a-5p target genes. Conclusion: Our findings indicate that miRNA-130a-5p is downregulated in BC tissues and may play a tumor suppressor role in patients with BC. Therefore, it may be suggested as a potential diagnostic and therapeutic target for BC.

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The Expression of miR-513c and miR-3163 was Downregulated in Tumor Tissues Compared with Margin Tissues of Patients With Breast Cancer

10.21203/rs.3.rs-28926/v1 ◽

2020 ◽

Author(s):

Soheila Delgir ◽

Khandan Ilkhani ◽

Asma Safi ◽

Farhad Seif ◽

Milad Bastami ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

In Silico ◽

In Silico Analysis ◽

Glutamine Metabolism ◽

Expression Level ◽

P Value ◽

Biological Processes ◽

Tumor Tissues ◽

Silico Analysis

Abstract Background Breast cancer (BC) is the most common invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered a critical nutrition for tumor cell growth and therefore, targeting glutamine metabolism, especially Glutaminase, which catalyzed the conversion of glutamine to glutamate can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with short length and single strand properties play a significant role in regulating the genes related to glutamine metabolism and may control the development of cancer.Methods Since, 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 margin tissues. The data were analyzed to evaluate the correlation between expression level of these miRNAs and patient’s characteristics such as abortion history, family history, and age. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on its gene targets.Results In-silico studies revealed the top categories of biological processes and pathways that play a critical role in cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (P-value = 0.02062 and fold change= -2.3801) and miR-3163 (P-value = 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup studies did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion.Conclusion Based on our data, miR-513c and miR-3163 may be offered as a potential diagnosis and therapeutic targets for patients with BC.

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In silico approach of naringin as potent phosphatase and tensin homolog (PTEN) protein agonist against prostate cancer

Journal of Biomolecular Structure and Dynamics ◽

10.1080/07391102.2020.1830855 ◽

2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Sankar Muthumanickam ◽

Thangamariyappan Indhumathi ◽

Pandi Boomi ◽

Ramachandran Balajee ◽

Jeyaraman Jeyakanthan ◽

...

Keyword(s):

Prostate Cancer ◽

In Silico ◽

Pten Protein ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

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Contribution of mTOR and PTEN to Radioresistance in Sporadic and NF2-Associated Vestibular Schwannomas: A Microarray and Pathway Analysis

Cancers ◽

10.3390/cancers12010177 ◽

2020 ◽

Vol 12 (1) ◽

pp. 177 ◽

Cited By ~ 1

Author(s):

Isabel Gugel ◽

Florian H. Ebner ◽

Florian Grimm ◽

Stefan Czemmel ◽

Frank Paulsen ◽

...

Keyword(s):

Pathway Analysis ◽

Radiation Treatment ◽

Mammalian Target Of Rapamycin ◽

Neurofibromatosis Type ◽

P Value ◽

Mtor Inhibition ◽

Phosphatase And Tensin Homolog ◽

Molecular Alterations ◽

Tensin Homolog ◽

Systemic Treatments

The use of radiation treatment has increased for both sporadic and neurofibromatosis type 2 (NF2)-associated vestibular schwannoma (VS). However, there are a subset of radioresistant tumors and systemic treatments that are seldom used in these patients. We investigated molecular alterations after radiation in three NF2-associated and five sporadically operated recurrent VS after primary irradiation. We compared these findings with 49 non-irradiated (36 sporadic and 13 NF2-associated) VS through gene-expression profiling and pathway analysis. Furthermore, we stained the key molecules of the distinct pathway by immunohistochemistry. A total of 195 differentially expressed genes in sporadic and NF2-related comparisons showed significant differences based on the criteria of p value < 0.05 and a two-fold change. These genes were involved in pathways that are known to be altered upon irradiation (e.g., mammalian target of rapamycin (mTOR), phosphatase and tensin homolog (PTEN) and vascular endothelial growth factor (VEGF) signaling). We observed a combined downregulation of PTEN signaling and an upregulation of mTOR signaling in progressive NF2-associated VS after irradiation. Immunostainings with mTOR and PTEN antibodies confirmed the respective molecular alterations. Taken together, mTOR inhibition might be a promising therapeutic strategy in NF2-associated VS progress after irradiation.

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FRUITFULL Is a Repressor of Apical Hook Opening in Arabidopsis thaliana

International Journal of Molecular Sciences ◽

10.3390/ijms21176438 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6438

Author(s):

Miriam Führer ◽

Angelika Gaidora ◽

Peter Venhuizen ◽

Jedrzej Dobrogojski ◽

Chloé Béziat ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

In Silico ◽

Target Genes ◽

Growth Promotion ◽

In Silico Analysis ◽

Regulatory Elements ◽

Suitable Model ◽

Differential Growth ◽

Apical Hook ◽

Growth Transitions

Plants adjust their architecture to a constantly changing environment, requiring adaptation of differential growth. Despite their importance, molecular switches, which define growth transitions, are largely unknown. Apical hook development in dark grown Arabidopsis thaliana (A. thaliana) seedlings serves as a suitable model for differential growth transition in plants. Here, we show that the phytohormone auxin counteracts the light-induced growth transition during apical hook opening. We, subsequently, identified genes which are inversely regulated by light and auxin. We used in silico analysis of the regulatory elements in this set of genes and subsequently used natural variation in gene expression to uncover correlations between underlying transcription factors and the in silico predicted target genes. This approach uncovered that MADS box transcription factor AGAMOUS-LIKE 8 (AGL8)/FRUITFULL (FUL) modulates apical hook opening. Our data shows that transient FUL expression represses the expression of growth stimulating genes during early phases of apical hook development and therewith guards the transition to growth promotion for apical hook opening. Here, we propose a role for FUL in setting tissue identity, thereby regulating differential growth during apical hook development.

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Adiponectin Haploinsufficiency Promotes Mammary Tumor Development in MMTV-PyVT Mice by Modulation of Phosphatase and Tensin Homolog Activities

PLoS ONE ◽

10.1371/journal.pone.0004968 ◽

2009 ◽

Vol 4 (3) ◽

pp. e4968 ◽

Cited By ~ 50

Author(s):

Janice B. B. Lam ◽

Kim H. M. Chow ◽

Aimin Xu ◽

Karen S. L. Lam ◽

Jing Liu ◽

...

Keyword(s):

Mammary Tumor ◽

Tumor Development ◽

Phosphatase And Tensin Homolog ◽

Tensin Homolog

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Chondroitin sulfate degradation and eicosanoid metabolism pathways are impaired in focal segmental glomerulosclerosis: Experimental confirmation of an in silico prediction

Bioimpacts ◽

10.15171/bi.2019.12 ◽

2019 ◽

Vol 9 (2) ◽

pp. 89-95

Author(s):

Shiva Kalantari ◽

Mohammad Naji ◽

Mohsen Nafar ◽

Hootan Yazdani-Kachooei ◽

Nasrin Borumandnia ◽

...

Keyword(s):

Chondroitin Sulfate ◽

Focal Segmental Glomerulosclerosis ◽

In Silico ◽

Target Genes ◽

In Silico Analysis ◽

Non Invasive ◽

Segmental Glomerulosclerosis ◽

Eicosanoid Metabolism ◽

Cox 2 ◽

Primary Glomerular Disease

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease, is a diverse clinical entity that occurs after podocyte injury. Although numerous studies have suggested molecular pathways responsible for the development of FSGS, many still remain unknown about its pathogenic mechanisms. Two important pathways were predicted as candidates for the pathogenesis of FSGS in our previous in silico analysis, whom we aim to confirm experimentally in the present study. Methods: The expression levels of 4 enzyme genes that are representative of "chondroitin sulfate degradation" and "eicosanoid metabolism" pathways were investigated in the urinary sediments of biopsy-proven FSGS patients and healthy subjects using real-time polymerase chain reaction (RT-PCR). These target genes were arylsulfatase, hexosaminidase, cyclooxygenase-2 (COX-2), and prostaglandin I2 synthase. The patients were sub-divided into 2 groups based on the range of proteinuria and glomerular filtration rate and were compared for variation in the expression of target genes. Correlation of target genes with clinical and pathological characteristics of the disease was calculated and receiver operating characteristic (ROC) analysis was performed. Results: A combined panel of arylsulfatase, hexosaminidase, and COX-2 improved the diagnosis of FSGS by 76%. Hexosaminidase was correlated with the level of proteinuria, while COX-2 was correlated with interstitial inflammation and serum creatinine level in the disease group. Conclusion: Our data supported the implication of these target genes and pathways in the pathogenesis of FSGS. In addition, these genes can be considered as non-invasive biomarkers for FSGS.

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In-silico analysis of BCL2 gene using multiple bioinformatics tools to identify the most lethal mutations that are crucial for its structural and functional integrity

10.21203/rs.3.rs-310735/v4 ◽

2021 ◽

Author(s):

Usman Ghani ◽

Yasir Ali ◽

Karim Gul ◽

Aamir sohail ◽

Rahmat Ullah ◽

...

Keyword(s):

Animal Models ◽

In Silico ◽

Tumor Development ◽

In Silico Analysis ◽

Vital Role ◽

Gene Interactions ◽

Bioinformatics Tools ◽

Apoptotic Activity ◽

And Function ◽

Related Proteins

Abstract BCL2 was the first ever known gene for anti-apoptotic activity, that encodes for essential proteins of the external mitochondrial membrane. Regarding tumorigenesis, deregulated BCL2 expression and related proteins have been recognized as characteristic of several human cancers and there is concrete evidence that the deregulated expression of BCL2 like proteins plays a vital role in tumor development, persistence and therapeutic resistance. Therefore, it is important to identify the polymorphisms of BCL2 that are both structurally and functionally important for research to find their possible malfunctions and therapeutics. For this reason, in our research, we have used a variety of bioinformatics tools to recognize the most destructive nsSNPs that may be important for the structure and function of BCL2. In silico tools, PROVEAN, SIFT, SNP&GO, PhD SNP, and PolyPhen2 included a variety of other tools such as I Mutant, MutPred, and ConSurf, to study their conservation profiles to validate their stability, structural, and functional impacts. Post-transcriptional alteration sites were also predicted followed by application of 3-D mapping with I-TASSER and Phyre2 tools. Furthermore, the gene interactions were mapped via STRING and GeneMANIA. We also found that nsSNPs Q118R (rs759928495), G193R (rs1197820694), R129C (rs777784952), and Ll81V (rs752310933) are the most destructive nsSNPs in BCL2 genes that can have a vital part in BCL2 protein defects and possibly cause different cancers. Gene-gene interactions showed relation of BCL2 with other genes depicting its importance in several pathways and co-expressions. This research is the first of its kind and offers future prospects for the development of dedicated medicines as well. In the animal models, the effects of BCL2 can also be tested in diseases. Such should be the study of BCL2 proteins from cancer patients. The effects of BCL2 can also be tested on animal models.

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Integrated In-silico Analysis to Study the Role of microRNAs in the Detection of Chronic Kidney Diseases

Current Bioinformatics ◽

10.2174/1574893614666190923115032 ◽

2020 ◽

Vol 15 (2) ◽

pp. 144-154

Author(s):

Amina Khan ◽

Andleeb Zahra ◽

Sana Mumtaz ◽

M. Qaiser Fatmi ◽

Muhammad J. Khan

Keyword(s):

Target Genes ◽

Kidney Development ◽

Kidney Diseases ◽

In Silico Analysis ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Renal Diseases ◽

P Value ◽

Chronic Kidney Diseases

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of various renal diseases, including Chronic Kidney Diseases (CKD). CKD refers to the gradual loss of kidney function with the declining Glomerular Functional Rate (GFR). Objective: This study focused on the regulatory mechanism of miRNA to control gene expression in CKD. Methods: In this context, two lists of Differentially Expressed Genes (DEGs) were obtained; one from the three selected experiments by setting a cutoff p-value of <0.05 (List A), and one from a list of target genes of miRNAs (List B). Both lists were then compared to get a common dataset of 33 miRNAs, each had a set of DEGs i.e. both up-regulated and down-regulated genes (List C). These data were subjected to functional enrichment analysis, network illustration, and gene homology studies. Results: This study confirmed the active participation of various miRNAs i.e. hsa -miR-15a-5p, hsa-miR-195-5p, hsa-miR-365-3p, hsa-miR-30a-5p, hsa-miR-124-3p, hsa-miR-200b-3p, and hsamiR- 429 in the dysregulation of genes involved in kidney development and function. Integrated analyses depicted that miRNAs modulated renal development, homeostasis, various metabolic processes, immune responses, and ion transport activities. Furthermore, homology studies of miRNA-mRNA hybrid highlighted the effect of partial complementary binding pattern on the regulation of genes by miRNA. Conclusion: The study highlighted the great values of miRNAs as biomarkers in kidney diseases. In addition, the need for further investigations on miRNA-based studies is also commended in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.

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The Role of Micrornas in Regulating Redox Modulation in Bipolar Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1909 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S119-S119

Author(s):

H. Kim ◽

K. Tyryshkin ◽

N. Elmi ◽

V. Oliviera ◽

A. Andreazza ◽

...

Keyword(s):

Bipolar Disorder ◽

Transcription Factors ◽

In Silico ◽

Target Genes ◽

In Silico Analysis ◽

Machine Learning Algorithms ◽

Validation Dataset ◽

Control Group ◽

Redox Modulation ◽

Validation Experiment

IntroductionAlterations in redox modulation are consistently reported in bipolar disorder (BD). MicroRNAs are targeted regulators of gene expression.Objectives and aimsWe aimed to examine if microRNAs that target redox modulators can discriminate between BD and healthy controls.MethodsData from brains of individuals with and without BD were obtained from Array Collection datasets. MicroRNAs targeting redox modulators were assessed for their ability to discriminate BD from the control group using machine-learning algorithms. Methylation of microRNAs, expression of their transcription factors and redox targets were assessed with ANCOVA with FDR correction. For validation, we acquired plasma samples belonging to 2 families of individuals with and without BD (n = 9). Plasma microRNAs were sequenced using the Ion Total RNA Sequencing Kit (Thermo Fisher Scientific), and microRNAs identified from the in silico analysis were examined in the validation dataset.ResultsWe identified 5 miRNAs (hsa-miR-299, hsa-miR-125a, hsa-miR-145, hsa-miR-30b, hsa-miR424) that were common in two of the four in silico datasets. Target genes glutathione peroxidase 4, ATP5A1, ATP5G1, NDUFS1, NDUFC2, and catalase were expressed at different levels between BD and the control group. Furthermore, our results showed that transcription factors CTCF and USF1 might control the expression of hsa-miR-145, while methylation differences were not found. Finally, hsa-miR-30b was significantly increased in the plasma of patients with BD compared to controls in the validation experiment.ConclusionsOur study demonstrates that microRNAs may have an important role in the initiation of redox changes in BD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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The Expression of miR-513c and miR-3163 was Downregulated in Tumor Tissues Compared with Margin Tissues of Patients with Breast Cancer

10.21203/rs.3.rs-136137/v1 ◽

2020 ◽

Author(s):

Soheila Delgir ◽

Khandan Ilkhani ◽

Asma Safi ◽

Vahid Montazari ◽

Farhad Seif ◽

...

Keyword(s):

Breast Cancer ◽

In Silico ◽

In Silico Analysis ◽

Fold Change ◽

Glutamine Metabolism ◽

P Value ◽

Biological Processes ◽

Tumor Tissues ◽

In Silico Studies ◽

Silico Analysis

Abstract Background: Breast cancer (BC) is the most common 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 related to this pathway, can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with a short length and single-strand properties play a significant role in regulating the genes related to glutamine metabolism and 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 examined in eighty BC tissues and margin tissues. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on their gene targets. Results: In-silico studies revealed the top categories of biological processes and cellular pathways that play a critical role in metabolism reprogramming and cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (p-value= 0.02062 and fold change= -2.3801) and miR-3163 (p-value= 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup analysis did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion. Conclusion: miR-513c and miR-3163 are downregulated in BC tissues, which may act as tumor suppressors and may also be considered as potential therapeutic target for patients with BC.

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