scholarly journals A hybrid systems biology and systems pharmacology investigation of Zingerone’s effects on reconstructed human epidermal tissues

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Elham Amjad ◽  
Babak Sokouti ◽  
Solmaz Asnaashari
Keyword(s):  
Systems Biology ◽  
Differentially Expressed Genes ◽  
Critical Role ◽  
Microarray Dataset ◽  
Skin Aging ◽  
Differentially Expressed ◽  
Systems Pharmacology ◽  
Skin Disorders ◽  
Beneficial Effects ◽  
Similar Chemical

Abstract Background As individuals live longer, elderly populations can be expected to face issues. This pattern urges researchers to investigate the aging concept further to produce successful anti-aging agents. In the current study, the effects of Zingerone (a natural compound) on epidermal tissues were analyzed using a bioinformatics approach. Methods For this purpose, we chose the GEO dataset GSE133338 to carry out the systems biology and systems pharmacology approaches, ranging from identifying the differentially expressed genes to analyzing the gene ontology, determining similar structures of Zingerone and their features (i.e., anti-oxidant, anti-inflammatory, and skin disorders), constructing the gene–chemicals network, analyzing gene–disease relationships, and validating significant genes through the evidence presented in the literature. Results The post-processing of the microarray dataset identified thirteen essential genes among control and Zingerone-treated samples. The procedure revealed various structurally similar chemical and herbal compounds with possible skin-related effects. Additionally, we studied the relationships of differentially expressed genes with skin-related diseases and validated their direct connections with skin disorders the evidence available in the literature. Also, the analysis of the microarray profiling dataset revealed the critical role of interleukins as a part of the cytokines family on skin aging progress. Conclusions Zingerone, and potentially any constituents of Zingerone (e.g., their similar compound scan functionality), can be used as therapeutic agents in managing skin disorders such as skin aging. However, the beneficial effects of Zingerone should be assessed in other models (i.e., human or animal) in future studies.

scholarly journals Integrative Systems Biology Approaches to Identify Potential Biomarkers and Pathways of Cervical Cancer

2021 ◽  
Vol 11 (5) ◽  
pp. 363
Author(s):  
Arafat Rahman Oany ◽  
Mamun Mia ◽  
Tahmina Pervin ◽  
Salem Ali Alyami ◽  
Mohammad Ali Moni
Keyword(s):  
Cervical Cancer ◽  
Systems Biology ◽  
Differentially Expressed Genes ◽  
Inflammatory Responses ◽  
Profile Analysis ◽  
Target Identification ◽  
Regulatory Genes ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Potential Biomarkers

Nowadays, cervical cancer (CC) is treated as the leading cancer among women throughout the world. Despite effective vaccination and improved surgery and treatment, CC retains its fatality rate of about half of the infected population globally. The major screening biomarkers and therapeutic target identification have now become a global concern. In the present study, we have employed systems biology approaches to retrieve the potential biomarkers and pathways from transcriptomic profiling. Initially, we have identified 76 of each up-regulated and down-regulated gene from a total of 4643 differentially expressed genes. The up-regulatory genes mainly concentrate on immune-inflammatory responses, and the down-regulatory genes are on receptor binding and gamma-glutamyltransferase. The involved pathways associated with these genes were also assessed through pathway enrichment, and we mainly focused on different cancer pathways, immunoresponse, and cell cycle pathways. After the subsequent enrichment of these genes, we have identified 12 hub genes, which play a crucial role in CC and are verified by expression profile analysis. From our study, we have found that genes LILRB2 and CYBB play crucial roles in CC, as reported here for the first time. Furthermore, the survivability of the hub genes was also assessed, and among them, finally, CXCR4 has been identified as one of the most potential differentially expressed genes that might play a vital role in the survival of CC patients. Thus, CXCR4 could be used as a prognostic and/or diagnostic biomarker and a drug target for CC.

scholarly journals Transcriptome analysis reveals the roles of stem nodes in cadmium transport to rice grain

2019 ◽  
Author(s):  
Ailing Liu ◽  
Zhibo Zhou ◽  
Yake Yi ◽  
Guanghui Chen
Keyword(s):  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Critical Role ◽  
Differentially Expressed ◽  
Rice Grain ◽  
Rna Seq ◽  
Cd Stress ◽  
Cd Accumulation ◽  
Cadmium Transport ◽  
Central Organ

Abstract Background: Node is the central organ of xylem to phloem transfer of nutrients and ions in plants. Cadmium (Cd)-induced crop pollution threatens food safety. Breeding cultivar with low Cd accumulation is a chance to resolve this universal problem. This study was performed to identify tissue specific genes involved in Cd accumulation in different rice stem nodes. Panicle node and the first node under panicle (node I) were sampled in two rice cultivars: Xiangwanxian No. 12 with low Cd accumulation and Yuzhenxiang with high Cd accumulation in the grains. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) and microRNAs. Results: Xiangwanxian No. 12 had lower Cd concentration in panicle node, node I and grain compared with Yuzhenxiang , and node Ⅰ had the highest Cd concentration in the two cultivars. RNA seq analysis identified 4,535 differentially expressed genes and 70 miRNAs between the two cultivars. Most genes ( OsIRT1 , OsNramp5, OsVIT2 , OsNRT1.5A, and OsABCC1 ) related to the “transporter activity” blocked the transport of Cd up to panicle and accumulation in grains of low Cd-accumulative cultivar. Among the genes related to “response to stimulus”, we identified OsHSP70 and OsHSFA2d/B2c in “X”, but not in “y”, were all down-regulated by Cd stimulus. The up-regulation of miRNAs ( osa-miR528 and osa-miR408 ) played a potent role in lowering Cd accumulation via down regulation of genes, such as bZIP , ERF , MYB , SnRK1 and HSPs in Xiangwanxian No. 12 cultivar. Conclusions: Both panicle node and node I of Xiangwanxian No. 12 played a key role in blocking the upward transportation of Cd, while node I played a critical role in Yuzhenxiang . Distinct expression patterns of various transporter genes such as OsNRT1.5A, OsNramp5, OsIRT1, OsVIT2 and OsABCC1 resulted in differential Cd accumulation in different nodes. Likewise, distinct expression patterns of these transporter genes are likely responsible for the low Cd accumulation in Xiangwanxian No. 12 cultivar . MiRNAs drove multiple transcription factors, such as OsbZIPs, OsERFs, OsMYBs , to play a role in stress response, which contribute to the response to Cd stress in rice.

scholarly journals Transcriptomic Systems Biology Analyses with Buparlisib (BKM120) Pan PI3K Inhibition in Canine B Cell Lymphoma (BCL): Leveraging Comparative Oncology for Cancer Therapeutics and Biomarker Discovery

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4114-4114
Author(s):  
Ravi Dashnamoorthy ◽  
Afshin Beheshti ◽  
Sarah Cass ◽  
Athena Kritharis ◽  
Kristine Burgess ◽  
...  
Keyword(s):  
Clinical Study ◽  
Systems Biology ◽  
Cancer Risk ◽  
Board Of Directors ◽  
Differentially Expressed Genes ◽  
Research Funding ◽  
Biological Pathways ◽  
Differentially Expressed ◽  
Advisory Committees ◽  
Key Genes

Abstract Background: The canine is a highly appealing model for cancer research and discovery in part due to comparable histopathological features with humans, a fully intact immune system, similar clinicopathologic features, a more comparable body size and pharmacokinetic properties than the mouse, varied breed-specific incidence rates as well as a shared environment with humans. We and others have shown prominent transcriptomic overlap of human and canine NHL (cNHL) (McDonald T et al. Onctogarget, 2018). PI3K/Akt signaling plays an important role in lymphomagenesis, which is also a promising therapeutic target. However, identification of predictive genetic aberrations of therapeutic efficacy remains elusive. We evaluated the clinical activity of the pan-PI3K inhibitor, buparlisib, in a pilot clinical study in cNHL. Methods :We enrolled and treated 10 dogs with buparlisibwho were diagnosed with BCL in an IRB and IACUC approved clinical study. Cases included 2 treatment naïve and 8 dogs with relapsed disease that had relapsed s/p CHOP (6), L' asparaginase (1) and VELCAP (1) treatment. Pet owners were consented and the study subjects received buparlisib9mg/kg orally for 28 consecutive days. Analysis for tumor response were evaluated on weekly basis through direct tumor measurement or use of x-rays. Post-therapy fine needle aspirates (FNA) were collected on Days 0, 7 and 21 to examine predictors of response to BKM120. RNA from fine need aspirate cells were isolated and the transcriptomic changes were evaluated using Canine Genome 2.0 Affymetrix Array, followed by unbiased systems biology assessment for biological pathways using Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA). We performed unbiased assessment to determine pertinent biological pathways associated with treatment response. The overall impact was used to determine the global effect on tumor progression and cancer risk based on the specific regulation of each gene. A Carcinogenic Risk Score (CRS) was calculated based on these values to determine if there is a promoted risk for cancer (positive value) or inhibitory risk for cancer (negative value) by summing the log2 fold-change values of key genes and subtracting this from the sum of log2 fold-change values of the tumor suppressors when comparing pre-treated to BKM120 treated dogs. Results: Following four weeks of BKM120 treatment, the overall response rate was 30% with 1 complete response lasting 42 days; 2 partial responses lasting 55 and 72 days; 3 stable disease; and 4 progressive disease. Mild treatment related toxicities such elevated blood glucose, thrombocytopenia and anemia, fever, nausea and lethargic symptoms, with no treatment related toxicities in 2 cases were noted. Principal Component Analysis (PCA) and hierrachical clustering analysis of differentially expressed genes show that differentially expressed genes to cluster together in all dogs during post 2 week, indicating a consistent biological activity by BKM120 in all dogs regardless of breed, prior treatment or disease status. Pathway network analysis based on differentially expressed genes predicted activation of upstream regulators associated with tumor suppression including SOX1, SOX3 and GMNN (Week 1) and CEBPA (Week 2). Analysis of "key genes" involved in multiple biological processes appeared to be associated with response of PI3K inhibitortreatment. This included down regulation of CREBBP with a Cancer Risk Score (CRS) of -0.97 and downregulation of VIM, CDH3, WNT3, WNT5B and FGFR2 with a CRS of -2.98 (Fig 1). Conclusion: Results from our pilot study in cNHL showed encouraging clinical responses with a pan-PI3K inhibitor in 3 of 10 dogs. Furthermore, our unbiased characterization of biological pathways revealed that the observed GEP changes associated with tumor suppression and they reduced the risk for cancer progression. Overall, the canine model appears to be particularly attractive model that may be leveraged for the study of clinical and biological responses to novel therapeutic oncologic agents. Disclosures Evens: Bayer: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Consultancy; Acerta: Consultancy; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics International DMC: Membership on an entity's Board of Directors or advisory committees; Tesaro: Research Funding; Janssen: Consultancy; Affimed: Consultancy.

scholarly journals Gene expression of endangered coral (Orbicella spp.) in the Flower Garden Banks National Marine Sanctuary after Hurricane Harvey

2019 ◽  
Author(s):  
Rachel M. Wright ◽  
Adrienne M.S. Correa ◽  
Lucinda A. Quigley ◽  
Sarah W. Davies
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Stress Responses ◽  
Expression Patterns ◽  
Critical Role ◽  
Sampling Time ◽  
Differentially Expressed ◽  
Tissue Loss ◽  
Time Points ◽  
East And West

AbstractAbout 160 km south of the Texas–Louisiana border, the East and West Flower Garden Banks (FGB) have maintained >50% coral cover with infrequent and minor incidents of disease or bleaching since monitoring began in the 1970s. However, a storm that generated coastal flooding, which ultimately interacted with the reef system, triggered a mortality event in 2016 that killed 2.6% of the East FGB. To capture the immediate effects of storm-driven freshwater runoff on coral and symbiont physiology, we leveraged the heavy rainfall associated with Hurricane Harvey in late August 2017 by sampling FGB corals at two times: September 2017, when salinity was reduced; and one month later when salinity had returned to typical levels (~36 ppt in October 2017). Tissue samples (N = 47) collected midday were immediately preserved for gene expression profiling from two congeneric coral species (Orbicella faveolata and Orbicella franksi) from the East and West FGB to determine the physiological consequences of storm-derived runoff. In the coral, differences between host species and sampling time points accounted for the majority of differentially expressed genes. Gene ontology enrichment for genes differentially expressed immediately after Hurricane Harvey indicated increases in cellular oxidative stress responses. Although tissue loss was not observed on FGB reefs following Hurricane Harvey, our results suggest that poor water quality following this storm caused FGB corals to experience sub-lethal stress. We also found dramatic expression differences across sampling time points in the coral’s algal symbiont, Breviolum minutum. Some of these differentially expressed genes may be involved in the symbionts’ response to changing environments, whereas a group of differentially expressed post-transcriptional RNA modification genes also suggest a critical role of post-transcriptional processing in symbiont acclimatization. In this study, we cannot disentangle the effects of reduced salinity from the collection time point, so these expression patterns may also be related to seasonality. These findings highlight the urgent need for continued monitoring of these reef systems to establish a baseline for gene expression of healthy corals in the FGB system across seasons, as well as the need for integrated solutions to manage stormwater runoff in the Gulf of Mexico.

scholarly journals Transcriptome analysis reveals the roles of stem nodes in cadmium transport to rice grain

2019 ◽  
Author(s):  
Ailing Liu ◽  
Zhibo Zhou ◽  
Yake Yi ◽  
Guanghui Chen
Keyword(s):  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Critical Role ◽  
Differentially Expressed ◽  
Rice Grain ◽  
Rna Seq ◽  
Cd Accumulation ◽  
Cadmium Transport ◽  
Upward Transport ◽  
Central Organ

Abstract Background: Node is the central organ of xylem to phloem transfer of nutrients and ions in plants. Cadmium (Cd)-induced crop pollution threatens food safety. Breeding cultivar with low Cd accumulation is a chance to resolve this universal problem. This study was performed to identify tissue specific genes involved in Cd accumulation in different rice stem nodes. Panicle node and the first node under panicle (node I) were sampled in two rice cultivars: Xiangwanxian No. 12 with low Cd accumulation and Yuzhenxiang with high Cd accumulation in the grains. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) and microRNAs. Results: Xiangwanxian No. 12 had lower Cd concentration in panicle node, node I and grain compared with Yuzhenxiang, and node Ⅰ had the highest Cd concentration in the two cultivars. RNA seq analysis identified 4,535 differentially expressed genes and 70 miRNAs between the two cultivars. Most genes (OsIRT1, OsNramp5, OsVIT2, OsNRT1.5A, and OsABCC1) related to the “transporter activity” play roles in blocking the upward transport of Cd in the low Cd-accumulative cultivar. Among the genes related to “response to stimulus”, we identified OsHSP70 and OsHSFA2d/B2c in Xiangwanxian No. 12, but not in Yuzhenxiang, were all down-regulated by Cd stimulus. The up-regulation of miRNAs (osa-miR528 and osa-miR408) played a potent role in lowering Cd accumulation via down regulation of genes, such as bZIP, ERF, MYB, SnRK1 and HSPs in Xiangwanxian No. 12 cultivar. Conclusions: Both panicle node and node I of Xiangwanxian No. 12 played a key role in blocking the upward transportation of Cd, while node I played a critical role in Yuzhenxiang. Distinct expression patterns of various transporter genes such as OsNRT1.5A, OsNramp5, OsIRT1, OsVIT2 and OsABCC1 resulted in differential Cd accumulation in different nodes. Likewise, distinct expression patterns of these transporter genes are likely responsible for the low Cd accumulation in Xiangwanxian No. 12 cultivar. MiRNAs drove multiple transcription factors, such as OsbZIPs, OsERFs, OsMYBs, to play a role in stress response, which contribute to the response to Cd stress in rice.

Identification of Differentially Expressed Genes in the Rituximab- Resistant Clone (Ramos RR1) Compared to Wildtype Sensitive Ramos: Therapeutic Implications in Rituximab-Resistance

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3770-3770
Author(s):  
Stavroula Baritaki ◽  
Jose Rodriguez ◽  
Gustavo Helguera ◽  
Melisa Martinez-Paniagua ◽  
Mario Vega ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Differentially Expressed Genes ◽  
Tyrosine Phosphatase ◽  
Critical Role ◽  
Differentially Expressed ◽  
Gene Products ◽  
Therapeutic Implications ◽  
Growth Promoting ◽  
Survival Signaling ◽  
Tyrosyl Phosphorylation

Abstract Treatment of patients with relapsed or refractory B-NHL with rituximab alone or in combination with CHOP has resulted in significant clinical response. However, a subset of patients does not initially respond or develops resistance to such therapies. The mechanism underlying rituximab resistance is not fully understood. We have explored a possible mechanism by generating in the laboratory rituximab resistant clones (Ramos RR, Daudi RR, and 2F7 RR) and reported that the clones, unlike the parental wild type (wt), no longer respond to rituximab-induced cell signaling and chemo- immuno-sensitization. For instance, we have demonstrated that the resistant clones exhibit hyperactivation of cell survival signaling pathways, such as the NF-kB and Raf-1/MEK/ERK pathways, and overexpress several anti-apoptotic gene products that regulate apoptosis (Jazirehi et al., Cancer Research 67:1270–1281, 2007). To further characterize the molecular basis of rituximab-resistance, we analyzed the gene expression profile of Ramos and Ramos RR1 using oligonucleotide microarrays. There were only a few genes that were significantly modified and we have focused on such genes for analysis. First, we analyzed genes that were present in Ramos RR1 and silenced in wtRamos, namely, KIAA0738, DHTKDU1, PTPRO, REG3A, and ATXN10. Analysis of some of these gene products revealed their possible role in the regulation of resistance. For instance, REG3A, regenerating islet-derived 3α, a growth promoting lectin, has been reported to be involved in various biological functions including proliferation and resistance to apoptosis and silenced by hypermethylation. This suggests that REG3A expression in Ramos RR1 may be due to inhibition of hypermethylation. Another gene product silenced in wtRamos but expressed in Ramos RR1 is the protein tyrosine phosphatase receptor type O (PTPRO), which is known to be hypermethylated in response to rituximab therapy. Overexpression of PTPRO inhibits BCR-triggered syk tyrosyl phosphorylation and cell signaling. Hence, rituximab has been reported to trigger cells through the association of BCR with CD20 on the membrane. Second, we analyzed differentially expressed genes between Ramos RR1 and wtRamos. Two gene products, MAP3K14, and ACN9 were most overexpressed, whereas PAM, SDCCAG33, and NPAS4 were most downregulated in Ramos RR1. Overexpression of MAP3K14 (NIK) is in agreement with the hyperactivated state of Ramos RR1, and in addition to our findings of hyperactivation of the canonical NF-κB pathway, would suggest that the non-canonical pathway is also activated. Hyperactivation of NIK in Ramos RR1 may be due to its stabilization by NF-κB-dependent degradation of TRAF-3 and our findings are consistent with NIK overexpression in other blood malignancies. PAM (phosphatydyl-glycine α amidating monooxygenase) is an enzyme that has been reported to play a critical role in an autocrine pathway promoting proliferation. Its downregulation in Ramos RR1 suggests PAM-independence. Findings will be presented on the validation and roles of the above gene products in the regulation of rituximab resistance and approaches to target such gene products to reverse resistance.

scholarly journals Recent Trends of Sunscreen Cosmetic: An Update Review

Cosmetics ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 64 ◽  
Author(s):  
Ngoc ◽  
Tran ◽  
Moon ◽  
Chae ◽  
Park ◽  
...  
Keyword(s):  
Vitamin D ◽  
Prolonged Exposure ◽  
Skin Aging ◽  
Environment Pollution ◽  
Uv Filters ◽  
Skin Disorders ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Emulsion Gel ◽  
Recent Trends

Ultraviolet (UV) radiation has been demonstrated to cause skin disorders, including sunburn and relative symptoms of prolonged exposure. It has been reported that sunscreens have beneficial effects in reducing the incidence of skin disorders (sunburn, skin aging, and immunosuppression) through their ability to absorb, reflect, and scatter UV. Many commercial products have recently been manufactured from not only usual organic and inorganic UV filters, but also hybrid and botanical ingredients using typical formulations (emulsion, gel, aerosol, and stick). Particularly, these products have been supplemented with several preeminent properties to protect against the negative effects of not only UVB, but also UVA. However, the use of sunscreen has faced many challenges, including inducing photoallergic dermatitis, environment pollution, and deficiency of vitamin D production. Therefore, consumers should efficiently apply suitable products to improve sun protection. as well as to avoid the side effects of sunscreen.

scholarly journals miR-146b-5p Plays a Critical Role in the Regulation of Autophagy in ∆per Brucella melitensis-Infected RAW264.7 Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Jiao Hanwei ◽  
Xin Nie ◽  
Huapei Zhu ◽  
Baobao Li ◽  
Feng Pang ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
High Throughput ◽  
Brucella Melitensis ◽  
Critical Role ◽  
Differentially Expressed ◽  
Raw264.7 Cells ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
Protective Antibodies ◽  
Molecular Patterns

Brucella-caused brucellosis is one of the most widespread worldwide zoonoses. Lipopolysaccharide (LPS) of Brucella, which functions as pathogen-associated molecular patterns (PAMPs), is an important virulence factor that elicits protective antibodies. Per of B. melitensis is involved in the biosynthesis of the O-side chain of LPS. Autophagy is a crucial element of the innate immune response against intracellular pathogens including Brucella. In this study, we observed that autophagy was inhibited in RAW264.7 cells infected with Brucella melitensis ∆per. And, a high-throughput array-based screen and qRT-PCR validation were performed to identify the differentially expressed miRNAs in RAW264.7 cells infected with B. melitensis M5-90 ∆per. The results suggested that mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-146b-5p, and mmu-miR-3473a were upregulated and mmu-miR-30c-5p was downregulated. During B. melitensis M5-90 ∆per infection, the increased expression of miR-146b-5p inhibited the autophagy activation in RAW264.7 cells. Using a bioinformatics approach, Tbc1d14 was predicted to be a potential target of miR-146b-5p. The results of a luciferase reporter assay indicated that miR-146b-5p directly targeted the 3′-UTR of Tbc1d14, and the interaction between miR-146b-5p and the 3′-UTR of Tbc1d14 was sequence-specific. High-throughput RNA-Seq-based screening was performed to identify differentially expressed genes in Tbc1d14-expressing RAW264.7 cells, and these were validated by qRT-PCR. Among the differentially expressed genes, four autophagy associated genes, IFNγ-inducible p47 GTPase 1 (IIGP1), nuclear receptor binding protein 2 (Nrbp2), transformation related protein 53 inducible nuclear protein 1 (Trp53inp1), and immunity-related GTPase family M member 1 (Irgm1), were obtained. Our findings provide important insights into the functional mechanism of LPS of B. melitensis.

scholarly journals Bioinformatics analysis of differentially expressed genes and their potentially interacting miRNAs in oral lichen planus

2021 ◽  
Author(s):  
Churen Zhang ◽  
Ruoran Sun
Keyword(s):  
Lichen Planus ◽  
Differentially Expressed Genes ◽  
Oral Lichen Planus ◽  
Kegg Pathway ◽  
Microarray Dataset ◽  
Epidermal Differentiation ◽  
Differentially Expressed ◽  
Ppi Network ◽  
Hub Genes ◽  
Oral Lichen

Abstract Background Oral lichen planus (OLP) was a common oral mucosal disease. However, the etiology and pathogenesis of OLP were still limited. This research was designed to identify the differentially expressed genes and relative miRNAs in OLP. Methods and Results The OLP microarray dataset (GSE52130) was download from the Gene Expression Omnibus (GEO) database. R software was used to identify differentially expressed genes between the OLP samples and normal oral mucosa. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway conducted. Protein–protein interaction (PPI) network analysis was performed in the STRING database. CytoHubba in the Cytoscape software was applied to determining the top 10 hub genes, whose relative miRNA was identified through RNA Interactome Database. Overall, 627 DEGs was identified in OLP samples, including 351 highly expressed genes and 276 lowly expressed genes. GO analysis indicated that the epidermal differentiation was mostly enriched. For the KEGG pathway, the DEGs in OLP samples were mostly involved in Staphylococcus aureus infection. Top 10 hub genes were identified from the PPI network. The miRNA (hsa-miR-98-5p) was regarded as the mostly possible miRNA involved in OLP. Conclusions The epidermal differentiation complex and functional miRNAs (hsa-miR-98-5p, hsa-let-7e-5p, hsa-let-7f-5p) were potential biomarkers of OLP

scholarly journals Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment

2020 ◽  
Author(s):  
Shatovisha Dey ◽  
Sheng Liu ◽  
Tricia D Factora ◽  
Solaema Taleb ◽  
Primavera Riverahernandez ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Stellate Cell ◽  
Critical Role ◽  
Differentially Expressed ◽  
Pancreatic Stellate Cells ◽  
Ductal Adenocarcinoma ◽  
Pancreatic Stellate Cell ◽  
Western Blots ◽  
Incidence And Mortality

Abstract BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms of malignancies with a nearly equal incidence and mortality rates in patients. Pancreatic stellate cells (PSCs) are critical players in PDAC microenvironment to promote the aggressiveness and pathogenesis of the disease. Dysregulation of microRNAs (miRNAs) have been shown to play a significant role in progression of PDAC. Earlier, we observed a PSC-specific downregulation of miR-29a in PDAC pancreas, however, the mechanism of action of the molecule in PSCs is still to be elucidated. The current study aims to clarify the regulation of miR-29a in PSCs and identifies functionally important downstream targets that contribute to tumorigenic activities during PDAC progression. MethodsIn this study, using RNAseq approach, we performed transcriptome analysis of paired miR-29a overexpressing hPSC cells and controls. Enrichment analysis was performed with the identified differentially expressed genes (DEGs). miR-29a targets in the dataset were identified, which were utilized to create network interactions. Western blots were performed with the top candidate miR-29a targets in hPSC cells transfected with miR-29a mimic or scramble control. ResultsRNAseq analysis identified 202 differentially expressed genes, which included 19 downregulated direct miR-29a targets. Translational repression of eight key pro-tumorigenic and -fibrotic targets namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 and ADAMTS2 by miR-29a was observed in PSCs. Using pathway analysis, we find that miR-29a modulates effectors of IGF-1-p53 signaling in PSCs that may hinder carcinogenesis. We further observe a regulatory role of the molecule in pathways associated with PDAC ECM remodeling and tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions and collagen biosynthesis. ConclusionsTogether, our study presents a comprehensive understanding of miR-29a regulation of PSCs, and identifies essential pathways associated with PSC-mediated PDAC pathogenesis. The findings suggest an anti-tumorigenic role of miR-29a in the context of PSC-tumor cell crosstalk and advocates for the potential of the molecule in PDAC targeted therapies.

Sign in / Sign up

Export Citation Format

Share Document