scholarly journals Comprehensive analysis of lncRNA and mRNA based on expression microarray profiling reveals different characteristics of osteoarthritis between Tibetan and Han patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Junming Luo ◽  
Xiaoqin Luo ◽  
Zhili Duan ◽  
Wenbin Bai ◽  
Xiaoming Che ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathways ◽  
Critical Role ◽  
Joint Disease ◽  
Biological Processes ◽  
Expression Microarray ◽  
Chinese Han ◽  
Microarray Profiling ◽  
Trans Regulation ◽  
Mrna Expression Profiling

Abstract Background Osteoarthritis (OA) is thought to be the most prevalent chronic joint disease, especially in Tibet of China. Here, we aimed to explore the integrative lncRNA and mRNA landscape between the OA patients of Tibet and Han. Methods The lncRNA and mRNA expression microarray profiling was performed by SurePrint G3 Human Gene Expression 8x60K v2 Microarray in articular cartilage samples from OA patients of Han nationality and Tibetans, followed by GO, KEGG, and trans-regulation and cis-regulation analysis of lncRNA and mRNA. Results We found a total of 117 lncRNAs and 297 mRNAs differently expressed in the cartilage tissues of Tibetans (n = 5) comparing with those of Chinese Han (n = 3), in which 49 lncRNAs and 158 mRNAs were upregulated, and 68 lncRNAs and 139 mRNAs were downregulated. GO and KEGG analysis showed that several unreported biological processes and signaling pathways were particularly identified. LncRNA-mRNA co-expression analysis revealed a remarkable lncRNA-mRNA relationship, in which OTOA may play a critical role in the different mechanisms of the OA progression between Tibetans and Chinese Han. Conclusion This study identified different lncRNA/mRNA expression profiling between OA patients of Tibetans and Han, which were involved in many characteristic biological processes and signaling pathways.

scholarly journals Integrative Analysis of Transcriptome-Wide Association Study and mRNA Expression Profiles Identified Candidate Genes and Pathways Associated With Acute Myocardial Infarction

2021 ◽  
Vol 12 ◽  
Author(s):  
Guanzhong Chen ◽  
Liwei Liu ◽  
Huanqiang Li ◽  
Zhubin Lun ◽  
Ziling Mai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricle ◽  
Association Study ◽  
Mrna Expression ◽  
Expression Profiling ◽  
Enrichment Analysis ◽  
Biological Processes ◽  
Genetic Mechanisms ◽  
Mrna Expression Profiling

BackgroundAcute myocardial infarction (AMI), characterized by an event of myocardial necrosis, is a common cardiac emergency worldwide. However, the genetic mechanisms of AMI remain largely elusive.MethodsA genome-wide association study dataset of AMI was obtained from the CARDIoGRAMplusC4D project. A transcriptome-wide association study (TWAS) was conducted using the FUSION tool with gene expression references of the left ventricle and whole blood. Significant genes detected by TWAS were subjected to Gene Ontology (GO) enrichment analysis. Then the TWAS results of AMI were integrated with mRNA expression profiling to identify common genes and biological processes. Finally, the identified common genes were validated by RT-qPCR analysis.ResultsTWAS identified 1,050 genes for the left ventricle and 1,079 genes for whole blood. Upon comparison with the mRNA expression profile, 4 common genes were detected, including HP (PTWAS = 1.22 × 10–3, PGEO = 4.98 × 10–2); CAMP (PTWAS = 2.48 × 10–2, PGEO = 2.36 × 10–5); TNFAIP6 (PTWAS = 1.90 × 10–2, PGEO = 3.46 × 10–2); and ARG1 (PTWAS = 8.35 × 10–3, PGEO = 4.93 × 10–2). Functional enrichment analysis of the genes identified by TWAS detected multiple AMI-associated biological processes, including autophagy of mitochondrion (GO: 0000422) and mitochondrion disassembly (GO: 0061726).ConclusionThis integrative study of TWAS and mRNA expression profiling identified multiple candidate genes and biological processes for AMI. Our results may provide a fundamental clue for understanding the genetic mechanisms of AMI.

scholarly journals NF-B Signaling Pathways in Osteoarthritic Cartilage Destruction

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 734 ◽  
Author(s):  
Choi ◽  
Jo ◽  
Park ◽  
Kang ◽  
Park
Keyword(s):  
Transcription Factor ◽  
Signaling Pathways ◽  
Cartilage Destruction ◽  
Joint Disease ◽  
Nuclear Factor ◽  
Biological Processes ◽  
Comprehensive Understanding ◽  
Osteoarthritic Cartilage ◽  
Wear And Tear ◽  
Oa Chondrocytes

Osteoarthritis (OA) is a type of joint disease associated with wear and tear, inflammation, and aging. Mechanical stress along with synovial inflammation promotes the degradation of the extracellular matrix in the cartilage, leading to the breakdown of joint cartilage. The nuclear factor-kappaB (NF-B) transcription factor has long been recognized as a disease-contributing factor and, thus, has become a therapeutic target for OA. Because NF-B is a versatile and multi-functional transcription factor involved in various biological processes, a comprehensive understanding of the functions or regulation of NF-B in the OA pathology will aid in the development of targeted therapeutic strategies to protect the cartilage from OA damage and reduce the risk of potential side-effects. In this review, we discuss the roles of NF-B in OA chondrocytes and related signaling pathways, including recent findings, to better understand pathological cartilage remodeling and provide potential therapeutic targets that can interfere with NF-B signaling for OA treatment.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

scholarly journals MicroRNAs and Oxidative Stress: An Intriguing Crosstalk to Be Exploited in the Management of Type 2 Diabetes

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 802
Author(s):  
Teresa Vezza ◽  
Aranzazu M. de Marañón ◽  
Francisco Canet ◽  
Pedro Díaz-Pozo ◽  
Miguel Marti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Signaling Pathways ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Dysfunction ◽  
Non Coding Rnas ◽  
And Oxidative Stress ◽  
Molecular Crosstalk

Type 2 diabetes is a chronic disease widespread throughout the world, with significant human, social, and economic costs. Its multifactorial etiology leads to persistent hyperglycemia, impaired carbohydrate and fat metabolism, chronic inflammation, and defects in insulin secretion or insulin action, or both. Emerging evidence reveals that oxidative stress has a critical role in the development of type 2 diabetes. Overproduction of reactive oxygen species can promote an imbalance between the production and neutralization of antioxidant defence systems, thus favoring lipid accumulation, cellular stress, and the activation of cytosolic signaling pathways, and inducing β-cell dysfunction, insulin resistance, and tissue inflammation. Over the last few years, microRNAs (miRNAs) have attracted growing attention as important mediators of diverse aspects of oxidative stress. These small endogenous non-coding RNAs of 19–24 nucleotides act as negative regulators of gene expression, including the modulation of redox signaling pathways. The present review aims to provide an overview of the current knowledge concerning the molecular crosstalk that takes place between oxidative stress and microRNAs in the physiopathology of type 2 diabetes, with a special emphasis on its potential as a therapeutic target.

scholarly journals Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Camille Ternet ◽  
Christina Kiel
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Intestinal Microbiota ◽  
Critical Role ◽  
Neuroendocrine Cells ◽  
Cell Junction ◽  
Intestinal Cell ◽  
Intestinal Homeostasis ◽  
Cell Functions ◽  
The Impact

AbstractThe intestinal epithelium acts as a physical barrier that separates the intestinal microbiota from the host and is critical for preserving intestinal homeostasis. The barrier is formed by tightly linked intestinal epithelial cells (IECs) (i.e. enterocytes, goblet cells, neuroendocrine cells, tuft cells, Paneth cells, and M cells), which constantly self-renew and shed. IECs also communicate with microbiota, coordinate innate and adaptive effector cell functions. In this review, we summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions. We focus especially on intestinal stem cell proliferation, cell junction formation, remodelling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism. Recognizing the critical role of KRAS mutants in colorectal cancer, we highlight the connections of KRAS signaling pathways in coordinating these functions. Furthermore, we review the impact of KRAS colorectal cancer mutants on pathway rewiring associated with disruption and dysfunction of the normal intestinal homeostasis. Given that KRAS is still considered undruggable and the development of treatments that directly target KRAS are unlikely, we discuss the suitability of targeting pathways downstream of KRAS as well as alterations of cell extrinsic/microenvironmental factors as possible targets for modulating signaling pathways in colorectal cancer.

MicroRNA and targeted mRNA expression profiling analysis in human colorectal adenomas and adenocarcinomas

2015 ◽  
Vol 51 (3) ◽  
pp. 409-420 ◽  
Author(s):  
Charles-Henry Gattolliat ◽  
Arnaud Uguen ◽  
Marine Pesson ◽  
Kilian Trillet ◽  
Brigitte Simon ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profiling ◽  
Colorectal Adenomas ◽  
Mrna Expression Profiling ◽  
Profiling Analysis

scholarly journals The Role of EGFR/PI3K/Akt/cyclinD1 Signaling Pathway in Acquired Middle Ear Cholesteatoma

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Liu ◽  
Hongmiao Ren ◽  
Jihao Ren ◽  
Tuanfang Yin ◽  
Bing Hu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
External Auditory Canal ◽  
Cell Cycle Progression ◽  
Critical Role ◽  
Immunohistochemical Method ◽  
Cycle Progression ◽  
Middle Ear Cholesteatoma

Cholesteatoma is a benign keratinizing and hyper proliferative squamous epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of the most important cytokines which has been shown to play a critical role in cholesteatoma. In this investigation, we studied the effects of EGF on the proliferation of keratinocytes and EGF-mediated signaling pathways underlying the pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium by immunohistochemical method. Furthermore,in vitrostudies were performed to investigate EGF-induced downstream signaling pathways in primary external auditory canal keratinocytes (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma epithelium were significantly increased when compared with those of control subjects. We also demonstrated that EGF led to the activation of the EGFR/PI3K/Akt/cyclinD1 signaling pathway, which played a critical role in EGF-induced cell proliferation and cell cycle progression of EACKs. Both EGFR inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced EGFR/PI3K/Akt/cyclinD1 signaling pathway concomitantly with inhibition of cell proliferation and cell cycle progression of EACKs. Taken together, our data suggest that the EGFR/PI3K/Akt/cyclinD1 signaling pathway is active in cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper-proliferation. This study will facilitate the development of potential therapeutic targets for intratympanic drug therapy for cholesteatoma.

Gene of the month: BECN1

2014 ◽  
Vol 67 (8) ◽  
pp. 656-660 ◽  
Author(s):  
Sumit Sahni ◽  
Angelica M Merlot ◽  
Sukriti Krishan ◽  
Patric J Jansson ◽  
Des R Richardson
Keyword(s):  
Neurological Disorders ◽  
Viral Infections ◽  
Critical Role ◽  
Beclin 1 ◽  
Biological Processes ◽  
Disease States ◽  
Binding Partners ◽  
Future Drug ◽  
Cellular Components ◽  
Important Therapeutic Target

The BECN1 gene encodes the Beclin-1 protein, which is a well-established regulator of the autophagic pathway. It is a mammalian orthologue of the ATG6 gene in yeast and was one of the first identified mammalian autophagy-associated genes. Beclin-1 interacts with a number of binding partners in the cell which can lead to either activation (eg, via PI3KC3/Vps34, Ambra 1, UV radiation resistance-associated gene) or inhibition (eg, via Bcl-2, Rubicon) of the autophagic pathway. Apart from its role as a regulator of autophagy, it is also shown to effect important biological processes in the cell such as apoptosis and embryogenesis. Beclin-1 has also been implicated to play a critical role in the pathology of a variety of disease states including cancer, neurological disorders (eg, Alzheimer's disease, Parkinson's disease) and viral infections. Thus, understanding the functions of Beclin-1 and its interactions with other cellular components will aid in its development as an important therapeutic target for future drug development.

scholarly journals Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

2001 ◽  
Vol 31 (4) ◽  
pp. 1239-1246 ◽  
Author(s):  
Susanne Mathiassen ◽  
Sanne L. Lauemøller ◽  
Morten Ruhwald ◽  
Mogens H. Claesson ◽  
Søren Buus
Keyword(s):  
Mrna Expression ◽  
Tumor Immunity ◽  
Expression Profiling ◽  
Tumor Associated Antigens ◽  
Mrna Expression Profiling

scholarly journals Microarray Profiling of TGF-β1-Induced Long Non-Coding RNA Expression Patterns in Human Lung Bronchial Epithelial BEAS-2B Cells

2018 ◽  
Vol 50 (6) ◽  
pp. 2071-2085 ◽  
Author(s):  
Wentao Hu ◽  
Weiwei Pei ◽  
Lin Zhu ◽  
Jing Nie ◽  
Hailong Pei ◽  
...  
Keyword(s):  
Human Lung ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Bronchial Epithelial ◽  
Qrt Pcr ◽  
Microarray Profiling ◽  
Underlying Mechanisms ◽  
Pathway Analyses ◽  
Trans Regulation ◽  
Tgf Β1

Background/Aims: TGF-β1 mediated radiation-induced bystander effects (RIBE) have been linked with malignant transformation and tumorigenesis. However, the underlying mechanisms are not fully understood. Methods: To reveal new molecules of regulatory functions in this process, lncRNA microarray was performed to profile both lncRNA and mRNA expression patterns in human lung bronchial epithelial BEAS-2B cells treated with TGF-β1 at a concentration measured in the medium conditioned by directly irradiated BEAS-2B cells. The potential functions of the differentially expressed lncRNAs were predicted by GO and KEGG pathway analyses of their co-expressed mRNAs. Cis- and trans-regulation of the lncRNAs were analyzed and the interaction networks were constructed using Cytoscape. qRT-PCR was conducted to validate the results of microarray profiling. CCK-8 assay was employed for functional validation of 3 identified lncRNAs. Results: 224 lncRNAs were found to be dysregulated, among which 6 lncRNAs were chosen for expression validation by qRT-PCR assay. Pathway analyses showed that differentially expressed lncRNAs are highly correlated with cell proliferation, transformation, migration, etc. Trans-regulation analyses showed that the differentially expressed lncRNAs most likely participate in the pathways regulated by four transcriptional factors, FOS, STAT3, RAD21 and E2F1, which have been identified to be involved in the modulation of oncogenic transformation, cell cycle progression, genomic instability, etc. lnc-THEMIS-2 and lnc-ITGB6-4, predicted to be regulated by STAT3 and E2F1 respectively, were found to rescue the decrease of cell viability induced by TGF-β1 treatment. Conclusion: Our findings suggest that the differentially expressed lncRNAs induced by TGF-β1 play crucial roles in the oncogenic transformation and tumorigenesis, which provide a better understanding of the underlying mechanisms related to tumorigensis induced by LD/LDR radiations.

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