scholarly journals Integrated Analysis Identifies Key lncRNA-mRNA Network in Atrial Fibrillation

Author(s):  
Rou-Mu Hu ◽  
Tao Song ◽  
Zheng Liu ◽  
Xiandong Yin ◽  
Xinchun Yang

Abstract Background: Atrial fibrillation (AF), the most common cardiac arrhythmias, is associated with the risk of stroke and pronounced morbidity and mortality. The application of biomarkers in the management of AF has been grown as an interesting topic. Long non-coding RNAs (lncRNAs) have been reported to participate in the pathogenesis of cardiovascular diseases by regulating mRNA networks. Results: In this study, we firstly used two AF cohorts to identify circulating lncRNAs and mRNAs with potential diagnostic prediction value. The expression of 8,164 lncRNAs and 14,508 mRNAs were quantified in these two cohorts with lncRNA microarray. By using a stringent threshold (P < 0.01, fold change > 2.0 or < 0.5), we identified 10 lncRNAs and 7 mRNAs were significantly differentially expressed in AF in both cohorts. To further explore the function of these significantly dysregulated lncRNA and mRNA, we performed co-expression analysis by using RNA-seq data of 429 atrial appendage tissue samples. Interestingly, we found a significant lncRNA-mRNA network for 5 lncRNAs (AC109460.1, AL031123.1, MIAT, PTPRG-AS1 and ZNF815P) and 4 mRNAs (D2HGDH, SPNS1, KCND2 and TNFAIP8L3) with Pearson correlation r > 0.3 (all P < 10-8). Moreover, in silico analysis showed that the lncRNA MIAT and PTPRG-AS1 may serve as miRNA sponges to regulate D2HGDH, SPNS1, KCND2 and TNFAIP8L3.Conclusions: Our study suggested that the circulating lncRNA-mRNA network of MIAT and PTPRG-AS1 play an important role in AF and may be considerable diagnostic biomarkers. These results may contribute to the precise diagnosis and early detection of this disease.

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Quoc Thang Pham ◽  
Daiki Taniyama ◽  
Yohei Sekino ◽  
Shintaro Akabane ◽  
Takashi Babasaki ◽  
...  

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC. (199 words)


2021 ◽  
Author(s):  
Key-Hwan Lim ◽  
Sumin Yang ◽  
Sung-Hyun Kim ◽  
Jae-Yeol Joo

Abstract Background Numerous studies have been conducted on different aspects of the COVID-19 (coronavirus disease 2019) pandemic, which is caused by SARS-CoV-2, since its emergence in late 2019. Mutual relations among SARS-CoV-2 and neuro-pathophysiological phenomena are continuously being demonstrated, and several underlying diseases, such as those in the elderly, are positively correlated with susceptibility to SARS-CoV-2 infection. The expression of angiotensin converting enzyme 2 (ACE2), which is required for SARS-CoV-2 infection, was recently demonstrated to be increased in Alzheimer’s disease (AD) patients. Methods Recent preclinical studies have shown that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of SARS-CoV-2. Thus, we hypothesized that NRP1 may be upregulated in AD patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist. We used an AD mouse model that mimics AD and performed high throughput total RNA-seq with brain tissue and whole blood. For quantification of NPR1 in AD, brain tissues and blood were subjected to western blotting and RT-qPCR analysis. In silico analysis for NRP1 expression in AD patients has been performed on the human hippocampus data sets (GSE4226, GSE1297). Results Many cases of severe symptom of COVID-19 are concentrated in elderly group who have complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that Nrp1 gene was commonly overexpressed in AD model. Similar to ACE2, NRP1 protein also strongly expressed in the AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Conclusions Given that the NRP1 is highly expressed in AD, it will be important to understand and predict that NRP1 may a risk factor for SARS-CoV-2 infection in AD patients. This will support to development of potential therapeutic drug to reduce SARS-CoV-2 transmission.


2021 ◽  
Author(s):  
Key-Hwan Lim ◽  
Sumin Yang ◽  
Sung-Hyun Kim ◽  
Jae-Yeol Joo

Abstract Background Numerous studies have been conducted on different aspects of the COVID-19 (coronavirus disease 2019) pandemic, which is caused by SARS-CoV-2, since its emergence in late 2019. Mutual relations among SARS-CoV-2 and neuro-pathophysiological phenomena are continuously being demonstrated, and several underlying diseases, such as those in the elderly, are positively correlated with susceptibility to SARS-CoV-2 infection. The expression of angiotensin converting enzyme 2 (ACE2), which is required for SARS-CoV-2 infection, was recently demonstrated to be increased in Alzheimer’s disease (AD) patients.Methods Recent preclinical studies have shown that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of SARS-CoV-2. Thus, we hypothesized that NRP1 may be upregulated in AD patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist. We used an AD mouse model that mimics AD and performed high throughput total RNA-seq with brain tissue and whole blood. For quantification of NPR1 in AD, brain tissues and blood were subjected to western blotting and RT-qPCR analysis. In silico analysis for NRP1 expression in AD patients has been performed on the human hippocampus data sets (GSE4226, GSE1297).Results Many cases of severe symptom of COVID-19 are concentrated in elderly group who have complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that Nrp1 gene was commonly overexpressed in AD model. Similar to ACE2, NRP1 protein also strongly expressed in the AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression.Conclusions Given that the NRP1 is highly expressed in AD, it will be important to understand and predict that NRP1 may a risk factor for SARS-CoV-2 infection in AD patients. This will support to development of potential therapeutic drug to reduce SARS-CoV-2 transmission.


2019 ◽  
pp. 1343-1352 ◽  
Author(s):  
Bernadette Toni ◽  
Nurulhikma Md Isa ◽  
Cheng Seng Tan ◽  
Ismanizan Ismail ◽  
Zamri Zainal

CURT1 proteins in Arabidopsis thaliana have been reported to be important for inducing grana curvature. Currently, we have identified transcript encoding CURT1A from Oryza sativa cv. indica through RNA-seq analysis and characterised using heterologous system in Arabidopsis. The OsCURT1A gene shares 80% of its amino acid sequence with Arabidopsis AtCURT1A. Phylogenetic analysis revealed that the OsCURT1A is also closely related to the CURT1 proteins in other choloroplast- conatining organisms. In silico analysis of OsCURT1A promoter shows that several cis-elements related to stress are present in the 5' upstream from the coding region. Under normal conditions, there were no notable changes in the phenotype and chlorophyll a;b ratio between three Arabidopsis genotypes, which were overexpressed (35S::OsCURT1A), T-DNA insertional mutant line (atcurt1a), and Wild type (Col-0). However, overexpression of OsCURT1A under salinity condition demonstrate high chlorophyll a:b compared to Col-0, whereas, the lack of atcurt1a gene in the mutant line showed reduced chlorophyll a:b ratio. These results indicate that the OsCURT1A might have a function as salt-stress related gene, which may indirectly regulate the chlorophyll a:b ratio. Therefore, OsCURT1A can be used as a potential candidate for salinity stress tolerance in crop improvement.


2021 ◽  
Author(s):  
Javad Amini ◽  
Bahram Bibak ◽  
Amir R Afshar ◽  
Amirhossein Sahebkar

Neurodegenerative diseases (ND) are characterized by loss of function and structure of neurons. NDs like Alzheimer's disease (AD) and Parkinson's disease (PD) have high burden on the society and patients. Currently microRNAs (miRNAs) approach is growing. miRNAs express in different tissues, especially in the central neuron systems (CNS). miRNAs have a dynamic role in the CNS among this miRNAs, miR-124 significantly express in the CNS. Studies on miR-124 have shown that miR-124 improves ND. In this study, we evaluated the role of miR-124 in the ND by literature review and in silico analysis. We used Pubmed database to find miR-124 function in the Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Huntington's disease and amyotrophic lateral sclerosis. To better understand the role of miR-124 in the neurons, RNA-seq data form miR-124-deleted neuronal cells extracted from GEO database and analyzed in Galaxy platform. According literature review miR-124 attenuates inflammation and apoptosis in the ND by target NF-kb signaling pathway and regulation of BAX/BCL-2. miR-124 targets BACE1 and decreases level of Aβ. RNA-seq data showed miR-124 downregulation, an increase in chemokine gene like CCL1 and cytokine-cytokine receptor-interaction, as well as MAPK-signaling pathway. Our study shows that miR-124 can be promising therapeutic approaches to ND.


2021 ◽  
Author(s):  
Arthur C. Oliveira ◽  
Luiz A. Bovolenta ◽  
Lucas Figueiredo ◽  
James G. Patton ◽  
Danillo Pinhal

In metazoan, regulatory molecules tightly control gene expression. Among them, microRNAs (miRNAs) are key regulators of several important features, like cell proliferation, differentiation, and homeostasis. During miRNA biogenesis, the canonical strand that loads onto RISC may be switched, in a process called "arm switching". Due to the miRNA-to-target pairing peculiarities, switching events may lead to changes on the gene-targeted repertoire, promoting the modulation of a distinct set of biological routes. To understand how these events affect cell regulation, we carried out an extensive and detailed in silico analysis of RNA-seq datasets from several tissues and key developmental stages of zebrafish. We identified interesting patterns of miRNA arm switching occurrence, mainly associated with the control of protein coding genes during embryonic development. Additionally, our data shows that miRNA isoforms (isomiRs) seem to play an important role to differential arm usage. Our findings provide new insights on how such events emerge and coordinate gene expression regulation, opening perspectives for novel investigations in the area.


2021 ◽  
Author(s):  
Quoc Thang Pham ◽  
Daiki Taniyama ◽  
Yohei Sekino ◽  
Shintaro Akabane ◽  
Takashi Babasaki ◽  
...  

Abstract Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC.


2022 ◽  
Author(s):  
Tao Guo ◽  
Ran Wei ◽  
Dylan C Dean ◽  
Francis Hornicek ◽  
Zhenfeng Duan

Background: Although weak SMARCB1 expression is a known diagnostic and prognostic biomarker in several malignancies, its expression and clinical significance in osteosarcoma remain unknown. The aim of this study was to investigate SMARCB1 expression in osteosarcoma and its clinical significance with respect to chemosensitivity and prognosis. Methods: We obtained 114 specimens from 70 osteosarcoma patients to construct a tissue microarray (TMA) and assess SMARCB1 protein expression via immunohistochemistry. The mRNA expression of SMARCB1 was in silico analyzed using open-access RNA sequencing (RNA-Seq) and clinicopathological data provided by the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) project. The correlations between SMARCB1 expression and clinical features were statistically analyzed. Results: Weak SMARCB1 expression occurred in 70% of the osteosarcoma patient specimens in the tissue microarray, and significantly correlated with poor neoadjuvant response as well as shorter overall and progression-free survival. In addition, mRNA in silico analysis confirmed SMARCB1 expression correlates with chemotherapeutic response and prognosis in osteosarcoma patients. Conclusion: To our knowledge, this study is the first to analyze SMARCB1 expression in osteosarcoma. SMARCB1 may serve as a novel diagnostic and prognostic biomarker in osteosarcoma.


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