scholarly journals lncRNA-RMST functioned as a SOX2 transcription co-regulator to regulate miR-1251 in the progression of Hirschsprung’s disease

2020 ◽  
Author(s):  
Lingling Zhou ◽  
Zhengke Zhi ◽  
Pingfa Chen ◽  
Zhonghong Wei ◽  
Chunxia Du ◽  
...  
Keyword(s):  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Hirschsprung Disease ◽  
Underlying Mechanism ◽  
Bioinformatic Analysis ◽  
Enteric Neurons ◽  
Intron Region ◽  
Non Coding Rnas ◽  
And Migration

ABSTRACTHirschsprung’s disease (HSCR) is a congenital disorder characterized by the absence of enteric neural crest cells (ENCCs). Non-coding RNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been authenticated as important regulators of biological functions. We conducted a microarray analysis and found lncRNA Rhabdomyosarcoma 2-associated transcript (RMST) was down-regulated in the stenotic segment of HSCR patients. MiR-1251 is transcribed from the intron region of RMST and was also low-expressed. When the expression of RMST or miR-1251 was reduced, the cell proliferation and migration were attenuated. However, RMST didn’t affect the expression of miR-1251 directly found in this study. Through bioinformatic analysis, transcription factor SOX2 was predicted to bind to the promoter region of miR-1251 which was confirmed by CHIP assay. Herein, we demonstrated that RMST exerted as a co-regulator of SOX2 to regulate the expression of miR-1251. Furtherly, AHNAK was proved to be the target gene of miR-1251 in this study. Taken together, we revealed the role of RMST/SOX2/miR-1251/AHNAK pathway in the occurrence of Hirschsprung’s disease and provided a potential therapeutic target for this disease.SUMMARY STATEMENTHirschsprung disease (HSCR) is characterized by a deficit in enteric neurons, however, the underlying mechanism remains unclear. This study revealed the role of lnc-RMST during the occurrence of HSCR.

scholarly journals Brucella-Induced Downregulation of lncRNA Gm28309 Triggers Macrophages Inflammatory Response Through the miR-3068-5p/NF-κB Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Xingmei Deng ◽  
Jia Guo ◽  
Zhihua Sun ◽  
Laizhen Liu ◽  
Tianyi Zhao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Immune Responses ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Underlying Mechanism ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Non Coding Rnas ◽  
First Time

ObjectivesThe underlying mechanism of the inflammatory response against Brucellosis caused by Brucella remains poorly understood. This study aimed to determine the role of long non-coding RNAs (lncRNAs) in regulating of inflammatory and anti-Brucella responses.Materials and methodsMicroarray analysis was performed to detect differentially expressed lncRNAs in THP-1 cells infected with an S2308 Brucella strain. The candidate lncRNAs were screened using bioinformatic analysis and siRNAs; bioinformatic prediction and luciferase reporter assay were also conducted, while inflammatory responses was assessed using RT‐qPCR, western blot, immunofluorescence, ELISA, HE, and immunohistochemistry.ResultsThe lncRNA Gm28309 was identified to be involved in regulating inflammation induced by Brucella. Gm28309, localized in the cytoplasm, was down-expressed in RAW264.7 cells infected with S2308. Overexpression of Gm28309 or inhibition of miR-3068-5p repressed p65 phosphorylation and reduced NLRP3 inflammasome and IL-1β and IL-18 secretion. Mechanistically, Gm28309 acted as a ceRNA of miR-3068-5p to activate NF-κB pathway by targeting κB-Ras2, an inhibitor of NF-κB signaling. Moreover, the number of intracellular Brucella was higher when Gm28309 was overexpressed or when miR-3068-5p or p65 was inhibited. However, these effects were reversed by the miR-3068-5p mimic.ConclusionsOur study demonstrates, for the first time, that LncRNAs are involved in regulating immune responses during Brucella infection, and Gm28309, an lncRNA, plays a crucial role in activating NF-κB/NLRP3 inflammasome signaling pathway.

Multiple 'omics'-analysis reveals the role of prostaglandin E2 in Hirschsprung's disease

2021 ◽  
Vol 164 ◽  
pp. 390-398
Author(s):  
Weibing Tang ◽  
Minjian Chen ◽  
Xuejiang Guo ◽  
Kun Zhou ◽  
Zechao Wen ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Omics Analysis

scholarly journals Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Chong Lu ◽  
Xiuhua Wang ◽  
Xiangwang Zhao ◽  
Yue Xin ◽  
Chunping Liu
Keyword(s):  
Breast Cancer ◽  
Normal Breast ◽  
Tumor Promoter ◽  
Women Health ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Migration ◽  
Breast Tissues ◽  
Long Non Coding Rna

Abstract Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

scholarly journals “Too much guts and not enough brains”: (epi)genetic mechanisms and future therapies of Hirschsprung disease — a review

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Emilie G. Jaroy ◽  
Lourdes Acosta-Jimenez ◽  
Ryo Hotta ◽  
Allan M. Goldstein ◽  
Ragnhild Emblem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Current Knowledge ◽  
Hirschsprung Disease ◽  
Gut Development ◽  
Dna And Rna ◽  
Expression Of Genes

Abstract Hirschsprung disease is a neurocristopathy, characterized by aganglionosis in the distal bowel. It is caused by failure of the enteric nervous system progenitors to migrate, proliferate, and differentiate in the gut. Development of an enteric nervous system is a tightly regulated process. Both the neural crest cells and the surrounding environment are regulated by different genes, signaling pathways, and morphogens. For this process to be successful, the timing of gene expression is crucial. Hence, alterations in expression of genes specific for the enteric nervous system may contribute to the pathogenesis of Hirschsprung’s disease. Several epigenetic mechanisms contribute to regulate gene expression, such as modifications of DNA and RNA, histone modifications, and microRNAs. Here, we review the current knowledge of epigenetic and epitranscriptomic regulation in the development of the enteric nervous system and its potential significance for the pathogenesis of Hirschsprung’s disease. We also discuss possible future therapies and how targeting epigenetic and epitranscriptomic mechanisms may open new avenues for novel treatment.

Epigenetics of scleroderma: Integrating genetic, ethnic, age, and environmental effects

2019 ◽  
Vol 4 (3) ◽  
pp. 238-250 ◽  
Author(s):  
Paula S Ramos
Keyword(s):  
Systemic Sclerosis ◽  
Epigenetic Regulation ◽  
Environmental Effects ◽  
Genetic Factors ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Epigenome Editing ◽  
Non Coding Rnas ◽  
Epigenetic Editing

Scleroderma or systemic sclerosis is thought to result from the interplay between environmental or non-genetic factors in a genetically susceptible individual. Epigenetic modifications are influenced by genetic variation and environmental exposures, and change with chronological age and between populations. Despite progress in identifying genetic, epigenetic, and environmental risk factors, the underlying mechanism of systemic sclerosis remains unclear. Since epigenetics provides the regulatory mechanism linking genetic and non-genetic factors to gene expression, understanding the role of epigenetic regulation in systemic sclerosis will elucidate how these factors interact to cause systemic sclerosis. Among the cell types under tight epigenetic control and susceptible to epigenetic dysregulation, immune cells are critically involved in early pathogenic events in the progression of fibrosis and systemic sclerosis. This review starts by summarizing the changes in DNA methylation, histone modification, and non-coding RNAs associated with systemic sclerosis. It then discusses the role of genetic, ethnic, age, and environmental effects on epigenetic regulation, with a focus on immune system dysregulation. Given the potential of epigenome editing technologies for cell reprogramming and as a therapeutic approach for durable gene regulation, this review concludes with a prospect on epigenetic editing. Although epigenomics in systemic sclerosis is in its infancy, future studies will help elucidate the regulatory mechanisms underpinning systemic sclerosis and inform the design of targeted epigenetic therapies to control its dysregulation.

scholarly journals Diagnostic Role of Calretinin in Suspicious Cases of Hirschsprung’s Disease

Cureus ◽  
2021 ◽  
Author(s):  
Sanjeev K Singh ◽  
Umesh K Gupta ◽  
Roopak Aggarwal ◽  
Rafey A Rahman ◽  
Nand K Gupta ◽  
...  
Keyword(s):  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Diagnostic Role

scholarly journals MiR-423-3p Enhances Cell Growth Through Inhibition of p21Cip1/Waf1 in Colorectal Cancer

2015 ◽  
Vol 37 (3) ◽  
pp. 1044-1054 ◽  
Author(s):  
Hong-tao Li ◽  
Hui Zhang ◽  
Yong Chen ◽  
Xian-fu Liu ◽  
Jun Qian
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rnas ◽  
And Migration

Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally, with many oncogenes and tumor suppressors involved. The miRNAs are small non-coding RNAs known to play a vital role in the pathogenesis of CRC. The miR-423-3p was reported to act as an oncogene; however, its role in CRC growth remains unknown. Methods: qPCR assay was used to detect miR-423-3p expression in CRC specimens. Cell proliferation assay and transwell assay were conducted to evaluate CRC cell proliferation and migration. Luciferase reporter assay was to identify the target gene of miR-423-3p. And tumorigenesis model was established to test the role of miR-423-3p in CRC development in vivo. Results: Here, we showed that miR-423-3p was significantly up regulated in CRC tissues and cells compared with normal tissues and cells. Overexpression of miR-423-3p promoted CRC cell proliferation via enhancing the G1/S transition phase of the cell cycle, while inhibition of miR-423-3p repressed cell growth. Further studies showed that p21Cip1/Waf1 mediated the function of miR-423-3p, and overexpression of p21Cip1/Waf1 reversed the augmented effect of miR-423-3p on cell proliferation. Importantly, all these data were validated in the tumorigenesis assay in vivo. Conclusions: In conclusion, our findings demonstrated a critical impact of miR-423-3p on CRC growth.

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