scholarly journals Long non-coding RNA GRASLND enhances chondrogenesis via suppression of the interferon type II signaling pathway

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Nguyen PT Huynh ◽  
Catherine C Gloss ◽  
Jeremiah Lorentz ◽  
Ruhang Tang ◽  
Jonathan M Brunger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Potential ◽  
Ectopic Expression ◽  
The Novel ◽  
Type Ii ◽  
Musculoskeletal Development ◽  
Non Coding Rna ◽  
Engineered Cartilage ◽  
Interferon Type Ii ◽  
Long Non Coding Rna

The roles of long noncoding RNAs (lncRNAs) in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified the novel lncRNA GRASLND (originally named RNF144A-AS1) as a regulator of mesenchymal stem cell (MSC) chondrogenesis. GRASLND, a primate-specific lncRNA, is upregulated during MSC chondrogenesis and appears to act directly downstream of SOX9, but not TGF-β3. We showed that the silencing of GRASLND resulted in lower accumulation of cartilage-like extracellular matrix in a pellet assay, while GRASLND overexpression – either via transgene ectopic expression or by endogenous activation via CRISPR-dCas9-VP64 – significantly enhanced cartilage matrix production. GRASLND acts to inhibit IFN-γ by binding to EIF2AK2, and we further demonstrated that GRASLND exhibits a protective effect in engineered cartilage against interferon type II. Our results indicate an important role of GRASLND in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.

scholarly journals Long non-coding RNA GRASLND enhances chondrogenesis via suppression of interferon type II signaling pathway

2019 ◽  
Author(s):  
Nguyen P.T. Huynh ◽  
Catherine C. Gloss ◽  
Jeremiah Lorentz ◽  
Ruhang Tang ◽  
Jonathan M. Brunger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Mechanism ◽  
Initiation Factor ◽  
Type Ii ◽  
Non Coding Rna ◽  
Chondroprogenitor Cells ◽  
Non Coding Rnas ◽  
Interferon Type Ii ◽  
Long Non Coding Rna

AbstractLong non-coding RNAs (lncRNAs) play critical roles in regulating gene expression and cellular processes; however, their roles in musculoskeletal development, disease, and regeneration remain poorly understood. Here, we identified a novel lncRNA, Glycosaminoglycan Regulatory ASsociated Long Non-coDing RNA (GRASLND) as a regulator of mesenchymal stem cell (MSC) chondrogenesis, and we investigated its basic molecular mechanism and its potential application towards regenerative medicine. GRASLND, a primate-specific lncRNA, is upregulated during MSC chondrogenesis and appears to act directly downstream of SRY-Box 9 (SOX9), but not Transforming Growth Factor Beta 3 (TGF-β3). Utilizing the established model of pellet formation for MSC chondrogenesis, we showed that the silencing of GRASLND resulted in lower accumulation of cartilage-like extracellular matrix, while GRASLND overexpression, either via transgene ectopic expression or by endogenous activation via CRISPR, significantly enhanced cartilage matrix production. GRASLND acts to inhibit interferon gamma (IFN-γ) by binding to Eukaryotic Initiation Factor-2 Kinase EIF2AK2. We further demonstrated that GRASLND exhibits a protective effect in engineered cartilage against interferon type II across different sources of chondroprogenitor cells. Our results indicate an important role of GRASLND in regulating stem cell chondrogenesis, as well as its therapeutic potential in the treatment of cartilage-related diseases, such as osteoarthritis.SignificanceLong non-coding RNAs (lncRNAs) play critical roles in gene regulation and cellular physiology; however, the role of lncRNAs in controlling stem cell chondrogenesis remains to be determined. Here, we utilized next generation sequencing of adult stem cell chondrogenesis to identify a set of potential lncRNA candidates involved in this process. We identified lncRNA Glycosaminoglycan Regulatory ASsociated Long Non-coDing RNA (GRASLND) and characterized its molecular mechanism of action. We described a novel role of GRASLND in positive regulation of chondrogenesis via its inhibition of type II interferon. Importantly, we showed that overexpression of GRASLND augments stem cell chondrogenesis, providing a promising approach to enhancing stem cell chondrogenesis and cartilage regeneration.

scholarly journals A novel lncRNA LNC_000052 leads to the dysfunction of osteoporotic BMSCs via the miR-96-5p–PIK3R1 axis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Mingyang Li ◽  
Rong Cong ◽  
Liyu Yang ◽  
Lei Yang ◽  
Yiqi Zhang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Tissue Regeneration ◽  
Stem Cell Therapy ◽  
Therapeutic Effects ◽  
The Novel ◽  
Akt Signaling Pathway ◽  
Physiological Conditions ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Bone marrow-derived mesenchymal stem cells (BMSCs) in postmenopausal osteoporosis models exhibit loss of viability and multipotency. Identification of the differentially expressed RNAs in osteoporotic BMSCs could reveal the mechanisms underlying BMSC dysfunction under physiological conditions, which might improve stem cell therapy and tissue regeneration. In this study, we performed high-throughput RNA sequencing and showed that the novel long non-coding RNA (lncRNA) LNC_000052 and its co-expressed mRNA PIK3R1 were upregulated in osteoporotic BMSCs. Knockdown of LNC_000052 could promote BMSC proliferation, migration, osteogenesis, and inhibit apoptosis via the PI3K/Akt signaling pathway. We found that both LNC_000052 and PIK3R1 shared a miRNA target, miR-96-5p, which was downregulated in osteoporotic BMSCs. Their binding sites were confirmed by dual-luciferase assays. Downregulation of miR-96-5p could restrain the effects of LNC_000052 knockdown while upregulation of miR-96-5p together with LNC_000052 knockdown could improve the therapeutic effects of BMSCs. In summary, the LNC_000052–miR-96-5p–PIK3R1 axis led to dysfunction of osteoporotic BMSCs and might be a novel therapeutic target for stem cell therapy and tissue regeneration.

scholarly journals Author response: Long non-coding RNA GRASLND enhances chondrogenesis via suppression of the interferon type II signaling pathway

2020 ◽  
Author(s):  
Nguyen PT Huynh ◽  
Catherine C Gloss ◽  
Jeremiah Lorentz ◽  
Ruhang Tang ◽  
Jonathan M Brunger ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Author Response ◽  
Type Ii ◽  
Non Coding Rna ◽  
Interferon Type Ii ◽  
Long Non Coding Rna

scholarly journals Senescence associated long non-coding RNA 1 regulates cigarette smoke-induced senescence of type II alveolar epithelial cells through sirtuin-1 signaling

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098604
Author(s):  
Dong Yuan ◽  
Yuanshun Liu ◽  
Mengyu Li ◽  
Hongbin Zhou ◽  
Liming Cao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Sirtuin 1 ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Objective The primary aim of our study was to explore the mechanisms through which long non-coding RNA (lncRNA)-mediated sirtuin-1 (SIRT1) signaling regulates type II alveolar epithelial cell (AECII) senescence induced by a cigarette smoke-media suspension (CSM). Methods Pharmacological SIRT1 activation was induced using SRT2104 and senescence-associated lncRNA 1 (SAL-RNA1) was overexpressed. The expression of SIRT1, FOXO3a, p53, p21, MMP-9, and TIMP-1 in different groups was detected by qRT-PCR and Western blotting; the activity of SA-β gal was detected by staining; the binding of SIRT1 to FOXO3a and p53 gene transcription promoters was detected by Chip. Results We found that CSM increased AECII senescence, while SAL-RNA1 overexpression and SIRT1 activation significantly decreased levels of AECII senescence induced by CSM. Using chromatin immunoprecipitation, we found that SIRT1 bound differentially to transcriptional complexes on the FOXO3a and p53 promoters. Conclusion Our results suggested that lncRNA-SAL1-mediated SIRT1 signaling reduces senescence of AECIIs induced by CSM. These findings suggest a new therapeutic target to limit the irreversible apoptosis of lung epithelial cells in COPD patients.

scholarly journals Long non-coding RNA AGER-1 inhibits colorectal cancer progression through sponging miR-182

2020 ◽  
Vol 35 (1) ◽  
pp. 10-18 ◽  
Author(s):  
Mingzhu Lin ◽  
Yinyan Li ◽  
Jianfeng Xian ◽  
Jinbin Chen ◽  
Yingyi Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Tumor Development ◽  
Vital Role ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Colorectal Cancer Progression ◽  
And Migration ◽  
Long Non Coding Rna

Objective: Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termed lnc-AGER-1, has been discovered in cancers, and this lncRNA was reported to exert an anti-tumor effect. However, its biological mechanism remains unelucidated in colorectal cancer. Methods: A total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression of lnc-AGER-1 by the quantitative Real-time PCR (qRT-PCR), and a series of functional assays was executed to uncover the role of this lncRNA on colorectal cancer. Results: We found that the expression of lnc-AGER-1 in the tumor tissues was significantly down-regulated, while compared with adjacent normal tissues (0.0115 ± 0.0718 vs. 0.0347 ± 0.157; P < 0.0001). Also, lnc-AGER-1 was observably associated with clinical T status (r = −0.184, P = 0.024). Patients with advanced T status exerted a significantly lower level of lnc-AGER-1 than those with early T status (20.0% vs. 40.7%, P = 0.021). Over-expression of lnc-AGER-1 inhibited cell proliferation and migration efficiency, and induced cell cycle arrest at the G0/G1 phase, and promoted cell apoptosis. Further research proved that lnc-AGER-1 altered the expression of its neighbor gene, AGER, through acting as a competing endogenous RNA for miR-182 in colorectal cancer. Conclusion: lnc-AGER-1 has a suppressive role in colorectal cancer development via modulating AGER, which may serve as a target for colorectal cancer diagnosis and treatment.

Abstract 1000: The long non-coding RNA HIF1A-AS2 regulates mesenchymal glioma stem cell tumorigenicity

2016 ◽  
Author(s):  
Marco Mineo ◽  
Franz Ricklefs ◽  
Arun Rooj ◽  
Shawn M. Lyons ◽  
Pavel Ivanov ◽  
...  
Keyword(s):  
Stem Cell ◽  
Glioma Stem Cell ◽  
Non Coding Rna ◽  
Long Non Coding Rna
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