OTUD6B-AS1 Might Be a Novel Regulator of Apoptosis in Systemic Sclerosis

Takata, Miyako; Pachera, Elena; Frank-Bertoncelj, Mojca; Kozlova, Anastasiia; Jüngel, Astrid; Whitfield, Michael L.; Assassi, Shervin; Calcagni, Maurizio; Vries‐Bouwstra, Jeska de; Huizinga, Tom W J; Kurreeman, Fina; Kania, Gabriela

doi:10.3389/fimmu.2019.01100

Cited by 29 publications

(24 citation statements)

References 53 publications

(69 reference statements)

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“…OTUD6B-AS1 was first reported in systemic sclerosis (10). It is significantly downregulated in systemic sclerosis skin biopsies (10). In the field of cancer research, Wang and colleague reported OTUD6B-AS1 was downregulated in ccRCC tissue samples, and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression levels of OTUD6B-AS1 indirectly correlated with patient survival (11).…”

Section: Discussionmentioning

confidence: 99%

“…The dysregulation of lncRNA expression which acted as oncogenes or tumor-suppressor genes have great significance for the occurrence, development, metastasis, clinical stage and prognosis of thyroid cancer (7)(8)(9). OTUD6B-AS1 was first reported in systemic sclerosis (10). It is significantly downregulated in systemic sclerosis skin biopsies (10).…”

Section: Discussionmentioning

confidence: 99%

“…Under different physiological and pathological conditions, OTUD6B-AS1 is implicated in different cellular biological functions. In systemic sclerosis, OTUD6B-AS1 functions as a regulator of apoptosis (10). OTUD6B-AS1 regulates proliferation and apoptosis via cyclin D1 expression in a sense gene independent manner (10).…”

Section: Discussionmentioning

confidence: 99%

“…In systemic sclerosis, OTUD6B-AS1 functions as a regulator of apoptosis (10). OTUD6B-AS1 regulates proliferation and apoptosis via cyclin D1 expression in a sense gene independent manner (10). In tumors, OTUD6B-AS1 regulates proliferation, migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…OTUD6B-AS1 locates on chromosome 8q21.3 and has 2179 bp (NR_110439, ENST00000524003.1). OTUD6B-AS1 was initially reported as active in fibrosis in systemic sclerosis (10). It is downregulated in skin biopsies of systemic sclerosis and regulates the apoptosis of dermal fibroblasts (10).…”

Section: Introductionmentioning

confidence: 99%

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OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

et al. 2020

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Background: The long noncoding RNA (lncRNA) functions as a regulator of initiation, progression, and metastasis of thyroid carcinomas. lncRNA OTUD6B antisense RNA 1 (OTUD6B-AS1) is a tumor-suppressive noncoding RNA in clear cell renal cell carcinoma. The role of OTUD6B-AS1 in thyroid carcinomas has not been reported yet. We aim to investigate the expression and biological functions of OTUD6B-AS1 in thyroid carcinomas. Methods:The expression level of OTUD6B-AS1 was measured in 60 paired human thyroid carcinoma tissues and corresponding adjacent normal thyroid tissues. The correlations between the OTUD6B-AS1 expression levels and clinicopathological features were evaluated using the Mann-Whitney test. The effects of OTUD6B-AS1 on thyroid carcinoma cells were determined via the MTT and transwell assays. The potential targets of OTUD6B-AS1 were screened using the online programs OncomiR and StarBase 3.0, and the LncBase Predicted v.2. Luciferase reporter assay was used to confirm the interactions between OTUD6B-AS1 and its potential targets.Results: OTUD6B-AS1 was downregulated in thyroid carcinoma tissue samples. The expression of OTUD6B-AS1 correlated with tumor size, clinical stage, and lymphatic metastasis of thyroid carcinoma. Overexpression of OTUD6B-AS1 significantly decreased the viability, migration, and invasion of thyroid carcinoma cells. Online programs predicted miR-183-5p and miR-21 as potential targets of OTUD6B-AS1. Luciferase reporter assays showed miR-183-5p and miR-21 bound to OTUD6B-AS1. Moreover, overexpression of miR-183-5p and miR-21 compromised the inhibitory effects of OTUD6B-AS1 on viability, migration, and invasion of thyroid carcinoma cells.Conclusions: Taken together, our findings present in vitro evidence of lncRNA OTUD6B-AS1 as a tumor suppressor in thyroid carcinomas. OTUD6B-AS1 inhibits viability, migration, and invasion of thyroid carcinoma by targeting miR-183-5p and miR-21.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

et al. 2020

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Epigenetic Regulations in Autoimmunity and Cancer: from Basic Science to Translational Medicine

Zhao

Liu

et al. 2023

Eur J Immunol

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Epigenetics, as a discipline that aims to explain the differential expression of phenotypes arising from the same gene sequence and the heritability of epigenetic expression, has received much attention in medicine. Epigenetic mechanisms are constantly being discovered, including DNA methylation, histone modifications, noncoding RNAs and m6A. The immune system mainly achieves an immune response through the differentiation and functional expression of immune cells, in which epigenetic modification will have an important impact. Because of immune infiltration in the tumor microenvironment, immunotherapy has become a research hotspot in tumor therapy. Epigenetics plays an important role in autoimmune diseases and cancers through immunology. An increasing number of drugs targeting epigenetic mechanisms, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and drug combinations, are being evaluated in clinical trials for the treatment of various cancers (including leukemia and osteosarcoma) and autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis). This review summarizes the progress of epigenetic regulation for cancers and autoimmune diseases to date, shedding light on potential therapeutic strategies.

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Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1α signaling pathway

Liu,

Tang,

Wang

et al. 2024

Cell. Mol. Life Sci.

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Pulmonary hypertension (PAH) is a cardiopulmonary disease in which pulmonary artery pressure continues to rise, leading to right heart failure and death. Otud6b is a member of the ubiquitin family and is involved in cell proliferation, apoptosis and inflammation. The aim of this study was to understand the role and mechanism of Otud6b in PAH. C57BL/6 and Calpain-1 knockout (KO) mice were exposed to a PAH model induced by 10% oxygen. Human pulmonary artery endothelial cells (HPACEs) and human pulmonary artery smooth muscle cells (HPASMCs) were exposed to 3% oxygen to establish an in vitro model. Proteomics was used to determine the role of Otud6b and its relationship to Calpain-1/HIF-1α signaling. The increased expression of Otud6b is associated with the progression of PAH. ROtud6b activates Otud6b, induces HIF-1α activation, increases the production of ET-1 and VEGF, and further aggravates endothelial injury. Reducing Otud6b expression by tracheal infusion of siOtud6b has the opposite effect, improving hemodynamic and cardiac response to PAH, reducing the release of Calpain-1 and HIF-1α, and eliminating the pro-inflammatory and apoptotic effects of Otud6b. At the same time, we also found that blocking Calpain-1 reduced the effect of Otud6b on HIF-1α, and inhibiting HIF-1α reduced the expression of Calpain-1 and Otud6b. Our study shows that increased Otud6b expression during hypoxia promotes the development of PAH models through a positive feedback loop between HIF-1α and Calpain-1. Therefore, we use Otud6b as a biomarker of PAH severity, and regulating Otud6b expression may be an effective target for the treatment of PAH. Graphical Abstract

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OTUD6B-AS1 Might Be a Novel Regulator of Apoptosis in Systemic Sclerosis

Cited by 29 publications

References 53 publications

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

OTUD6B-AS1 Inhibits Viability, Migration, and Invasion of Thyroid Carcinoma by Targeting miR-183-5p and miR-21

Epigenetic Regulations in Autoimmunity and Cancer: from Basic Science to Translational Medicine

Otud6b induces pulmonary arterial hypertension by mediating the Calpain-1/HIF-1α signaling pathway

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