An Oxidative Stress-Related Gene Pair (CCNB1/PKD1), Competitive Endogenous RNAs, and Immune-Infiltration Patterns Potentially Regulate Intervertebral Disc Degeneration Development

Oxidative stress (OS) irreversibly affects the pathogenesis of intervertebral disc degeneration (IDD). Certain non-coding RNAs act as competitive endogenous RNAs (ceRNAs) that regulate IDD progression. Analyzing the signatures of oxidative stress-related gene (OSRG) pairs and regulatory ceRNA mechanisms and immune-infiltration patterns associated with IDD may enable researchers to distinguish IDD and reveal the underlying mechanisms. In this study, OSRGs were downloaded and identified using the Gene Expression Omnibus database. Functional-enrichment analysis revealed the involvement of oxidative stress-related pathways and processes, and a ceRNA network was generated. Differentially expressed oxidative stress-related genes (De-OSRGs) were used to construct De-OSRG pairs, which were screened, and candidate De-OSRG pairs were identified. Immune cell-related gene pairs were selected via immune-infiltration analysis. A potential long non-coding RNA–microRNA–mRNA axis was determined, and clinical values were assessed. Eighteen De-OSRGs were identified that were primarily related to intricate signal-transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. A ceRNA network consisting of 653 long non-coding RNA–microRNA links and 42 mRNA–miRNA links was constructed. Three candidate De-OSRG pairs were screened out from 13 De-OSRG pairs. The abundances of resting memory CD4+ T cells, resting dendritic cells, and CD8+ T cells differed between the control and IDD groups. CD8+ T cell infiltration correlated negatively with cyclin B1 (CCNB1) expression and positively with protein kinase D1 (PKD1) expression. CCNB1–PKD1 was the only pair that was differentially expressed in IDD, was correlated with CD8+ T cells, and displayed better predictive accuracy compared to individual genes. The PKD1–miR-20b-5p–AP000797 and CCNB1–miR-212-3p–AC079834 axes may regulate IDD. Our findings indicate that the OSRG pair CCNB1–PKD1, which regulates oxidative stress during IDD development, is a robust signature for identifying IDD. This OSRG pair and increased infiltration of CD8+ T cells, which play important roles in IDD, were functionally associated. Thus, the OSRG pair CCNB1–PKD1 is promising target for treating IDD.

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Long non‑coding RNA FAF1 promotes intervertebral disc degeneration by targeting the Erk signaling pathway

Molecular Medicine Reports ◽

10.3892/mmr.2017.8237 ◽

2017 ◽

Cited By ~ 2

Author(s):

Daguo Mi ◽

Chunyue Cai ◽

Bin Zhou ◽

Xuan Liu ◽

Peide Ma ◽

...

Keyword(s):

Intervertebral Disc ◽

Signaling Pathway ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Erk Signaling ◽

Non Coding Rna ◽

Long Non Coding Rna

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Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

International Journal of Molecular Medicine ◽

10.3892/ijmm.2020.4580 ◽

2020 ◽

Author(s):

Dongmei Gao ◽

Long Hao ◽

Zilong Zhao

Keyword(s):

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Nucleus Pulposus Cells ◽

Non Coding Rna ◽

Long Non Coding Rna

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Effects of glutamine supplementation on oxidative stress-related gene expression and antioxidant properties in rats with streptozotocin-induced type 2 diabetes

British Journal Of Nutrition ◽

10.1017/s0007114511004168 ◽

2011 ◽

Vol 107 (8) ◽

pp. 1112-1118 ◽

Cited By ~ 26

Author(s):

Pei-Hsuan Tsai ◽

Jun-Jen Liu ◽

Chui-Li Yeh ◽

Wan-Chun Chiu ◽

Sung-Ling Yeh

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Amino Acid ◽

Oxidative Damage ◽

Antioxidant Capacity ◽

Enzyme Activities ◽

Antioxidant Enzyme Activities ◽

Related Gene ◽

Gene Expressions ◽

Oxidative Stress Related Gene

There are close links among hyperglycaemia, oxidative stress and diabetic complications. Glutamine (GLN) is an amino acid with immunomodulatory properties. The present study investigated the effect of dietary GLN on oxidative stress-relative gene expressions and tissue oxidative damage in diabetes. There were one normal control (NC) and two diabetic groups in the present study. Diabetes was induced by an intraperitoneal injection of nicotinamide followed by streptozotocin (STZ). Rats in the NC group were fed a regular chow diet. In the two diabetic groups, one group (diabetes mellitus, DM) was fed a common semi-purified diet while the other group received a diet in which part of the casein was replaced by GLN (DM-GLN). GLN provided 25 % of total amino acid N. The experimental groups were fed the respective diets for 8 weeks, and then the rats were killed for further analysis. The results showed that blood thioredoxin-interacting protein (Txnip) mRNA expression in the diabetic groups was higher than that in the NC group. Compared with the DM group, the DM-GLN group had lower glutamine fructose-6-phosphate transaminase 1, a receptor of advanced glycation end products, and Txnip gene expressions in blood mononuclear cells. The total antioxidant capacity was lower and antioxidant enzyme activities were altered by the diabetic condition. GLN supplementation increased antioxidant capacity and normalised antioxidant enzyme activities. Also, the renal nitrotyrosine level and Txnip mRNA expression were lower when GLN was administered. These results suggest that dietary GLN supplementation decreases oxidative stress-related gene expression, increases the antioxidant potential and may consequently attenuate renal oxidative damage in rats with STZ-induced diabetes.

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Overexpression of long non coding RNA OR3A4 is associated with altered p38 signalling, morphological and phenotypic changes, and reduced immunogenicity in Barretts Oesophagus

10.1101/2021.05.29.21258052 ◽

2021 ◽

Author(s):

Thomas Nieto ◽

Yash Sinha ◽

Qin Qin Zhuang ◽

Mathew Coleman ◽

Joanne D Stockton ◽

...

Keyword(s):

T Cells ◽

P38 Mapk ◽

Significant Risk ◽

Oesophageal Adenocarcinoma ◽

Cellular Phenotype ◽

Over Expression ◽

Non Coding Rna ◽

P38 Mapk Inhibitor ◽

Long Non Coding Rna ◽

Mapk Inhibitor

Background: Barretts Oesophagus (BO) presents a particular pathological dilemma, in that patients who have no dysplasia within their BO experience a small but significant risk of malignant progression each year. Screening programmes have attempted to reduce the mortality from BO associated oesophageal adenocarcinoma but cannot predict which BO patients will progress to invasive malignancy. We have previously identified the long non coding RNA, OR3A4, is differentially hypomethylated in progressive BO. We aimed to understand its role in BO pathogenicity Methods: The stable BO cell line CP-A, as well as the oesophageal adenocarcinoma cells line OE-33 was transfected with a lentiviral OR3A4 over-expression vector, and underwent high resolution microscopy, immunofluorescence, RT-qPCR, RNA sequencing, and targeted drug screening with the p38-MAPK inhibitor domipramod to understand the effects of OR3A4 expression on progression. We then compared progressive vs. non-progressive BO samples using quantitative multi-fluorophore (Vectra) immunohistochemistry. Results: Over-expression of OR3A4 in CP-A lines resulted in a hyperproliferative, dysplastic cellular phenotype, with strong over-expression of MAPK and anti-apoptotic pathways at the RNA and protein level, which was sensitive to the p38-MAPK inhibitor domipramod. Vectra immunohistochemistry demonstrated that progressive BO had reduced visibility associated with a reduction in CD8+ T-cells and CD68+ macrophages and reduced CD4+ T-cells in the stomal compartment. Conclusion: The overexpression of OR3A4, which we have previously shown is associated with progressive BO leads to a proliferative dysplastic cellular phenotype associated with increased, reversible MAPK signalling and loss of immune visibility.

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Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.655157 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bei-Yan Liu ◽

Lin Li ◽

Li-Wei Bai ◽

Chang-Shui Xu

Keyword(s):

Oxidative Stress ◽

Peripheral Neuropathy ◽

Schwann Cells ◽

Diabetic Peripheral Neuropathy ◽

Beclin 1 ◽

Diabetic Mice ◽

Non Coding Rna ◽

Non Coding Rnas ◽

Long Non Coding Rna

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

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