Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells

Wong, Pooi-Fong; Jamal, Juliana; Tong, Kind-Leng; Khor, Eng-Soon; Yeap, Chia-Earn; Jong, H. G. Bungenberg de; Lee, Sui-Ting; Mustafa, Mohd Rais; AbuBakar, Sazaly

doi:10.1016/j.mvr.2017.06.002

Cited by 25 publications

(18 citation statements)

References 41 publications

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“…These findings are in agreement with our results, suggesting that patients with higher levels of hsa-miR-29b could have a greater benefit from B as both exert an anti-angiogenic effect. Although little evidence is available on the correlation between miR-20b and the angiogenic process, a recent study reported the role of hsa-miR-20b in regulating proliferation and senescence of endothelial cells, through the involvement of RBL1 [ 24 ]. We also observed that patients with a high basal level of hsa-miR-155-5p had a better outcome and that patients with a rise in the level of this type of miRNA at the first clinical evaluation (i.e., after one month of treatment) had a considerable shorter PFS and OS.…”

Section: Discussionmentioning

confidence: 99%

Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

Ulivi

Canale

Passardi

et al. 2018

IJMS

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Targeting angiogenesis in the treatment of colorectal cancer (CRC) is a common strategy, for which potential predictive biomarkers have been studied. miRNAs are small non-coding RNAs involved in several processes including the angiogenic pathway. They are very stable in biological fluids, which turns them into potential circulating biomarkers. In this study, we considered a case series of patients with metastatic (m) CRC treated with a bevacizumab (B)-based treatment, enrolled in the prospective multicentric Italian Trial in Advanced Colorectal Cancer (ITACa). We then analyzed a panel of circulating miRNAs in relation to the patient outcome. In multivariate analysis, circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p resulted in being significantly associated with progression-free survival (PFS) (p = 0.027, p = 0.034 and p = 0.039, respectively) and overall survival (OS) (p = 0.044, p = 0.024 and p = 0.032, respectively). We also observed that an increase in hsa-miR-155-5p at the first clinical evaluation was significantly associated with shorter PFS (HR 3.03 (95% CI 1.06–9.09), p = 0.040) and OS (HR 3.45 (95% CI 1.18–10.00), p = 0.024), with PFS and OS of 9.5 (95% CI 6.8–18.7) and 15.9 (95% CI 8.4–not reached), respectively, in patients with an increase ≥30% of hsa-miR-155-5p and 22.3 (95% CI 10.2–25.5) and 42.9 (24.8–not reached) months, respectively, in patients without such increase. In conclusion, our results highlight the potential usefulness of circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p in predicting the outcome of patients with mCRC treated with B. In addition, the variation of circulating hsa-miR-155-5p could also be indicative of the patient survival.

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Section: Discussionmentioning

confidence: 99%

Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

Ulivi

Canale

Passardi

et al. 2018

IJMS

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“…Lou et al (31) pointed out the unique role of miR-20b in controlling tuberculosis progression. Wong et al (32) showed that hsa-miR-20b is downregulated in tumor necrosis factor (TNF)-α-induced senescent microvascular endothelial cells. In addition, miR-20b is associated with aging and tends to be highly-expressed in the thymus of young mice (33) and upregulated in UVB-induced senescent diploid fibroblasts (34).…”

Section: Discussionmentioning

confidence: 99%

miR‑20b inhibits the senescence of human umbilical vein endothelial cells through regulating the Wnt/β‑catenin pathway via the TXNIP/NLRP3 axis

Dong

Liang

et al. 2020

Int J Mol Med

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Endothelial cell senescence is closely related to the occurrence of cardiovascular diseases and microRNAs (miRNAs/miRs) are considered as therapeutic targets for cardiovascular disease. The current study aimed to investigate the role of miR-20b in the senescence process of endothelial cells and its underlying mechanism. cell viability, proportion of senescent cells and the cell cycle were respectively determined by cell counting Kit-8, SA-β-galactosidase and flow cytometry. The relative expressions of mRNA and protein were detected by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The possible target genes and binding sites of miR-20b were predicted using Targetscan and further verified by dual luciferase reporter assay. The present study found that H 2 O 2 inhibited cell viability, caused cell cycle arrest in G1 phase, decreased miR-20b level and induced cell senescence. Moreover, high expression of miR-20b promoted cell viability and reduced H 2 O 2-induced cell senescence, whereas low expression of miR-20b produced the opposite effects. Thioredoxin interacting protein (TXNIP) was predicted as a target gene for miR-20b and knockdown of TXNIP increased cell viability, inhibited cell senescence, reduced the expression of p16, p21, TXNIP, NLR family pyrin domain containing 3 (NLRP3) and cleaved caspase-1 and reversed the promoting effects of the miR-20b inhibitor and H 2 O 2 on cell senescence. Furthermore, the knockdown of TXNIP inhibited the Wnt/β-catenin pathway. The finding reveals that high expression of miR-20b inhibits the senescence of human umbilical vein endothelial cells through regulating the Wnt/β-catenin pathway via the TXNIP/NLRP3 axis.

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“…It has been demonstrated that miR-126 overexpression activates PI3K/Akt/mTOR pathway, thereby restoring the autophagic flux and alleviating ox-LDLinduced ECs injury [25]. MiR-20b is showed to target RBL1 in the modulation of premature senescence in ECs induced by chronic exposure to TNF-α [26]. Furthermore, aberrantly expressed miRNAs have recently been reported to play a role in the regulation of ECs survival/death in the setting of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor

Qin

Shu

Long

et al. 2018

Cell Physiol Biochem

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Background/Aims: Atherosclerosis, a multifactorial chronic disease, is the main cause of death and impairment in the world. Endothelial cells (ECs) apoptosis plays a crucial role in the onset and development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a well-defined tumor suppressor in several types of cancer, while the role of miR-142-3p in ECs apoptosis and the development of atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-142-3p in ECs apoptosis during atherosclerosis and the underlying mechanism. Methods: Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT-PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay. Prediction of the binding between miR-142-3p and 3’-UTR of Rictor mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis were further analyzed in an in vivo model using ApoE^-/- mice fed with high-fat diet (HFD). Results: MiR-142-3p expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti-apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway was found to mediate the beneficial effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded the progression of atherosclerosis in the aorta of ApoE^-/- mice. Conclusions: Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic development by up-regulating the expression of Rictor and activating the Akt/eNOS signaling pathway. This indicates that miR-142-3p may be a potential target for the prevention and treatment of atherosclerosis.

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Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells

Cited by 25 publications

References 41 publications

Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer

miR‑20b inhibits the senescence of human umbilical vein endothelial cells through regulating the Wnt/β‑catenin pathway via the TXNIP/NLRP3 axis

MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor

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