miR‐627/HMGB1/NF‐κB regulatory loop modulates TGF‐β1‐induced pulmonary fibrosis

Li, Jie; Kong, Xinyi; Jiang, Shanshan; Liao, Wenjian; Zhang, Zhihui; Song, Junfu; Liang, Ying; Zhang, Wei

doi:10.1002/jcb.27038

Cited by 20 publications

(17 citation statements)

References 36 publications

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“…16 We demonstrated that suppression of HMGB1/RAGE axis by verbascoside resulted in the attenuation of the EMT characteristics, including a reduction in Slug, Snail, and α-SMA with the increased E-cadherin. Also, HMGB1 was found to be a potential upstream regulator of TGF-β pathway, [11][12][13] which was a pivotal signaling cascade in EMT and metastasis. One of the recent studies has demonstrated that repression of TGF-β signaling may be effective to suppress bone metastasis in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

“…10 On the other hand, accumulating evidence has suggested that high-mobility group box 1 (HMGB1) is a novel mediator of EMT and capable of modulating the TGF-β-induced fibrogenesis. [11][12][13] In prostate cancer, it has been found that HMGB1 was overexpressed and may serve as a promising target for prostate cancer treatment. 14,15 Currently, it has been shown that HMGB1 promoted EMT in PC3 cells via the receptor for advanced glycation end-products (RAGE)/NF-κB signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…As a matter of fact, TGF‐β signaling is also critical to the regulation of prostate cancer microenvironment, including recruitment and activation to myofibroblasts or carcinoma‐associated fibroblasts 10 . On the other hand, accumulating evidence has suggested that high‐mobility group box 1 (HMGB1) is a novel mediator of EMT and capable of modulating the TGF‐β‐induced fibrogenesis 11‐13 . In prostate cancer, it has been found that HMGB1 was overexpressed and may serve as a promising target for prostate cancer treatment 14,15 .…”

Section: Introductionmentioning

confidence: 99%

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Verbascoside inhibits the epithelial‐mesenchymal transition of prostate cancer cells through high‐mobility group box 1/receptor for advanced glycation end‐products/TGF‐β pathway

Chen

Hsieh

et al. 2021

Environmental Toxicology

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Introduction: Prostate cancer has significant mortality and metastasis rate in the male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmacological properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the associated molecular mechanisms. Materials and Methods:The human prostate cancer cell lines, Du-145 and PC-3, were treated with various concentrations of verbascoside (0.1, 1, 10 μM) for 24 h followed by the examination of cell viability using MTT and trypan blue exclusion assays. Cell migration and invasion capacities were assessed by wound healing assay and transwell system. Western blot and immunofluorescence staining were used to detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-β)/Smad signaling, and high-mobility group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis.Results: Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-β pathway was suppressed, which was demonstrated by the diminished expression of type I and II TGF-β receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-β signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. Conclusion:Verbascoside mitigated the cell proliferation and aggressiveness of prostate cancer via downregulation of TGF-β-associated EMT progression through Chun-Hsien Wu and Chung-Hsien Chen contributed equally to this study.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Verbascoside inhibits the epithelial‐mesenchymal transition of prostate cancer cells through high‐mobility group box 1/receptor for advanced glycation end‐products/TGF‐β pathway

Chen

Hsieh

et al. 2021

Environmental Toxicology

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“…miR-627 is also reported to be a potential non-invasive diagnostic marker in gastric and breast cancer types (22,23). In pulmonary diseases, miR-627 is downregulated in patients with chronic obstructive pulmonary disease and targets the high-mobility group box protein 1 to inhibit its expression, thus improving transforming growth factor-β1-induced pulmonary fibrosis (24,25). The present results demonstrated the inhibitory effect of RP11-284F21.9 on the expression of miR-627-3p.…”

Section: Discussionmentioning

confidence: 99%

RP11‑284F21.9 promotes lung carcinoma proliferation and invasion via the regulation of miR‑627‑3p/CCAR1

Wang

Jin

et al. 2020

Oncol Rep

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Lung carcinoma is a prominent cause of mortality among patients with cancer. Previous studies have reported the vital role of long non-coding RNAs (lncRNAs) in the malignant progression of lung cancer. lncRNA RP11-284F21.9 was originally identified to be expressed in lung carcinoma, but its specific function remains unknown. Therefore, the present study aimed to elucidate the role of lncRNA RP11-284F21.9 in lung carcinoma progression. The expression of RP11-284F21.9 in lung cell lines and tissues was measured using reverse transcription-quantitative PCR. The endogenous expression of RP11-284F21.9 was silenced using RNA interference, and cell viabilities were measured with a Cell Counting Kit-8 assay. The invasion and apoptosis of cells were determined via Transwell assays and flow cytometry, respectively. The protein expression levels were measured by western blotting. An increased expression of RP11-284F21.9 was identified in both lung carcinoma tissues and cells. Knockdown of RP11-284F21.9 in lung carcinoma cells inhibited cell proliferation and invasion, but promoted cell apoptosis. The present study identified the existence of a direct interaction between RP11-284F21.9 and microRNA (miRNA/miR)-627-3p. Mechanistically, it was demonstrated that RP11-284F21.9 promoted the proliferation and invasiveness of lung carcinoma cells, in part, via the regulation of miR-627-3p. Furthermore, cell division cycle and apoptosis regulator 1 (CCAR1) was identified as a target gene of miR-627-3p. The in vivo tumor growth assay also demonstrated that the knockdown of RP11-284F21.9 suppressed tumor growth, upregulated miR-627-3p and downregulated CCAR1 in the xenograft model of nude mice. Thus, the present findings indicated the tumor promoting functions of RP11-284F21.9 in the progression of lung carcinoma, and provided a novel lncRNA/miRNA axis as a target for the management of lung cancer.

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“…Meanwhile, TGF-β1 inhibits HSC apoptosis by means of autocrine and paracrine mechanisms, induces matrix protein expression, and therefore becomes one of the most important cytokines in the process of liver fibrosis[34]. Since the promoter of the TGF-β1 activating factor tissue transglutaminase gene contains a binding site for NF-κB, the synthesis of TGF-β1 is regulated by NF-κB[35,36]. Additionally, experimental studies have shown that NF-κB can amplify the liver inflammatory reaction by enhancing the expression of some factors related to HSC activation including inflammatory factors (IL-1, TNF-α, and IL-6), cell adhesion factors, and transforming growth factors, aggravating the disease[37-40].…”

Section: Discussionmentioning

confidence: 99%

Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway

Zhang¹,

Yao²,

Zhang³

et al. 2019

WJG

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BACKGROUND The formation of liver fibrosis is mainly caused by the activation of hepatic stellate cells (HSCs) and the imbalance of extracellular matrix (ECM) production and degradation. The treatment of liver fibrosis mainly includes removing the cause, inhibiting the activation of HSCs, and inhibiting inflammation. NOD-like receptor (NLR) family, caspase activation and recruitment domain (CARD) domain containing 5/NOD27/CLR16.1 (NLRC5) is a highly conserved member of the NLR family and is involved in inflammation and immune responses by regulating various signaling pathways such as nuclear factor-κB (NF-κB) signaling. It has been found that NLRC5 plays an important role in liver fibrosis, but its specific effect and possible mechanism remain to be fully elucidated. AIM To investigate the role of NLRC5 in the activation and reversion of HSCs induced with transforming growth factor-β (TGF-β) and MDI, and to explore its relationship with liver fibrosis. METHODS A total of 24 male C57BL/6 mice were randomly divided into three groups, including normal, fibrosis, and recovery groups. Twenty-four hours after a liver fibrosis and spontaneous reversion model was established, the mice were sacrificed and pathological examination of liver tissue was performed to observe the degree of liver fibrosis in each group. LX-2 cells were cultured in vitro and treated with TGF-β1 and MDI. Real-time quantitative PCR (qPCR) and Western blot were used to analyze the expression levels of NLRC5, α-smooth muscle actin (α-SMA), and collagen type I alpha1 (Col1a1) in each group. The activity of NF-κB in each group of cells transfected with NLRC5-siRNA was detected. RESULTS Compared with the normal mice, the expression level of NLRC5 increased significantly ( P < 0.01) in the fibrosis group, but decreased significantly in the recovery group ( P < 0.01). In in vitro experiments, the content of NLRC5 was enhanced after TGF-β1 stimulation and decreased to a lower level when treated with MDI ( P < 0.01). The expression of α-SMA and Col1a1 proteins and mRNAs in TGF-β1-mediated cells was suppressed by transfection with NLRC5-siRNA ( P < 0.01). Western blot analysis showed that the expression of NF-κB p65 protein and phosphorylated IκBα (p-IκBα) was increased in the liver of mice in the fibrosis group but decreased in the recovery group ( P < 0.01), and the protein level of nuclear p65 and p-IκBα was significantly increased after treatment with NLRC5-siRNA ( P < 0.01). CONCLUSION NLRC5 may play a key role in the development and reversal of hepatic fibrosis through the NF-κB signaling pathway, and it is expected to be one of the clinical therapeutic targets.

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miR‐627/HMGB1/NF‐κB regulatory loop modulates TGF‐β1‐induced pulmonary fibrosis

Cited by 20 publications

References 36 publications

Verbascoside inhibits the epithelial‐mesenchymal transition of prostate cancer cells through high‐mobility group box 1/receptor for advanced glycation end‐products/TGF‐β pathway

Verbascoside inhibits the epithelial‐mesenchymal transition of prostate cancer cells through high‐mobility group box 1/receptor for advanced glycation end‐products/TGF‐β pathway

RP11‑284F21.9 promotes lung carcinoma proliferation and invasion via the regulation of miR‑627‑3p/CCAR1

Effect of NLRC5 on activation and reversion of hepatic stellate cells by regulating the nuclear factor-κB signaling pathway

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