Genes & Diseases
·
2025
·
IF 9.4
Xinyue Zhao,Ruiying Liu,Zhihui Han,Zehao Li,Ling Mei,Yuyang Liu,Xueqi Fu,Yue Jin
Snail is a core inducer of epithelial-to-mesenchymal transition. Here, we show that UBR5 promotes ubiquitin-mediated degradation of Snail and regulates the progression of colorectal cancer cells through its E3 ubiquitin ligase function. UBR5 specifically binds to Snail in vitro , but not Slug, and its degradation depends on snail phosphorylation. Depletion of endogenous UBR5 causes Snail protein accumulation, epithelial-to-mesenchymal transition, and tumor invasion in colorectal cancer cells. Conversely, the overexpression of UBR5 reduces Snail protein abundance and cellular invasiveness. The activity-deficient mutant UBR5 C2768S disrupts its binding and degradation to Snail, thereby losing the ability to regulate epithelial-to-mesenchymal transition in colorectal cancer cells. UBR5 is lowly expressed in human colorectal cancer versus normal tissues, and high UBR5 levels correlate with favorable prognosis, suggesting that UBR5 sustains the epithelial state and inhibits cancer progression. These findings establish the UBR5-Snail axis as a mechanism of post-translational regulation of epithelial-to-mesenchymal transition and colorectal cancer metastasis.
研究领域:
分子生物学
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肿瘤学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
·
2020
·Vol. 42
·期 10
·2049-2058
·
IF 1.977
Song Lingyu,Wang Yan,Zhen Yunhuan,Li Dengke,He Xidong,Yang Hong,Zhang Huayang,Liu Qi
Cancer metastasis is the primary cause of death in patients diagnosed with colorectal cancer. Piperine, an active nontoxic ingredient in pepper, has potent anti-inflammatory and anti-cancer properties. However, little is known about the anti-migratory and anti-invasive effects of piperine on colorectal cancer. We demonstrated piperine inhibited the migration and invasion of colorectal cancer cells. Then, we found piperine reversed the biomarker expression of epithelial-to-mesenchymal transition (EMT), and suppressed the EMT regulator Snail. Furthermore, signal transducers and activators of transcription 3 (STAT3) was downregulated by piperine. Finally, STAT3 inhibitors were applied to observe the role of STAT3 in colorectal cancer migration, invasion and EMT. Collectively, piperine inhibits colorectal cancer migratory and invasive capacities through STAT3/Snail mediated EMT. Therefore, piperine could be applied as a possible therapeutic regimen for the prevention of colorectal cancer metastasis.
研究领域:
肿瘤学
·
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2022
·
IF 7.31
Chao Sun,Lei Wang,Dan-dan Du,Jian-bo Ji,Xiao-xia Yang,Bing-fang Yu,Peng-fei Shang,Xiu-Li Guo
Downregulated DSC2 involved in the metastasis of cancers. Unfortunately, its role on the development of gastric cancer (GC) and the potential mechanisms remain unclear. Bioinformatics analysis, Western blot, qRT-PCR, and immunohistochemistry were performed to detect the DSC2 levels of human GC and normal stomach tissues. The role of DSC2 and the downstream signaling in gastric carcinogenesis were explored by using GC specimens, GC cells with different DSC2 expression, inhibitors, and mouse metastasis models. We found that the level of DSC2 decreased significantly in GC tissues and cells. Recovered DSC2 inhibited the invasion and migration of GC cells both in culture and in xenografts. Mechanistically, DSC2 could not only decrease Snail level and nuclear BRD4 level by forming DSC2/BRD4, but also inhibit nuclear translocation of β-catenin. We concluded that DSC2 inhibited the metastasis of GC, and the underlying mechanisms were closely related to the regulation on nuclear translocation of BRD4 and β-catenin. Our results suggest that DSC2 may serve as a novel therapeutic target for GC.
研究领域:
肿瘤学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Yuan Qin,Dong Zhao,Hong-gang Zhou,Xing-hui Wang,Wei-long Zhong,Shuang Chen,Wen-guang Gu,Wei Wang,Chun-hong Zhang,Yan-rong Liu,Hui-juan Liu,Qiang Zhang,Yuan-qiang Guo,Tao Sun,Cheng Yang
Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo . Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2023
·
IF 3.8
Shouhai Wu,Meixia Yan,Junyi Liu,Yizhen Li,Ruimin Tian,Chuang Li,Lihuang Huang,Zhisheng Lu,Peng Xu,Wei Mao
Context Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN).Objective To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments.Materials and methods Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750 mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN.Results HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 ± 3.55 μg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-κB phosphorylation and inhibited α-smooth muscle actin (α-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function.Discussion and conclusions These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.
研究领域:
药理学
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分子生物学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF ONCOLOGY
·
2020
·Vol. 57
·期 1
·183-196
·
IF 3.899
Fengqi Jiang,Yaodong Chen,Shuo Ren,Zizhuo Li,Kan Sun,Yanwei Xing,Yuekun Zhu,Daxun Piao
Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2023
·
IF 3.7
Lirong Zou,Xinling Wang,Xiao Han
The retina may undergo structural and functional damage as a result of hypoxia, which could lead to permanent blindness. As competing endogenous RNAs (ceRNAs), lncRNAs are essential in eye disorders. The biological function of lncRNA MALAT 1 and its potential mechanisms in hypoxic-ischemic retinal diseases are still unknown. MALAT 1 and miR-625–3p expression alterations in hypoxia-treated RPE cells were examined using qRT-PCR. The target binding relationships between MALAT 1 and miR-625–3p, as well as between miR-625–3p and HIF-1α, were identified utilizing bioinformatics analysis and dual luciferase reporter assay. We observed that si-MALAT 1 and miR-625–3p mimic both reduced apoptosis and epithelial-mesenchymal transition (EMT) in hypoxic RPE cells, whereas si-MALAT 1 was reversed by miR-625–3p inhibitor. Further, we carried out a mechanistic investigation, and rescue assays demonstrated that MALAT 1 sponging miR-625–3p influenced HIF-1α expression and consequently took part in the NF-κB/Snail signaling pathway , which regulated apoptosis and EMT. In conclusion, our research had shown that the MALAT 1/miR-625–3p/HIF-1α axis drove the progression of hypoxic-ischemic retinal disorders and may serve as a promising predictive biomarker for their therapeutic and diagnostic targets.
研究领域:
眼科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Genes & Diseases
·
2023
·
IF 6.8
Yanran Bi,Ruiling Zheng,Jiahao Hu,Ruiqing Shi,Junfeng Shi,Yutao Wang,Peng Wang,Wenyi Jiang,Gyudong Kim,Zhiguo Liu,Xiaokun Li,Li Lin
Glioblastoma (GBM) is a malignant brain tumor that grows quickly, spreads widely, and is resistant to treatment. Fibroblast growth factor receptor (FGFR)1 is a receptor tyrosine kinase that regulates cellular processes, including proliferation, survival, migration, and differentiation. FGFR1 was predominantly expressed in GBM tissues, and FGFR1 expression was negatively correlated with overall survival. We rationally designed a novel small molecule CYY292, which exhibited a strong affinity for the FGFR1 protein in GBM cell lines in vitro . CYY292 also exerted an effect on the conserved Ser 777 residue of FGFR1 . CYY292 dose-dependently inhibited cell proliferation, epithelial–mesenchymal transition, stemness, invasion, and migration in vitro by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells, and this effect was prevented by pharmacological inhibitors and critical gene knockdown. In vivo experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547. CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models. This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292, which targets FGFR1, on downstream signaling pathways directly reducing GBM cell growth, invasion, and metastasis and thus impairing the recruitment, activation, and function of immune cells.
研究领域:
肿瘤学
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药理学
·
分子生物学
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细胞生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 43
·2004886
·
IF 16.836
Zilin Wang,Lili Liu,Wenhuan Bu,Mengdan Zheng,Nianqiang Jin,Kai Zhang,Xiaowei Xu,Ding Zhou,Bai Yang,Hongchen Sun
Skin lesions, as a relatively common clinical manifestation, not only damage the skin's barrier function, but also affect the skin's ability to feel temperature, pain and touch. However, a highly efficient method to restore the morphology and function of damaged skin remains an unmet goal. In this work, carbon dots (CDots) with excellent biocompatibility are synthesized via microwave-assisted heating ascorbic acid and polyethyleneimine. The synthesized CDots can induce the epithelial-mesenchymal transition (EMT) process by activating transforming growth factor-β/p-38 mitogen-activated kinase/Snail signaling pathway, leading to an increase of cell motility. Further, by assessing a series of in vivo wound healing assays and histological examinations, it is demonstrated that CDots can accelerate the migration of epithelial cells in the full-thickness cutaneous wounds through EMT. As a result, a rapid re-epithelialization covers the granulation tissue and epidermal barrier formed, leading to a block of the external stimuli, reduction of the inflammatory reaction and the granulation tissue area, and finally the promotion of the wound healing with fewer scars.
研究领域:
材料科学
·
生物材料
·
伤口愈合
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Biological Sciences
·
2021
·
IF 6.582
Yadong Liu,Huiyan Lv,Xingyi Li,Jiannan Liu,Song Chen,Yaodong Chen,Yinshan Jin,Ruihua An,Shiliang Yu,Zhigang Wang
Of all pathological types of renal cell cancer (RCC), clear cell renal cell carcinoma (ccRCC) has the highest incidence. Cyclovirobuxine (CVB), a triterpenoid alkaloid isolated from Buxus microphylla , exhibits antitumour activity against gastric cancer and breast cancer; however, the mechanism by which CVB inhibits ccRCC remains unclear. The aim of our study was to explore the antitumour effects of CVB on ccRCC and to elucidate its exact mechanism. Cell viability, proliferation, cell cycle distribution, apoptosis, wound healing and invasion were evaluated. Furthermore, Western blotting, immunofluorescence staining, immunohistochemical staining, and bioinformatics analyses were utilized to comprehensively probe the molecular mechanisms. The in vivo curative effect of CVB was explored using a 786-O xenograft model established in nude mice. CVB reduced cell viability, proliferation, angiogenesis, the epithelial-mesenchymal transition (EMT), migration and invasion. In addition, CVB induced cell cycle arrest in S phase and promoted apoptosis. The expression of the EMT-related transcription factor Snail was significantly downregulated by CVB via the inhibition of the AKT, STAT3 and MAPK pathways. We revealed that insulin-like growth factor binding protein 3 (IGFBP3) was the true therapeutic target of CVB. CVB exerted anti-ccRCC effects by blocking the IGFBP3-AKT/STAT3/MAPK-Snail pathway. Targeted inhibition of IGFBP3 with CVB treatment may become a promising therapeutic regimen for ccRCC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-18
·
IF 16.6
Deng Tuo,Gao Dongxiu,Song Xuemei,Zhou Zhipeng,Zhou Lixiao,Tao Maixian,Jiang Zexiu,Yang Lian,Luo Lan,Zhou Ankun,Hu Lin,Qin Hongbo,Wu Mingyi
The discovery of natural adhesion phenomena and mechanisms has advanced the development of a new generation of tissue adhesives in recent decades. In this study, we develop a natural biological adhesive from snail mucus gel, which consists a network of positively charged protein and polyanionic glycosaminoglycan. The malleable bulk adhesive matrix can adhere to wet tissue through multiple interactions. The biomaterial exhibits excellent haemostatic activity, biocompatibility and biodegradability, and it is effective in accelerating the healing of full-thickness skin wounds in both normal and diabetic male rats. Further mechanistic study shows it effectively promotes the polarization of macrophages towards the anti-inflammatory phenotype, alleviates inflammation in chronic wounds, and significantly improves epithelial regeneration and angiogenesis. Its abundant heparin-like glycosaminoglycan component is the main active ingredient. These findings provide theoretical and material insights into bio-inspired tissue adhesives and bioengineered scaffold designs.
研究领域:
生物医学工程
·
组织工程
·
伤口愈合
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jingjing Yuan,Menghan He,Jueying Yang,Kang Li,Kexiang Fan,Hang Luo,Bo Li,Yu Chen
Femur fracture becomes increasingly common due to global population aging. Intramedullary nailing, a widely used treatment for fractures, tends to damage the blood vessels in the bone marrow cavity, which causes substantial hidden bleedings. The application of hydrogels to intramedullary nail hemostasis is limited by the challenges in balancing the adhesion, mechanical strength, and toughness. Inspired by the multi-network structure of snail mucus, which offers strong adhesion in harsh environments via adaptive wet-state contact followed by tight fitting upon dehydration, we developed a dual-network carboxymethyl chitosan (CMCS)-gluconic acid δ-lactone (GDL)-Ca 2+ /polyacrylamide (PAM) (CGC/P) hydrogel. The integration of GDL with CMCS introduces hydroxyl groups to enhance the adhesion of hydrogel and regulated system pH to facilitate the formation of the dynamic CMCS-GDL-Ca 2+ physical crosslinking network. The chemically crosslinked PAM network further improves the strength and toughness of the hydrogel. As the adhesion strength of the hydrogel can be increased by up to 50.14 times upon dehydration, a stretch-winding and dehydration method is developed to coat intramedullary nails with controllable thickness, effective hemostatic properties, excellent mechanical and adhesion characteristics. In rabbit femoral intramedullary nailing surgery, this system achieves rapid hemostasis and greatly promotes osteogenesis. Our study simultaneously improves the performance regulation contradiction of hydrogel coating, providing a crucial support to promote the application of hemostatic coatings to implantations.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
骨科
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）