Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 1
·1-10
·
IF 2.7
Shixiong Lei,Xilin Du,Kai Tan,Xiaojun He,Yejing Zhu,Shoujie Zhao,Zhenyu Yang,Gang Dou
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that cysteine rich protein 1 (CRP‑1) is dysregulated in several types of human cancer; however, its role in HCC is poorly understood. Therefore, the current study aimed to investigate the role of CRP‑1 in HCC. Western blotting and reverse transcription‑quantitative PCR results showed that CRP‑1 was upregulated in HCC cell lines. Furthermore, for in vitro experiments, CRP‑1 was knocked down and overexpressed in the HCC cell lines Hep 3B2.1‑7 and BEL‑7405, respectively. c‑Myc and proliferating cell nuclear antigen upregulation, and cleaved caspase 3 and poly(ADP‑ribose) polymerase downregulation suggested that CRP‑1 silencing could inhibit the proliferation and colony‑forming ability of HCC cells, and induce apoptosis. In addition, CRP‑1 overexpression promoted the malignant behavior of HCC cells and induced epithelial‑mesenchymal transition (EMT), as verified by E‑cadherin downregulation, and N‑cadherin and vimentin upregulation. Additionally, CRP‑1 overexpression promoted the nuclear translocation of β‑catenin, and activated the expression of cyclin D1 and matrix metalloproteinase‑7. Furthermore, inhibition of Wnt/β‑catenin signaling, following cell treatment with XAV‑939, an inhibitor of the Wnt/β‑catenin signaling pathway, abrogated the effects of CRP‑1 on enhancing the proliferation and migration of HCC cells. These findings indicated that the regulatory effect of CRP‑1 on HCC cells could be mediated by the Wnt/β‑catenin signaling pathway. Overall, CRP‑1 could promote the proliferation and migration of HCC cell lines, partially via promoting EMT and activating the Wnt/β‑catenin signaling pathway.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARCINOGENESIS
·
2023
·
IF 4.7
Han Sijia,Jin Xueying,Hu Tianyu,Chi Feng
Downregulation of ARHGAP25 was found in the tumor samples from breast cancer patients and five breast cancer cell lines. However, its precise role and molecular mechanisms in breast cancer remain completely unknown. Herein, we found that knockdown of ARHGAP25 in breast cancer cells promoted proliferation, migration and invasion of breast cancer cells. Mechanistically, ARHGAP25 silence facilitated the activation of the Wnt/β-catenin pathway and the upregulation of its downstream molecules (including c-Myc, Cyclin D1, PCNA, MMP2, MMP9, Snail, and ASCL2) by directly regulating Rac1/PAK1 in breast cancer cells. In vivo xenograft experiments indicated ARHGAP25 silence promoted tumor growth and activated the Wnt/β-catenin pathway. In contrast, overexpression of ARHGAP25 in vitro and in vivo impeded all of the above cancer properties. Intriguingly, ASCL2, a downstream target of the Wnt/β-catenin pathway, transcriptionally repressed the expression of ARHGAP25 and therefore constituted a negative feedback loop. Moreover, bioinformatics analysis indicated that ARHGAP25 is significantly correlated with tumor immune cell infiltration and the survival of patients with different immune cell subgroups in breast cancer. Collectively, our work revealed that ARHGAP25 suppressed tumor progression of breast cancer. It provides a novel insight for the treatment of breast cancer.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 1
·e14434
·
IF 3.2
Liyang Liu,Wusong Xue
Heaps of studies have verified the effects of thalidomide (THA) on colorectal cancer (CRC). Howbeit, the corresponding mechanism awaits illustration, which is the foothold of this study. Following the treatment of 0, 1.94, 7.75, or 19.36 μM THA, CRC cell viability, apoptosis, migration, and invasion were evaluated by methyl tetrazolium, flow cytometry, wound-healing, and transwell assays. Homeobox B7 (HOXB7) expression in CRC was analyzed and detected by bioinformatics analysis, quantitative real-time PCR or western blot. After the corresponding transfection or treatment with inhibitor of catenin-responsive transcription-3 (iCRT-3), abovementioned CRC cell biological behaviors as well as expression levels of HOXB7 and β-catenin were evaluated. 7.75 and 19.36 μM THA dwindled CRC cell viability, migration, and invasion, and facilitated apoptosis. HOXB7 upregulation was detected in CRC cells, which promoted the viability, migration, invasion, and β-catenin expression, and weakened the apoptosis of CRC cells. Also, HOXB7 upregulation counteracted the effects of THA on CRC cells. iCRT-3 restrained β-catenin expression, viability, migration, and invasion, whereas promoting the apoptosis of CRC cells. In addition, iCRT-3 antagonized the effects of overexpressed HOXB7 on CRC cells. THA inhibits the migration and invasion of CRC cells, which is achieved by suppressing HOXB7-mediated activation of Wnt/β-catenin signaling pathway.
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
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ruichao He,Yu Wei,Shi Yan,Jiajie Chen,Yanjun Guan,Xing Xiong,Lijing Liang,Congcong Guan,Haolin Liu,Yiben Ouyang,Junli Wang,Xiwei Peng,Jianting Ye,Jinjuan Zhao,Biqin Lai,Yu Wang,Jiang Peng,Qi Quan
A pivotal approach in engineering artificial peripheral nerve sheaths encompasses the augmentation of the regenerative microenvironment via the manipulation of Schwann cells (SCs). Our investigation employed single-cell sequencing analysis to elucidate the potential functions of Schwann cells and the Wnt pathway in facilitating peripheral nerve regeneration. In vitro studies showed that activating the Wnt signaling pathway promotes the transition to repair SCs, boosting their growth, movement, and immune functions. To better understand the peripheral nerve regeneration environment, we created a polymer scaffold using ammonization and electrospinning. The Wnt3a protein was incorporated into the polycaprolactone (PCL) electrospun fiber surface. In a rat sciatic nerve defect model, the Wnt3a-modified scaffold showed better nerve repair outcomes than traditional electrospun scaffolds. After a week, the test group showed better immune regulation and angiogenesis, with a significant increase in axon growth rate observed after 3 weeks. Three-month-long animal experiments revealed notable improvements in neuroelectrophysiology, reduced organ atrophy, and enhanced sciatic nerve recovery. In this nerve defect model, Wnt3a-modified neural scaffolds achieved repair effects.
研究领域:
生物医学工程
·
神经科学
·
组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Ziheng Yuan,Genfa Yi,Run Ma,Zhuo Wang,Jihong Hu,Wei Zhao,Ying Hu
Background Aldehyde oxidase 1 (AOX1) is associated with various pathophysiological processes, including cancer. Specifically, AOX1 has been demonstrated to have a close relationship with the progression of certain cancers. However, the expression, function, and mechanisms of action of AOX1 in gallbladder cancer (GBC) remain unclear. Methods Utilizing immunohistochemistry, the study quantified the prevalence of AOX1 within tissues of gallbladder carcinoma and those of the surrounding non-cancerous regions. In vitro assays using gallbladder carcinoma cell lines with modulated AOX1 expression levels were performed to assess the protein's role in cell proliferation, migration, and invasion. Furthermore, flow cytometry techniques were harnessed to determine the influence of AOX1 on the content of reactive oxygen species (ROS) in these cells. Additionally, the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt/β-catenin signaling pathway markersin cells with varied AOX1 expression, detected through Western blot analyses. An in vivo xenograft model involving athymic mice was implemented to explore the influence of AOX1 on gallbladder tumor growth, with Western blot analysis applied to measure EMT marker expression in the resulting tumours. Results Elevated AOX1 protein levels have been observed in gallbladder carcinoma tissues, with such upregulation linked to a negative prognostic outlook for patients. In vitro analyses demonstrate that enhanced AOX1 expression facilitates gallbladder carcinoma cell proliferation, migration, and invasion, while AOX1 suppression yields an inhibitory effect on these cellular behaviors. Western blot results reveal an inverse relationship between AOX1 and E-cadherin levels, yet was positively correlation with N-cadherin, Vimentin, and Snail within both gallbladder cancer cells and in vivo xenograft tumours. Further mechanistic investigation indicates that AOX1 elevation augments reactive oxygen species (ROS) production and initiates the Wnt/β-catenin signaling pathway in these cells. The application of N -acetylcysteine (NAC) and/or KY1797K attenuates the proliferative, migratory, and invasive enhancements imparted by AOX1 overexpression and reinforces these effects when AOX1 is silenced—achieved through ROS mitigation and the obstruction of the Wnt/β-catenin pathway. In vivo studies corroborate these findings, showing AOX1 overexpression to amplify xenograft tumor growth and mesenchymal marker expression, whereas AOX1 interference did the opposite. Conclusions The study indicates that AOX1 functions as a carcinogenic factor in gallbladder carcinoma, enhancing cell proliferation, migration, invasion, and the EMT. These effects are driven by the activation of the Wnt/β-catenin pathway mediated by reactive oxygen species (ROS). Therefore,AOX1 presents potential as a valuable prognostic and diagnostic marker as well as a target for therapeutic intervention in the gallbladder cancer.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CLINICAL SCIENCE
·
2022
·Vol. 136
·期 4
·291-307
·
IF 6.876
Liang Liping,Liu Le,Zhou Wanyan,Yang Chenghai,Mai Genghui,Li Haolin,Chen Ye
Ulcerative colitis (UC) is majorly associated with dysregulation of the dynamic cross-talk among microbial metabolites, intestinal epithelial cells, and macrophages. Several studies have reported the significant role of butyrate in host–microbiota communication. However, whether butyrate provides anti-inflammatory profiles in macrophages, thus contributing to UC intestinal mucus barrier protection, has currently remained elusive. In the current study, we found that butyrate increased mucin production and the proportion of mucin-secreting goblet cells in the colon crypt in a macrophage-dependent manner by using clodronate liposomes. Furthermore, in vivo and in vitro studies were conducted, validating that butyrate facilitates M2 macrophage polarization with the elevated expressions of CD206 and arginase-1 (Arg1). In macrophages/goblet-like LS174T cells co-culture systems, butyrate-primed M2 macrophages significantly enhanced the expression of mucin-2 (MUC2) and SPDEF (goblet cell marker genes) than butyrate alone, while blockade of WNTs secretion or ERK1/2 activation significantly decreased the beneficial effect of butyrate-primed macrophages on goblet cell function. Additionally, the adoptive transfer of butyrate-induced M2 macrophages facilitated the generation of goblet cells and mucus restoration following dextran sulfate sodium (DSS) insult. Taken together, our results revealed a novel mediator of macrophage–goblet cell cross-talk associated with the regulation of epithelial barrier integrity, implying that the microbial metabolite butyrate may serve as a candidate therapeutic target for UC.
研究领域:
免疫学
·
胃肠病学
·
微生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
·
2019
·
IF 3.485
Tao Feng,Junjie Niu,Bin Pi,Yingjie Lu,Jinning Wang,Wen Zhang,Bin Li,Huilin Yang,Xuesong Zhu
High brittleness and lack osteogenesis are two major limitations of calcium phosphate cement (CPC) in application in bone defect reconstruction. Here we prepared a composite calcium phosphate cement by mixing N-acetyl cysteine loaded silk fibroin solution with α-tricalcium phosphate. In vitro cytology experiment revealed that SF-NAC/α-TCP could significantly increase the activity of exocrine ALP and up-regulated expression of bone-related genes. However, NAC up-regulated gene expression could be significantly suppressed by DKK1. We propose that NAC functioning as osteogenic factor by activating the Wnt/β-catenin signaling pathway may be the possible mechanism of up-regulation of osteogenic genes. Bone regeneration in vivo shown in a rat femur defect was enhanced by the addition of NAC in SF/α-TCP. In addition, the combination intensity of cement-bone interface was improved. The combination SF-NAC/α-TCP might be developed into a promising tool for bone tissue repair in the clinic.
研究领域:
生物材料学
·
骨组织工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Dermatologica Sinica
·
2025
·
IF 2.2
Peng Yan,He Ling,Yang Xiaoqiong,Zhao Aijie
Background: Androgenetic alopecia (AGA), a kind of nonscarring baldness, is an androgen-dependent autosomal dominant polymorphism. Compound glycyrrhizin (CG), a compound preparation-containing glycyrrhizin, aminoacetic, and methionine, has been used to treat alopecia areata. Objectives: Our study aimed to explore the role of CG in hair regrowth in testosterone-induced AGA mouse model and the proliferation of human hair dermal papilla cells (HDPCs) and the related molecular mechanisms. Methods: The AGA mouse model was established through the injection of testosterone. The in vivo therapeutic effects of CG on AGA were assessed by detecting skin color changes, hair growth time, average hair length, and histological score. Human HDPCs after CG treatment were subjected to CCK-8 assay to evaluate cell proliferation. The impacts of CG on growth factor expression and the Wnt/β-catenin signaling in mouse dorsal skins and HDPCs were determined by undertaking western blotting, reverse transcription-quantitative polymerase chain reaction, and immunofluorescence staining. The Wnt/β-catenin pathway inhibitor XAV939 was used to validate the beneficial role of Wnt/β-catenin pathway activation in CG-mediated hair growth. Results: Our results showed that CG facilitated new hair growth and increased hair follicle numbers on the depilated dorsal area of the model mice. Furthermore, CG administration upregulated p-GSK-3β, β-catenin, cyclin D1, Axin2, LEF1, fibronectin, and survivin levels in the dorsal skins of model mice. In vitro assays revealed that CG promoted cell proliferation, elevated the mRNA levels of growth factors-related genes (insulin-like growth factors-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and hepatocyte growth factor (HGF)), and increased p-GSK-3β, β-catenin, cyclin D1, Axin2, LEF1, fibronectin, and survivin protein levels in HDPCs. Importantly, XAV939 treatment debilitated the promotion of CG on hair regrowth in model mice and human hair dermal papilla cell (HPDC) proliferation. Conclusion: The beneficial role of CG in hair regrowth in AGA mice and HDPC cell proliferation depends on the Wnt/β-catenin pathway activation and the subsequent growth factor production in hair follicles. These results imply the potential of CG in the treatment of AGA.
研究领域:
皮肤病学
·
药理学
·
分子生物学
·
细胞生物学
·
内分泌学
✓ 已验证
产品关联
DOI
高影响因子
ONCOLOGY REPORTS
·
2023
·Vol. 49
·期 3
·1-14
·
IF 4.2
Sijia Han,Xueying Jin,Tianyu Hu,Feng Chi
Breast cancer remains the most common malignancy and the leading cause of cancer‑associated mortality in women worldwide. Lysosomal protein transmembrane 5 (LAPTM5), a lysosomal membrane protein, plays an important role in several human malignancies. However, the biological functions and mechanism of LAPTM5 in breast cancer remain unclear. In the present study, the potential tumor‑promoting effect of LAPTM5 was predicted by bioinformatics analysis. LAPTM5 was highly expressed in breast cancer clinical specimens. Moreover, in vitro studies demonstrated that cell proliferation, migration and invasion, as well as the process of epithelial‑mesenchymal transition (EMT) were promoted by LAPTM5 overexpression and were suppressed by LAPTM5 downregulation in vitro. The tumor‑promoting effects of LAPTM5 were also confirmed by xenograft tumor assay in vivo. It was found that the tumor‑promoting effects of LAPTM5 were partly dependent on the activation of the Wnt/β‑catenin signaling pathway. Furthermore, dual‑luciferase and chromatin immunoprecipitation assays verified that the transcription factor forkhead box protein 3 (FOXP3) directly bound to the promoter of LAPTM5 and negatively regulated its expression. Taken together, the present findings indicated that LAPTM5, negatively regulated by FOXP3, promoted the malignant phenotypes of breast cancer through activating the Wnt/β‑catenin signaling pathway.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2020
·
IF 5.778
Qi Qin,Bingwei Yang,Zixuan Liu,Lei Xu,Erqun Song,Yang Song
Polychlorinated biphenyls (PCBs) are persistent industrial pollutants that have been linked to breast cancer progression. However, their molecular mechanism(s) are currently unclear. Our previous assessment suggested that the highly reactive PCB metabolite 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ) induces the metastasis of breast cancer. Here, our data illustrate that PCB29-pQ increases cancer stem cell (CSC) marker expression, resulting in an increase in the epithelial-mesenchymal transition (EMT) in MDA-MB-231 breast cancer cells; further, the Wnt/β-catenin pathway also becomes activated by PCB29-pQ. When the Wnt/β-catenin pathway is inhibited, the promotion of CSC properties and EMT by PCB29-pQ were accordingly reversed. In addition, the overproduction of reactive oxygen species (ROS) mediated by PCB29-pQ plays a key role in Wnt/β-catenin activation. Collectively, our current data designated the regulatory role of Wnt/β-catenin in PCB29-pQ-triggered acquisition of CSC properties and EMT.
研究领域:
毒理学
·
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Human Cell
·
2023
·
IF 4.3
Hu Lianying,Cheng Zhen,Wu Lunan,Luo Liangliang,Pan Ping,Li Shujin,Jia Qiyu,Yang Ning,Xu Bin
Osteogenic differentiation plays important roles in the pathogenesis of osteoporosis. In this study, we explored the regulatory mechanism of histone methyltransferase SET domain bifurcated 1 (SETDB1) underlying the osteogenic differentiation in osteoporosis. The common osteoporosis-related genes were retrieved from the GeneCards, CTD, and Phenolyzer databases. The enrichment analysis was conducted on the candidate osteoporosis-related genes using the PANTHER software, and the binding site between transcription factors and target genes predicted by hTFtarget. The bioinformatics analyses suggested 6 osteoporosis-related chromatin/chromatin binding protein or regulatory proteins (HDAC4, SIRT1, SETDB1, MECP2, CHD7, and DKC1). Normal and osteoporosis tissues were collected from osteoporosis patients to examine the expression of SETDB1. It was found that SETDB1 was poorly expressed in osteoporotic femoral tissues, indicating that SETDB1 might be involved in the development of osteoporosis. We induced SETDB1 overexpression/knockdown, orthodenticle homeobox 2 (OTX2) overexpression, activation of Wnt/β-catenin or BMP-Smad pathways alone or in combination in osteoblasts or ovariectomized mice. The data indicated that SETDB1 methylation regulated H3K9me3 in the OTX2 promoter region and inhibited the expression of OTX2. Besides, the BMP-Smad and Wnt/β-catenin pathways were inhibited by OTX2, thereby resulting in inhibited osteogenic differentiation. Animal experiments showed that overexpressed SETDB1 could promote the increase of calcium level and differentiation of femoral tissues. In conclusion, upregulation of SETDB1 promotes osteogenic differentiation by inhibiting OTX2 and activating the BMP-Smad and Wnt/β-catenin pathways in osteoporosis.
研究领域:
分子生物学
·
细胞生物学
·
医学遗传学
·
骨骼生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Xiaohong Xu,Vinothakumar Rajamanicham,Sujing Xu,Zhoudi Liu,Tao Yan,Guang Liang,Guilong Guo,Huiping Zhou,Yi Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking prognostic and effective therapeutic targets currently. In this study, we evaluated the toxic potential of schisandrin A (SchA), a bioactive phytochemical found in Schisandra chinensis in TNBC. The anti-cancer effect and underlying mechanism of SchA on MDA-MB-231 and BT-549 cells were determined in vitro and in xenograft mouse model. Our data show that SchA markedly inhibited the growth of TNBC cells via induction of cell cycle arrest and cell apoptosis. Moreover, over activation of Wnt signaling was observed in TNBC cells, which was significantly suppressed by the treatment of SchA. Also, SchA treatment activated ER stress in TNBC cells. Finally, we verified these inhibitory effects of SchA in the MDA-MB-231 xenograft mouse model. In conclusion, SchA effectively inhibited TNBC in preclinical models by inducing cell cycle arrest and apoptosis via regulating Wnt/ER stress signaling pathway. All of these data indicate that SchA could be a potential candidate for the treatment of TNBC.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）