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.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BONE
·
2022
·
IF 4.626
Senxin Cai,Yuchun Zou,Yong Zhao,Hanyu Lin,Dali Zheng,Linyu Xu,Youguang Lu
Aims Mechanical stress overload in the temporomandibular joint (TMJ) is an important cause of TMJ osteoarthritis (TMJOA). Whether secreted frizzled-related proteins (SFRPs) play important roles in the development of mechanical stress-induced TMJOA remains controversial. In this study, we investigated the roles of the Wnt/β-catenin signaling and SFRPs in the progression of mechanical stress-induced TMJOA. Methods We investigated the progression of mechanical stress-induced TMJOA using an in vivo model via modified increased occlusal vertical dimension (iOVD) malocclusion and an in vitro model in which isolated chondrocytes were subjected to mechanical stress. The effects of inhibition of Wnt/β-catenin signal on TMJOA induced by mechanical stress were studied by in vitro drug added and in vivo intra-articular injection of XAV-939. TMJOA progression, Wnt/β-catenin signaling and SFRPs was assessed by Cone beam computed tomography (CBCT) analysis, histochemical and immunohistochemical (IHC) staining, quantitative real-time PCR (qRT–PCR), Western blotting (WB), and immunofluorescence (IF) staining. Results Our in vivo results showed that iOVD-induced mechanical stress in the TMJ disrupted mandible growth, induced OA-like changes in TMJ cartilage, and increased OA-related cytokine expression. In addition, iOVD activated Wnt/β-catenin signaling and suppressed Sfrp1 , Sfrp3 , and Sfrp4 expression in condylar cartilage. Moreover, our in vitro study showed that stress disrupted homeostasis , activated Wnt/β-catenin signaling and inhibited SFRP3 and SFRP4 expression in chondrocytes. Suppression of Wnt/β-catenin signaling with XAV-939 promoted SFRP3 and SFRP4 expression and rescued mechanical stress-induced cartilage degeneration in vivo and in vitro. Conclusions Our work suggests that mechanical stress reduces SFRPs expression both in vivo and in vitro and promotes TMJOA via Wnt/β-catenin signaling. Suppression of Wnt/β-catenin signaling promotes SFRPs expression, especially SFRP3 and SFRP4 expression, and rescues mechanical stress-induced cartilage degeneration. Wnt/β-catenin signaling and SFRPs may represent potential therapeutic targets for TMJOA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Translation
·
2022
·
IF 4.889
Feng-wei Zhang,Li-yang Peng,Chuan-Jian Shi,Jian-chi Li,Feng-xiang Pang,Wei-ming Fu,Xiao-hua Pan,Jin-fang Zhang
Background Osteosarcoma (OS) is a common type of malignant bone tumor in adolescents with high risk of metastasis. However, the clinical management still remains unsatisfactory. Traditional Chinese medicine (TCM) has been widely considered as an alternative treatment, and their extracts have proved to possess great potential for drug discovery. Baicalein (BA), the active pharmaceutical ingredient of rhizoma coptidis , was proved to have anti-tumor properties in OS, but the mechanism remains poorly understood. Methods The potential anti-cancer effects on cell growth, cell cycle, apoptosis and migration were examined in OS cells. Moreover, the lncRNA-Neighboring Enhancer of FOXA2 (lncRNA-NEF) and Wnt/β-catenin signaling were detected by qPCR and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using a xenograft mice model. Results In the present study, BA was found to significantly suppress tumor growth in vitro and in vivo. And it was also found to inhibit the invasion and metastasis as well. As for the mechanism investigation, lncRNA-NEF was obviously upregulated by BA in OS cells, and thus induced the inactivation of Wnt/β-catenin signaling. Moreover, lncRNA-NEF knockdown partially reversed the BA-induced anti-cancer activities; and successfully compensated the suppressive effect on Wnt/β-catenin signaling. We therefore suggested that BA induced the inactivation of Wnt/β-catenin signaling through promoting lncRNA-NEF expression. Conclusions In conclude, our results demonstrated that BA suppressed tumor growth and metastasis in vitro and in vivo through an lncRNA-NEF driven Wnt/β-catenin regulatory axis, in which lncRNA-NEF was upregulated by BA, and thus induced the inactivation of Wnt/β-catenin signaling. The Translational potential of this article The findings derived from this study validates the anti-cancer activity of BA in OS and provides a novel underlying mechanism, which suggest that BA may be a potential candidate to develop the effective drug for OS patients.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Runxiao Lv,Lili Du,Lunhao Bai
Osteoarthritis (OA) is a chronic joint disease characterized by the progressive degradation of articular cartilage. In this study, as determined by histological staining, the cartilage surface of the OA rats was damaged, defective and broken, and chondrocytes and proteoglycan were reduced. While moderate physical exercise showed protective effects on the cartilage. Besides, RNA-seq was performed to select a target protein and RNF125 (an E3 ubiquitin ligase) was decreased in the cartilage tissues of OA rats and increased after physiological exercise. However, the precise role of RNF125 in OA is still unknown. This work aimed to investigate the involvement and underlying mechanism of RNF125 in OA pathogenesis. Our results defined that adenovirus-mediated overexpression of RNF125 inhibited the degradation of extracellular matrix of chondrocytes induced by IL-1β, as revealed by increased chondrocyte viability, upregulated COL2A1 and ACAN levels, and downregulated MMP1, MMP13 and ADAMTS5 levels, which was abrogated by NR4A2 knockdown. In vivo, RNF125 relieved OA, manifested as reduced cartilage injury and increased chondrocytes. Mechanically, NFATC2 bound to the RNF125 promoter and directly regulated RNF125 transcription, as illustrated by luciferase reporter, Ch-IP and DNA pull-down assays. Furthermore, RNF125 overexpression inhibited the nuclear translocation of β-catenin, thus suppressing activation of the Wnt/β-catenin signaling pathway. Also, RNF125 as E3 ubiquitin ligase led to the ubiquitination and degradation of TRIM14 protein, and TRIM14 overexpression efficiently reversed the effects of RNF125 overexpression on OA progression. Totally, this study provides new insights into OA pathogenesis regulated by RNF125. RNF125 may be a novel biomarker for OA therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2020
·
IF 3.263
Fei-fei Pan,Yan-Biao Zheng,Chuan-Jian Shi,Feng-wei Zhang,Jin-fang Zhang,Wei-ming Fu
Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. However, the effective pharmacological approaches remain scanty in clinical practice. As a bioactive flavonoid , apigenin (API) is enriched in common fruits and vegetables. Although pharmacological activities of API have been widely investigated, its biological function in HCC remains obscure. In the present study, we found that API strongly suppressed cell growth and induced apoptosis in HCC cells. Using a xenograft mice model, API was demonstrated to inhibit the in vivo tumor growth. It is known that the long non-coding RNA H19, which is frequently elevated in HCC, plays a vital role in mediating tumorigenesis and cancer progression. Our results demonstrated that H19 was down-regulated by API, and thereby induced the inactivation of the canonical Wnt/β-catenin signaling. In conclusion, our results demonstrated that API was able to suppress tumor growth of HCC through H19-mediated Wnt/β-catenin signaling regulatory axis, suggesting that API may be a promising candidate for developing novel therapeutic approaches against liver cancer.
✓ 已验证
DOI
PubMed
高影响因子
ARCHIVES OF ORAL BIOLOGY
·
2020
·
IF 1.931
Ying Bian,Juan Xiang
Background Osteogenic differentiation of human periodontal ligament cells (hPDLCs) is crucial for regenerate periodontal tissues. In this study, we investigated the function of salvianolic acid B (Sal B) in osteogenesis of hPDLCs. Methods HPDLCs were isolated from healthy third molar roots. HPDLCs at passage 3 were identified by morphological observation and immunohistochemistry of vimentin . The viability of hPDLCs incubated with Sal B at concentrations of 0μM, 0.1μM, 0.5μM, 1μM and 5μM were measured by CCK-8 assay. To evaluate the effect of Sal B on osteogenic differentiation of hPDLCs, the alkaline phosphatase (ALP) activity, osteogenic differentiation markers, and mineralized nodules were determined by ALP kit, qRT-PCR and alizarin red S staining, respectively. To confirm the function of Sal B in hPDLCs involved in Wnt/β-catenin signaling pathway , hPDLCs were incubated with Sal B or co-incubated with Sal B and DKK-1 (a inhibitor of Wnt/β-catenin). The levels of Wnt/β-catenin signaling pathway and osteogenic differentiation-associated indicators were then determined. Results HPDLCs showed a typical fibroblast-like and spindle-shaped, with vimentin-positive. The viability of hPDLCs had no obvious change with stimulation of Sal B at various doses. Sal B promoted the increase of ALP activity, osteogenic differentiation markers levels, mineralized nodules and activation of Wnt/β-catenin signaling pathway, and DKK-1 could block those effects of Sal B on hPDLCs. Conclusion Sal B promoted osteogenesis of hPDLCs through Wnt/β-catenin signaling pathway, which providing a potential drug for periodontitis treatment .
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2020
·Vol. 34
·期 3
·3583-3593
·
IF 4.966
Bu Yang,Shangfu Li,Zheng Chen,Feng Feng,Lei He,Bin Liu,Tianwei He,Xuan Wang,Ruiqiang Chen,Zihao Chen,Peigen Xie,Limin Rong
Background Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. Results In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix + (osteoblastic) cells but decreased TRAP + cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β-catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β-catenin inhibitor) treatment. In the co-culture system, Aβ treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP + RAW264.7 cells (pre-osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aβ treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEOPLASIA
·
2021
·
IF 5.715
Yihui Ma,Peiyi Xia,Zhengyang Wang,Jingjing Xu,Lan Zhang,Yanan Jiang
Protein Disulfide Isomerase Family A Member 6 (PDIA6) is an endoplasmic reticulum protein that is capable of catalyzing protein folding and disulfide bond formation. Abnormally elevated expression of PDIA6 has been reported to predict poor outcomes in various cancers. Herein, gain-of- and loss-of-function experiments were performed to investigate how PDIA6 participated in the carcinogenesis of pancreatic cancer (PC). By analyzing the protein expression of PDIA6 in 28 paired PC and para carcinoma specimens, we first found that PDIA6 expression was higher in PC samples. Both the overall survival and disease-free survival rates of PC patients with higher PDIA6 expression were poorer than those with lower PDIA6 ( n = 178). Furthermore, knockdown of PDIA6 impaired the malignancies of PC cells — suppressed cell proliferation, invasion, migration, cisplatin resistance, and xenografted tumor growth. PDIA6-silenced PC cells were more sensitive to cytotoxic natural killer (NK) cells. Overexpression of PDIA6 had opposite effects on PC cells. Interestingly, COP9 signalosome subunit 5 (CSN5), a regulator of E3 ubiquitin ligases known to promote deubiquitination of its downstream targets, was demonstrated to interact with PDIA6, and its expression was increased in PC cells overexpressing PDIA6. Additionally, PDIA6 overexpression promoted deubiquitination of β-catenin and PD-L1 and subsequently upregulated their expression in PC cells. These alterations were partly reversed by CSN5 shRNA. Collectively, the above results demonstrate that PDIA6 contributes to PC progression, which may be associated with CSN5-regulated deubiquitination of β-catenin and PD-L1. Our findings suggest PDIA6 as a potential target for the treatment of PC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Cancer Research
·
2019
·
IF 1.07
Heqi Bu,Dianlei Liu,Junhui Cui,Ke Cai,Feng Shen
Background Oridonin has been demonstrated to have anticancer effect on all kinds of cancer cells and it has shown anti-tumor activity in some tumors partially via the inactivation of Wnt/β-catenin signaling pathway. The study investigated the anticancer effect of oridonin on colon carcinoma cell line COLO205 and explored underlying mechanism. Methods Cell Counting Kit-8 (CCK-8) assay was performed to assess cell viability. Flow cytometry was performed to analyze the apoptosis. The key target genes and proteins involved in Wnt/β-catenin pathway were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The xenograft tumor model of colon cancer COLO205 cell was introduced to detect anti-tumor effects in vivo . Transferase-mediated dUTP nick end labeling (TUNEL) assay was adopted to test the apoptotic cells in the tumor tissues. Results Oridonin inhibited the proliferation of colon cancer COLO205 cells in a dose-dependent and time-dependent manner. Oridonin induced apoptosis by increasing the cleavage of caspases in vitro . Furthermore, the expression levels of β-catenin and its downstream targets, including c-myc, cyclinD1 and survivin were significantly reduced. Nevertheless the knockdown of β-catenin by specific small interfering RNA (siRNA) could augment the anti-proliferative and pro-apoptotic effects by oridonin in COLO205 cells. Meanwhile, oridonin also increased protein expression level of glycogen synthase kinase 3β (GSK3β) and decreased the phosphorylation level of GSK3β. In vivo , oridonin treatment significantly suppressed tumor growth of COLO205 cell xenografts, and which was accompanied by the restrain of Wnt/β-catenin pathway. Conclusions Our present study demonstrated that the growth inhibition and apoptosis induction in colon cancer COLO205 cells by oridonin could be partially mediated through discontinuing Wnt/β-catenin signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biology Direct
·
2024
·Vol. 19
·期 1
·1-14
·
IF 5.7
Sun Tong,Yang Zhiguang
Six-transmembrane epithelial antigen of prostate 3 (STEAP3) is associated with the progression of several human malignancies. However, its role in lung squamous cell carcinoma (LUSC) remains unclear. We measured STEAP3 expression in LUSC cell lines and tissues. LUSC cells with stable STEAP3 overexpression and knockdown were obtained through G418 selection. Multiple assays were used to evaluate the malignant phenotypes of LUSC cells and the activation of the β-catenin signaling. The potential transcriptional regulatory factors of STEAP3 were predicted using the JASPAR database, and the correlation between transcription factor AP-2 gamma (TFAP2C) and STEAP3 was analyzed through the GEPIA database. The study evaluated the regulatory relationship between a potential transcription factor and STEAP3 through ChIP and luciferase reporter assays. Additionally, rescue assays were utilized to ascertain whether TFAP2C serves as the upstream regulatory factor of STEAP3, contributing to LUSC progression. Finally, tumor growth and metastasis were evaluated in vivo. STEAP3 expression was notably higher in LUSC, and its overexpression was linked to a poor prognosis. Moreover, STEAP3 overexpression activated the β-catenin pathway, thereby accelerating cell proliferation and metastasis. Conversely, STEAP3 knockdown had an anti-tumor effect in LUSC. Additionally, TFAP2C bound directly to the STEAP3 promoter and positively regulate its expression in LUSC. The anti-tumor effects of TFAP2C knockdown were partially reversed by STEAP3 overexpression. The study indicates that the TFAP2C/STEAP3 axis may be a therapeutic target for LUSC treatment. This enhances our understanding of lung carcinogenesis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
·
2024
·
IF 3
Junyi Jin,Yihui Wang,Yaoyuan Hu
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. STAM binding protein-like 1 (STAMBPL1), a key member of the COP9 signalosome subunit 5/serine protease 27/proteasome 26S subunit non-ATPase 7 (JAMM) family, is closely associated with tumor development. In this work, data from GSE101728 and GSE84402 chips were analyzed, and STAMBPL1 was selected as the target factor. This study aimed to reveal the potential function of STAMBPL1 in HCC. Clinical results showed that STAMBPL1 was significantly increased in tumor tissues of HCC patients, and its expression was strongly associated with tumor size and TNM stage. Furthermore, STAMBPL1-overexpressed Hep3B2.1-7 cell line or STAMBPL1-silenced SNU-182 cell line were established using lentivirus carrying cDNA encoding STAMBPL1 mRNA or shRNA targeting STAMBPL1, respectively. STAMBPL1-overexpressed cells exhibited a pronounced enhancement of proliferation in vitro and in vivo. Exogenous expression of STAMBPL1 increased the percentage of cells in the S phase and upregulated the expressions of CyclinD1 and Survivin. As expected, STAMBPL1 knockdown exhibited completely opposite effects, resulting in impaired tumorigenicity in vitro and in vivo. Mechanistically, STAMBPL1 activated Wnt/β-catenin pathway and increased the expression of downstream cancer-promoting genes. Interestingly, we found that STAMBPL1 was transcriptionally regulated by sterol regulatory element-binding protein 1 (SREBP1), a modulator of lipid metabolism, as evidenced by luciferase reporter and chromatin-immunoprecipitation (Ch-IP) assays. Notably, STAMBPL1 overexpression increased lipid accumulation in HCC cells and xenograft tumors. Totally our findings suggest that STAMBPL1 plays a vital role in the tumorigenicity of HCC cells. Modulation of Wnt/β-catenin and lipid metabolism may contribute to its pro-cancer effects. STAMBPL1 may serve as a therapeutic target of HCC.
✓ 已验证
DOI
PubMed
高影响因子
APOPTOSIS
·
2023
·
IF 7.2
Pei Lipeng,Zhao Feng,Zhang Yi
Epithelial ovarian cancer (EOC) is the leading cause of cancer death all over the world. USP43 functions as a tumor promoter in various malignant cancers. Nevertheless, the biological roles and mechanisms of USP43 in EOC remain unknown. In this study, USP43 was highly expressed in EOC tissues and cells, and high expression of USP43 were associated with a poor prognosis of EOC. USP43 overexpression promoted EOC cell proliferation, enhanced the ability of migration and invasion, decreased cisplatin sensitivity and inhibited apoptosis. Knockdown of USP43 in vitro effectively retarded above malignant progression of EOC. In vivo xenograft tumors, silencing USP43 slowed tumor growth and enhanced cisplatin sensitivity. Mechanistically, USP43 inhibited HDAC2 degradation and enhanced HDAC2 protein stability through its deubiquitylation function. USP43 diminished the sensitivity of EOC cells to cisplatin through activation of the Wnt/β-catenin signaling pathway mediated by HDAC2. Taken together, the data in this study revealed the functions of USP43 in proliferation, migration, invasion, chemoresistance of EOC cells, and the mechanism of HDAC2-mediated Wnt/β-catenin signaling pathway. Thus, USP43 might serve as a potential target for the control of ovarian cancer progression.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）