CELL TRANSPLANTATION
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2021
·
IF 4.064
Xiao-Yu Chen,Sheng-Yong Yang,Xiao-Jie Ruan,Hong-Yue Ding,Ning-Xi Wang,Fang Liu,Jia-Chu Li,Yi Li
Methionine sulfoxide reductase B1 (MsrB1) can catalyze both free and protein-bound R-methionine sulfoxides (R-MetO) to methionine (Met). It has been reported that MsrB1 plays an important role in the development of HCC and human bone osteosarcoma. However, little is known about the functions of MsrB1 in human colorectal cancer (CRC). Herein, we detected MsrB1 expression level in CRC tissue and cell lines, and investigated the effect of MsrB1 knockdown on CRC phenotypes and possible mechanisms involved in. The results showed that MsrB1 was highly expressed in both CRC tissues and cell lines, and that cell proliferation, migration and invasion were significantly inhibited, but apoptosis was increased after MsrB1 knockdown in colorectal cancer HCT116 and RKO cell lines, compared to control siRNA group. In addition, E-cadherin protein level was increased, vimentin and Snail protein were greatly decreased after knockdown of MsrB1 in cells. Furthermore, pGSK-3β (Ser9) and β-catenin protein levels were reduced, the promoter activity of TCF/LEF construction was inhibited after MsrB1 knockdown in cells, suggesting that GSK-3β/β-catenin signaling axis was involved in the tumorigenesis of CRC. In conclusion, the oncogenic role and related mechanisms of MsrB1 in CRC discovered in our work determined the potential role of MsrB1 as a biomarker and may provide a new target for clinical therapy of CRC.
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高影响因子
BIOSCIENCE REPORTS
·
2019
·Vol. 39
·期 1
·
IF 2.535
Chen Gang,Chen Weicheng,Ye Ming,Tan Weiqiang,Jia Bing
Neuroblastoma is the most common tumor in children, with a very poor prognosis. It is urgent to identify novel biomarkers to treat neuroblastoma, together with surgery, chemotherapy, and radiation. Human tripartite motif 59 (TRIM59), a member of the TRIM family, has been reported to participate in several human tumors. However, the exact role of TRIM59 in neuroblastoma is unknown. In the present study, real-time PCR and Western blot were used to measure mRNA and protein levels of TRIM59 in four neuroblastoma cell lines and in neuroblastoma tissues. Lentiviruses targeting TRIM59 were used to up/down-regulate TRIM59 expression levels. Cell Counting Kit-8 and Annexin-V/PI were used to analyze cell proliferation and apoptosis in neuroblastoma cell lines. Our data showed that TRIM59 knockdown inhibits cell proliferation while inducing apoptosis in SH-SY5Y and SK-N-SH neuroblastoma cell lines. TRIM59 knockdown up-regulated expression of Bax and Bim and down-regulated levels of Survivin, β-catenin, and c-myc. Interestingly, the inhibition of cell proliferation caused by TRIM59 knockdown could be blocked by LiCl, which is an agonist of Wnt/β-catenin signaling pathway. In contrast, TRIM59 overexpression could increase cell proliferation, up-regulate Survivin, β-catenin and c-myc, down-regulate Bax and Bim, and these effects could be blocked by XAV939, which is an inhibitor of Wnt/β-catenin signaling pathway. In addition, TRIM59 was up-regulated and positively related with β-catenin in neuroblastoma tissues. In conclusion, TRIM59 was up-regulated in neuroblastoma, and TRIM59 knockdown inhibited cell proliferation by down-regulating the Wnt/β-catenin signaling pathway in neuroblastoma.
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MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
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2024
·
IF 2.3
Zhihao Zhang,Dongliang Zhang,Kai Su,Dongqiang Wu,Qiqi Hu,Tianying Jin,Tingting Ye,Rongrong Zhang
Background Lung adenocarcinoma (LUAD) patients are implicated in poor prognoses and increased mortality rates. Metastasis, as a leading cause of LUAD-related deaths, requires further investigation. Highly metastatic cancer cells often exhibit extensive characteristics of epithelial-mesenchymal transition (EMT). This study attempted to identify novel targets associated with LUAD metastasis and validate their specific molecular mechanisms. Methods Bioinformatics was conducted to determine NTSR1 expression in LUAD and the enriched pathways. Immunohistochemical analysis was used to assess NTSR1 expression in LUAD tissue. qRT-PCR examined expressions of NTSR1 and Wnt/β-Catenin pathway-related genes in LUAD cells. Transwell assayed cell migration and invasion. Cell adhesion experiments were conducted to evaluate cell adhesion capacity. Western blot analysis was employed to examine expression of EMT, Wnt/β-Catenin pathway, and cell adhesion markers. Results NTSR1 was upregulated in LUAD tissues and cells, and enriched in EMT pathway. Knockdown of NTSR1 reduced migration, invasion, and adhesion abilities in LUAD cells, and inhibited EMT progression and Wnt/β-Catenin pathway. Rescue experiments demonstrated that β-Catenin activator SKL2001 reversed repressive influence of NTSR1 knockdown on LUAD cell malignant phenotypes and EMT progression. Conclusion The data obtained in this study suggested that NTSR1 stimulated EMT and metastasis in LUAD via Wnt/β-Catenin pathway. This finding may provide options for overcoming LUAD metastasis.
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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.
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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.
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2015
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IF 2.084
Zheng Cao,Yang Fu,Xudong Sun,Qiuyue Zhang,Feibo Xu,Yanfei Li
Exposure to aluminum (Al) suppresses bone formation. Osteoblastic differentiation plays a key role in the process of bone formation. However, the effect of Al on osteoblastic differentiation is still controversial, and the mechanism remains unclear. To investigate the effect of Al on osteoblastic differentiation and whether Wnt signaling pathway was involved in it, the primary rat osteoblasts were exposed to 1/40 IC50, 1/20 IC50 and 1/10 IC50 of aluminum trichloride (AlCl 3 ) for 24 h, respectively. The activity analysis of alkaline phosphate, qRT-PCR analysis of type I collagen, alkaline phosphate, Wnt3a and Dkk-1, Western blot analysis of p-GSK3β, GSK3β and β-catenin protein and Immunofluorescence staining for β-catenin suggested that AlCl 3 inhibited osteoblastic differentiation and Wnt/β-catenin pathway. Moreover, we found exogenous Wnt3a application reversed the inhibitory effect of AlCl 3 on osteoblastic differentiation, accompanied by activating the Wnt/β-catenin pathway. Taken together, these findings suggest that AlCl 3 inhibites osteoblastic differentiation through inactivation of Wnt/β-catenin pathway in osteoblasts.
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MOLECULAR THERAPY
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2020
·
IF 8.986
Qiong Wu,Jiali Ma,Jue Wei,Wenying Meng,Yugang Wang,Min Shi
Long non-coding RNAs (lncRNAs) are under active investigation in the development of cancers, including gastric cancer (GC). Oncogenic autophagy is required for cancer cell survival. The present study aimed to investigate the regulatory role of lncRNA small nucleolar host gene 11 (SNHG11) in GC. We show that SNHG11 is upregulated in GC, and that its upregulation correlated with dismal patient outcomes. Functionally, SNHG11 aggravated oncogenic autophagy to facilitate cell proliferation, stemness, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in GC. Mechanistically, SNHG11 post-transcriptionally upregulated catenin beta 1 (CTNNB1) and autophagy related 12 (ATG12) through miR-483-3p/miR-1276, while the processing of precursor (pre-)miR-483/pre-miR-1276 was hindered by SNHG11. SNHG11 induced GSK-3β ubiquitination through interacting with Cullin 4A (CUL4A) to further activate the Wnt/β-catenin pathway. Intriguingly, SNHG11 regulated autophagy in a manner dependent on ATG12 rather than the Wnt/β-catenin pathway, whereas SNHG11 contributed to the malignant behaviors of GC cells via both pathways. Finally, SNHG11 upregulation in GC cells was shown to be transcriptionally induced by TCF7L2. In conclusion, we reveal that SNHG11 is an onco-lncRNA in GC and might be a promising prognostic and therapeutic target for GC.
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MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 4.7
Zhang Qi,Ren Xinxiang,Cao Wanshuang,Shi Hongfei,Zhu Mingming
Prostate cancer is one of the most common malignant tumors in men, with prostate cancer stem cells (PCSCs) playing an important role in its initiation and progression. Accumulating evidence has demonstrated that lactate and lactate-mediated histone lactylation are crucial regulators of proliferation, metastasis, immune escape and drug resistance in various cancer. However, their functional roles and underlying mechanisms in PCSCs remain largely elusive. In the present study, we found that lactate levels were significantly elevated in PCSC microenvironment, which effectively induced H3K18 lactylation (H3K18la). The increased-lactate enhanced the stemness of PCSCs. ChIP analysis revealed that H3K18la positively regulated the transcription of the β-catenin gene. Furthermore, β-catenin transcriptionally activated lactate dehydrogenase A (LDHA) to promote lactate production, thereby forming a lactate/H3K18la/β-catenin/LDHA positive feedback loop. Notably, luteolin, a natural flavone, disrupted this feedback loop and exerted potent inhibitory effects on PCSCs. Collectively, our findings uncover a novel lactate-driven regulatory axis in PCSCs and provide new insights into the development of intervention strategies in prostate cancer. Graphical abstract
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Frontiers in Bioscience-Landmark
·
2026
·Vol. 31
·期 8
·
IF 4.1
Yulian Shi,Tingyu Fan,Rongmei Qu,Guosheng Wu,Xiangtian Li,Jiaxuan Liu,Ziyi Feng,Haopeng Wu,Jun Ouyang,Jingxing Dai
Background:
Bone tissue possesses strong regenerative potential, but large segmental bone defects often exceed its intrinsic capacity for self-healing. Human adipose-derived stem cells (hASCs) offer a promising cellular basis for bone regeneration owing to their robust osteogenic differentiation potential. However, the role of PDZ and LIM domain 2 (PDLIM2) play in hASC osteogenesis and its relationship with the Wnt/β-catenin signaling pathway remain poorly understood.
Methods:
Western blotting, immunofluorescence staining, Alizarin Red S staining, alkaline phosphatase activity assays, wound healing assays, and Transwell assays were employed to assess osteogenic differentiation, osteogenic capacity, and cellular migration. Lentivirus-mediated PDLIM2 knockdown, cytochalasin D (CytoD) intervention, microfilament stabilizer treatment, and β-catenin activator treatment were used as a means of validating the regulatory mechanism.
Results:
hASCs exhibited the ability to undergo osteogenic differentiation. During this osteogenic process, significant increases in PDLIM2, β-actin, and β-catenin expression were observed, with PDLIM2 expression reaching 2–3 times that of the control group on day 14, whereas β-actin and β-catenin levels peaked on day 7 (1.5–2 times those in the control group). Lentivirus-mediated PDLIM2 knockdown reduced β-actin expression by approximately 5-fold and β-catenin expression by approximately 1.7-fold, accompanied by cytoskeletal disorganization and impaired osteogenic differentiation. Actin microfilament integrity was found to regulate osteogenic marker expression and alkaline phosphatase activity, while CytoD treatment suppressed β-actin and β-catenin expression to approximately 50% of control levels and inhibited osteogenic differentiation. Knocking down PDLIM2 attenuated the responsiveness of hASCs to microfilament stabilizers and β-catenin activators.
Conclusions:
This study demonstrates that PDLIM2 may be functionally associated with β-catenin nuclear translocation, potentially through the remodeling of the actin cytoskeleton. These findings provide preliminary mechanistic insight and warrant further validation.
Keywords
PDLIM2human adipose-derived stem cells (hASCs)osteogenesiscytoskeletonβ-catenin
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Oncogenesis
·
2026
·
IF 6
Shen Tao,Ma Yuejiang,Wu Tingting,Cao Zhu,Yi Peng,Huang Xiufeng,Yang Shizhou
High-risk human papillomavirus (HPV) is a causal factor in cervical cancer, driving the cancer’s initiation and progression. Although cancer stem cells (CSCs) have been implicated in maintaining the stemness and malignancy of cervical cancer cells, the underlying mechanisms are not yet fully understood. In this study, we modulated gene expression in Caski and SiHa cervical cancer cells using siRNA and overexpression approaches. Functional assays, including MTT, transwell, RT-qPCR, western blotting, immunohistochemistry, luciferase reporter, immunofluorescence, and sphere formation, were performed to evaluate target gene expression. Additionally, transcriptome sequencing was used to analyze the impact of silencing HPV16 E7 on SiHa cells, and a xenograft model was assessed for in vivo effects. Our transcriptome sequencing reveals substantial changes in gene expression profiles upon HPV16 E7 silencing in cervical cancer. Notably, we identified APC2 as a key downstream target transcriptionally activated by HPV16 E7 through the transcription factor E2F1, and its elevated expression is associated with poor prognosis in cervical cancer. Surprisingly, APC2 exhibits oncogeneic properties in cervical cancer by activating the Wnt/β-catenin pathway, and its overexpression reverses the inhibitory effects of HPV16 E7 silencing on malignancy and CSC properties. Additionally, SPIN4 is identified as a pivotal downstream target of the HPV16 E7/APC2 axis, positively modulating cervical cancer progression. Our study reveals a novel HPV16 E7-APC2-SPIN4 axis as a key driver of cervical cancer. In this pathway, APC2 unexpectedly functions as an oncogene by activating the Wnt/β-catenin signaling to promote tumorigenesis and CSC properties.
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Cell Reports Medicine
·
2026
·
IF 14
Qiang Zhang,Yue Kong,Yinglin Long,Xue Li,Liang Wang,Zhanhao Luo,Xiaoya Yang,Yanchun Xie,Quanwei Yu,Jing Yu,Dayi Liang,Wenhao Yuan,Xiaomin Cheng,Yaqi Su,Kaisa Cui,Guobao Tian,Zhen He,Ping Lan
Immune evasion remains a major challenge in colorectal cancer (CRC) treatment. Here, we identify that druggable β-catenin palmitoylation at cysteine 466 (C466) by ZDHHC5 acts as a competitive switch, displacing S-nitrosylation and coordinating an immunosuppressive program. The palmitoylated state stabilizes the β-catenin/TCF4 complex, which simultaneously upregulates SLC7A11 to suppress immunogenic ferroptosis, critical for CD8 + T cell priming, and PD-L1 to inhibit cytotoxic CD8 + T cells, thereby impairing both the initiation and effector phases of anti-tumor immunity. Clinically, ZDHHC5 expression predicts poor survival and resistance to anti-PD-L1 therapy. Silencing ZDHHC5 reduced tumor growth in patient-derived organoids and xenografts, while Zdhhc5 ablation in mice inhibited CRC progression by reversing immunogenic ferroptosis suppression and alleviating PD-L1-mediated T cell inhibition. Importantly, β-cat-oxazole, a first-in-class inhibitor, disrupts ZDHHC5-β-catenin binding, thereby restoring immunogenic ferroptosis and blocking PD-L1-mediated immunosuppression, ultimately suppressing tumor growth. Our findings establish targeting of this palmitoyl-switch as a precision strategy to overcome therapeutic resistance.
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BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2023
·Vol. 46
·期 1
·74-85
·
IF 2
Jianchao He,Yuhui Bu,Xiaolong Li,Xiaojun Zhang,Li Ma
Breast cancer (BC) is the most generally diagnosed cancer and the driving cause of cancer-related death. Transmembrane (TMEM) proteins have been reported to serve as prognostic indicators in a variety of cancers, and it can offer therapeutic targets for carcinoma. However, the function of TMEM in BC remains unclear. In this study, TMEM9A, a member of TMEM family, was screened as the candidate gene after analyzing the profiles of GSE42568 and GEPIA-BRCA database via bioinformatic method. The upregulated expression of TMEM9A was confirmed in BC samples compared with the paired normal tissues. Hence, we speculated that TMEM9A might promote BC progression. To test the hypothesis, we performed a series of loss/gain-of-function experiments and found that BC cells with TMEM9A deletion inhibited cell proliferation, migration, and invasion along with induced apoptosis. Conversely, TMEM9A overexpression reversed the trend. Mechanically, TMEM9A knockdown blocked the Wnt/β-catenin signaling pathway as evidenced by the increased adenomatous polyposis coli (APC) expression and decreased β-catenin, cyclin D1, and axis inhibition protein 2 (AXIN2) expression. Furthermore, over-activation of the Wnt/β-catenin pathway by transfecting BC cells with β-Catenin-S33Y (β-Catenin tyrosine for serine at codon 33) plasmids reversed the effects caused by TMEM9A knockdown. In conclusion, TMEM9A may play a tumor-promoting role in BC progression via activating the Wnt/β-catenin signaling pathway. Therefore, TMEM9A may be an effective therapeutic option for BC.
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