Experimental and Therapeutic Medicine
·
2023
·Vol. 27
·期 1
·1-13
·
IF 2.7
Qiankun Quan,Xinxin Ma,Ming Li,Xi Li,Haifeng Yuan
β‑Amyloid peptide (Aβ) deposition in the brain is an important pathological change in Alzheimer's disease (AD). Insulin‑degrading enzyme (IDE), which is regulated transcriptionally by peroxisome proliferator‑activated receptor γ (PPARγ), is able to proteolyze Aβ. One of the members of the MAPK family, ERK, is able to mediate the phosphorylation of PPARγ at Ser112, thereby inhibiting its transcriptional activity. Ginsenoside Rg1 is one of the active ingredients in the natural medicine ginseng and has inhibitory effects on Aβ production. The present study was designed to investigate whether ginsenoside Rg1 is able to affect the regulation of PPARγ based on the expression of its target gene, IDE, and whether it is able to promote Aβ degradation via inhibition of the ERK/PPARγ phosphorylation pathway. In the present study, primary cultured rat hippocampal neurons were treated with Aβ1‑42, ginsenoside Rg1 and the ERK inhibitor PD98059, and subsequently TUNEL staining was used to detect the level of neuronal apoptosis. ELISA was subsequently employed to detect the intra‑ and extracellular Aβ1‑42 levels, immunofluorescence staining and western blotting were used to detect the translocation of ERK from the cytoplasm to the nucleus, immunofluorescence double staining was used to detect the co‑expression of ERK and PPARγ, and finally, western blotting was used to detect the phosphorylation of PPARγ at Ser112 and IDE expression. The results demonstrated that ginsenoside Rg1 or PD98059 were able to inhibit primary cultured hippocampal neuron apoptosis induced by Aβ1‑42 treatment, reduce the levels of intra‑ and extraneuronal Aβ1‑42 and inhibit the translocation of ERK from the cytoplasm to the nucleus. Furthermore, administration of ginsenoside Rg1 or PD98059 resulted in attenuated co‑expression of ERK and PPARγ, inhibition of phosphorylation of PPARγ at Ser112 mediated by ERK and an increase in IDE expression. In addition, the effects when PD98059 to inhibit ERK followed by treatment with ginsenoside Rg1 were found to be more pronounced than those when using PD98059 alone. In conclusion, ginsenoside Rg1 was demonstrated to exert neuroprotective effects on AD via inhibition of the ERK/PPARγ phosphorylation pathway, which led to an increase in IDE expression, the promotion of Aβ degradation and the decrease of neuronal apoptosis. These results could provide a theoretical basis for the clinical application of ginsenoside Rg1 in AD.
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Frontiers in Pharmacology
·
2023
·
IF 5.6
Sisi Ruan,Jiqing Xie,Linhai Wang,Lulu Guo,Yan Li,Wu Fan,Rongzhan Ji,Zhenlin Gong,Yan Xu,Jian Mao,Jianping Xie
Introduction: Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson’s disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo . Methods: We established a PD model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL6 mice (25 mg/kg/d, 5 d, i.p.) to investigate the neuropharmacological modulation of Nic pretreatment (2.5 mg/kg/d, 5 d, i.p., 30 min before MPTP injection) from the perspectives of neurobehavioral assessment, the pathological alterations, microglial cell inflammation and MAPK signaling pathways in specific brain regions. Results: The open field test, elevated plus maze, rotarod and traction test suggested that Nic pretreatment could significantly improve MPTP-induced motor impairment and had an anxiolytic effect. Nic was found to improve neuroapoptosis, enhance tyrosine hydroxylase activity, and reduce the accumulation of the phosphorylated α-synuclein in the substantia nigra and striatal regions of PD mice by TUNEL and immunohistochemical assays. Immuno-fluorescent method for labeling Iba1 and CD68 indicated that Nic remarkably alleviates the activation of microglia which represents the M1 polarization state in the mice brain under MPTP stimulation. No significant difference in the expression of p38/MAPK pathway was found in the nigrostriatal regions, while Nic could significantly inhibit the elevated p-JNK/JNK ratio and increase the declined p-ERK/ERK ratio in the substantia nigra of MPTP-exposed brains, which was further confirmed by the pretreatment of CYP2A5 inhibitor to decline the metabolic activity of Nic. Discussion: The molecular signaling mechanism by which Nic exerts its neuroprotective effects against PD may be achieved by regulating the JNK and ERK signaling pathways in the nigra-striatum related brain regions.
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JOURNAL OF MEDICAL VIROLOGY
·
2025
·Vol. 97
·期 3
·e70267
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IF 4.6
Wenting Mao,Yi Wan,Yang Liu,Minmin Zhou,Xiaoying Jia,Yuxia Hou,Wei Wang
The lymphocytic choriomeningitis virus (LCMV) is a widespread pathogen that causes mild-to-severe infections to severe outcomes. In this study, we explored the potential of trametinib, a mitogen-activated protein kinase (MAPK) inhibitor, as an antiviral agent against LCMV. Trametinib demonstrated significant antiviral activity against two distinct LCMV strains, Armstrong and Cl13, with promising half-maximal inhibitory concentrations (IC 50 ) and selectivity indices (SI) indicating its potency and safety profile. Mechanistic investigations revealed that trametinib interfered with multiple stages of the LCMV life cycle, including membrane fusion and genomic replication, leading to the robust inhibition of viral proliferation. Furthermore, trametinib disrupted the MEK/ERK signaling pathway, which is crucial for LCMV infection. In both in vitro and in vivo experiments, trametinib effectively reduced viral loads and mitigated pathological damage to the spleen and liver tissues. Overall, our findings suggest that trametinib is a promising novel therapeutic option for combating LCMV infection by targeting key stages of the viral life cycle and disrupting host cellular signaling pathways. Further exploration of the antiviral properties of trametinib is likely to pave the way for its clinical development as a treatment for LCMV infections.
研究领域:
病毒学
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药物研发
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医学
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Yi-Min Ren,Yu Chen,Chang-Mao Jiang,Xiong Chen,Hong-Jin Qin,Zhu Wei,Xue Rao,Yu-Chen Wang,Ning-Ze Jiang,Jin-Yuan Luo-Qian,Ying-Nan Song,Xiao-Hua Zou,Jiang Zheng,Hong-Jin Chen
Chronic inflammatory pain (CIP) poses a significant medical challenge, with current pharmacological treatments often associated with considerable side effects. The identification of effective therapeutic targets and the development of novel agents remain major hurdles. Exploring neuroimmune interactions and utilizing network pharmacology to uncover compounds capable of simultaneously modulating pain and inflammation presents a promising strategy. In this study, the therapeutic efficacy, potential targets, and underlying mechanisms of isoliquiritigenin (ISL) were investigated in a mouse model of CIP induced by complete Freund's adjuvant (CFA) paw pad injection. Single-dose ISL (20 or 60 mg/kg) attenuated CFA-induced hypersensitivity in an acute screening experiment, after which we investigated sustained efficacy using ISL (10 mg/kg) once daily for 7 days. ISL treatment significantly reduced paw swelling, mechanical allodynia, and thermal hyperalgesia. Additionally, ISL lowered the levels of IL-6, TNF-α, and VCAM-1 in both dorsal root ganglia (DRG) and skin tissues, along with a significant reduction in ERK phosphorylation. Network pharmacology analysis and molecular docking suggested CCR2 as a potential target of ISL. Further investigation revealed that ISL attenuated CCL7-induced CCR2 signaling activation. To validate the involvement of CCR2, siRNA-mediated knockdown of CCR2 was performed via DRG injection. This intervention suppressed ISL's analgesic and anti-inflammatory effects in CIP mice and CCL7 paw pad injection-induced pain and inflammation. Moreover, activation of ERK using tert-butylhydroquinone in CCR2 knockdown mice exacerbated CFA-induced inflammatory responses. These findings suggest that ISL alleviates CIP by targeting the CCL7/CCR2 axis and suppressing ERK-mediated inflammation.
研究领域:
药理学
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神经科学
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免疫学
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疼痛研究
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分子生物学
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2016
·Vol. 408
·期 26
·7491-7503
·
IF 3.125
Yang Ting,Xu Feifei,Sheng Yuan,Zhang Wen,Chen Yun
Apoptosis suppression caused by overexpression of anti-apoptotic proteins is a central factor to the acquisition of multi-drug resistance (MDR) in breast cancer. As a highly conserved anti-apoptotic protein, Bcl-2 can initiate an anti-apoptosis response via an ERK1/2-mediated pathway. However, the details therein are still far from completely understood and a quantitative description of the associated proteins in the biological context may provide more insights into this process. Following our previous attempts in the quantitative analysis of MDR mechanisms, liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics was continually employed here to describe ERK/Bcl-2-mediated anti-apoptosis. A targeted proteomics assay was developed and validated first for the simultaneous quantification of ERK1/2 and Bcl-2. In particular, ERK isoforms (i.e., ERK1 and ERK2) and their differential phosphorylated forms including isobaric ones were distinguished. Using this assay, differential protein levels and site-specific phosphorylation stoichiometry were observed in parental drug-sensitive MCF-7/WT cancer cells and drug-resistant MCF-7/ADR cancer cells and breast tissue samples from two groups of patients who were either suspected or diagnosed to have drug resistance. In addition, quantitative analysis of the time course of both ERK1/2 and Bcl-2 in doxorubicin (DOX)-treated MCF-7/WT cells confirmed these findings. Overall, we propose that targeted proteomics can be used generally to resolve more complex cellular events.
研究领域:
癌症生物学
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药理学
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蛋白质组学
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分子生物学
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Evidence-based Complementary and Alternative Medicine
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2021
·
IF 2.63
Huanhuan Zhang,Wenying Yu,Liting Ji,Yusen Zhong,Yiyou Lin,Huazhong Ying,Chenhuan Yu,Changyu Li
Mucus hypersecretion is a hallmark of chronic obstructive pulmonary disease (COPD) and is associated with increasing sputum production and declining pulmonary function. Therefore, reducing mucus secretion can be a new therapeutic opportunity for preventing COPD. The Guifu Dihuang pill (GFDHP) is a classical Chinese medicine and has been used as an immunoregulator for treatment of kidney yang deficiency syndrome, including hypothyroidism, adrenocortical hypofunction, chronic bronchitis, and COPD, for more than 2000 years. However, the protective effects and mechanisms of GFDHP against mucus hypersecretion in COPD remain obscure. The aim of the present study was to explore the inhibitory effects of GFDHP on lipopolysaccharide/cigarette smoke- (LPS/CS-) induced Mucin5ac (Muc5ac) overproduction and airway goblet cell hyperplasia in mice. The mice were randomly assigned into 6 groups: control, model, GFDHP-L, GFDHP-M, GFDHP-H, and dexamethasone. The mice were given LPS twice through intranasal inhalation and then exposed to CS daily for 6 weeks. Three doses of GFDHP were orally administered daily during the last 3 weeks of the experiment. Pulmonary function was examined with an EMKA pulmonary system, and pulmonary hyperpermeability and lung damage were evaluated with an in vivo imaging system. Inflammatory cells and cytokines in bronchoalveolar lavage fluid (BALF) were detected with a cell count analyzer and though ELISA analysis, respectively. Lung pathological changes and airway goblet cell hyperplasia were analyzed with hematoxylin and eosin and Alcian blue periodic acid Schiff staining. The protein expression levels of Muc5ac and extracellular signal-regulated kinase (ERK)-specificity protein1 (SP1) signaling pathway were measured with Western blot and immunohistochemistry. The results demonstrated that GFDHP improved pulmonary function and suppressed mouse pulmonary hyperpermeability and edema. GFDHP suppressed inflammatory cell infiltration and cytokine release in BALF, thereby elevating pulmonary function. It ameliorated lung pathological changes and airway goblet cell hyperplasia, and suppressed expression levels of Muc5ac mRNA and protein and phospho-ERK and SP1 levels in the lung tissues of the COPD mice. In conclusion, GFDHP inhibited mucus hypersecretion induced by LPS/CS by suppressing the activation of the ERK-SP1 pathway.
研究领域:
药理学
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呼吸医学
·
中医
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JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 234
·期 10
·18480-18491
·
IF 4.522
Shi Xu,Beibei Yang,Tingting Tao,Ji Zhang,Yun Liu,Jun Hu,Yi Fan,Guangdong Zhang
Epidemiologic studies have shown a reduced risk of developing Parkinson's disease (PD) among cigarette smokers. Nicotine, as a key component in tobacco products, is thought as a possible candidate for action of smoking in neuroprotection. α7 nicotinic acetylcholine receptors (α7-nAChRs) is one of the most abundant nAChRs in the mammalian brain. Although nicotine is thought to exert this protective action by acting on nicotinic receptors, including the α7-nAChRs; the mechanisms underlying how α7-nAChRs protect against dopaminergic neuron loss are highly complex. Using nicotine and a selective α7-nAChR agonist PNU-282987, we first confirmed that their addition to SH-SY5Y cells challenged with 1-methyl-4-phenylpyridinium (MPP + ) could afford neuroprotection and result in a reduction in apoptotic cell death. Then, we found that the pretreatment with nicotine and PNU-282987 showed the neuroprotective antiapoptotic effects via activating the α7-nAChRs/MAPK/p53 axis. Furthermore, we used RNA interference to silence the expression of α7-nAChRs in SH-SY5Y cells and found that suppressing α7-nAChR expression diminished the antiapoptotic effects of nicotine and PNU-282987, not the toxic effects of MPP + . Moreover, α7-nAChR knockdown could only decrease the inhibitory effects of nicotine and PNU-282987 on the phosphorylated extracellular signal-regulated kinase (ERK), not c-Jun amino-terminal kinase and p38. Therefore, our findings indicate the important roles of ERK/MAPK signaling in the neuroprotective effects of α7-nAChRs and suggest that α7-nAChR agonists may be validated as novel treatments for PD.
研究领域:
神经科学
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药理学
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细胞生物学
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神经退行性疾病
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Clinics and Research in Hepatology and Gastroenterology
·
2021
·
IF 2.947
Huanqiu Liu,Ji Li,Chengwei Jiang,Tong Yuan,Haichun Ma
Objective Hepatic ischemia/reperfusion injury (IRI) is an unsettled and intractable conundrum in clinical treatment after liver transplantation and resection. Cellular communication network factor 1 (CCN1) is upregulated in liver IRI and may play a key role in this process. The objective of this study is to investigate the regulatory mechanism of CCN1 in liver IRI, which may provide new insight into liver IRI clinical treatment. Methods The hepatic ischemia/reperfusion model was established in male C57BL/6 mice by occlusion of vessels in the liver followed by reperfusion. The mice were transfected with two small interfering RNAs (siRNAs) against CCN1 for CCN1 knockdown. The hypoxia/reoxygenation (HR) model was established in vitro using mouse hepatic cells followed by transfection with a siRNA and treatment with an ERK activator TPA to confirm the effects of CCN1 on the MEK/ERK pathway in liver IRI. Results In hepatic IRI, CCN1 was upregulated and its knockdown reduced alanine aminotransferase and aspartate transaminase levels, myeloperoxidase activity, and the levels of IL-6 and TNF-α. CCN1 downregulation alleviated inflammatory cell infiltration and apoptosis in the liver. The expressions of cleaved caspase-9, cleaved caspase-3, Bax, and CHOP were decreased with an increased Bcl-2 level after CCN1 knockdown. The phosphorylation and activation of proteins in ER stress and MEK/ERK pathway were inhibited by CCN1 knockdown. In vitro , the levels of proinflammatory cytokines, apoptosis-inducing proteins, and proteins in ER stress and MEK/ERK pathway, which were decreased by CCN1 knockdown in HR, were restored by TPA, confirming that the activation of ERK aggravated cell apoptosis after reoxygenation. Conclusion Overall, CCN1 knockdown may suppress the inflammation, apoptosis during hepatic IRI by reducing the MEK/ERK pathway activation, which may be a breakthrough point in clinical alleviation of hepatic IRI caused by liver transplantation and resection.
研究领域:
肝病学
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分子生物学
·
细胞生物学
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JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Jiangyan Rao,Hongpu Li,Haonan Zhang,Xiaoxia Xiang,Xinyu Ding,Li Li,Funeng Geng,Hongyi Qi
Ethnopharmacological relevance Periplaneta americana (L.) (PA) has been used in traditional Chinese medicine for thousands of years for the effect of invigorating blood circulation and removing blood stasis . Modern pharmacological research shown that PA extract exhibits promising effects in promoting wound healing and regeneration, as well as in brain diseases such as Parkinson's disease (PD). However, whether it is effective for neuroregeneration and neurological function recovery after stroke still unknown. Aim of the study This study aims to investigate the potential effect of PA extract to promote brain remodeling through the activation of endogenous neurogenesis and angiogenesis, in addition, preliminary exploration of its regulatory mechanism. Methods Firstly, BrdU proliferation assay and immunofluorescence (IF) staining were used to evaluate the effect of PA extract on the neurogenesis and angiogenesis in vitro and in vivo . Subsequently, the effects of PA extract on brain injury in stroke rats were assessed by TTC and HE. While mNSS score, adhesive removal test, rota-rod test, and morris water maze test were used to assess the impact of PA extract on neurological function in post-stroke rats. Finally, the molecular mechanisms of PA extract regulation were explored by RNA-Seq and western blotting . Results The number of BrdU + cells in C17.2 cells, NSCs and BMECs dramatically increased, as well as the expression of astrocyte marker protein GFAP and neuronal marker protein Tuj-1 in C17.2 and NSCs. Moreover, PA extract also increased the number of BrdU + DCX + , BrdU + GFAP + , BrdU + CD31 + cells in the SGZ area of transient middle cerebral artery occlusion model (tMCAO) rats. TTC and HE staining revealed that PA extract significantly reduced the infarction volume and ameliorated the pathological damage. Behavioral tests demonstrated that treatment with PA extract reduced the mNSS score and the time required to remove adhesive tape, while increasing the time spent on the rotarod. Additionally, in the morris water maze test, the frequency of crossing platform and the time spent in the platform quadrant increased. Finally, RNA-Seq and Western blot revealed that PA extract increased the expression of p-ERK, p-CREB and BDNF . Importantly, PA extract mediated proliferation and differentiation of C17.2 and NSCs reversed by the ERK inhibitor SCH772984 and the BDNF inhibitor ANA-12, respectively. Conclusion Our study demonstrated that PA extract promoted neurogenesis and angiogenesis by activating the CREB/ERK signaling pathway and upregulating BDNF expression, thereby recovering neurological dysfunction in post-stroke.
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PHYTOTHERAPY RESEARCH
·
2023
·Vol. 37
·期 4
·1422-1434
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IF 7.2
Yanfei Ban,Yang Wang,Liming Qiao,Chengzhong Zhang,Hongrui Wang,Xuhui He,Dan Jia,Chengjian Zheng
The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1β (IL-1β), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T 1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%–21.89% and 16.29%–22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.
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POULTRY SCIENCE
·
2022
·
IF 4.014
Yusong Miao,Dong Niu,Ze Wang,Jian Wang,Zhiyong Wu,Jiaxin Bao,Xiaodi Jin,Rui Li,Muhammad Ishfaq,Jichang Li
ABSTRACT Mycoplasma gallisepticum ( MG ) is an avian pathogen that commonly causes respiratory diseases in poultry. Methylsulfonylmethane ( MSM ) is a sulfur-containing natural compound that could alleviate inflammatory injury through its excellent anti-inflammatory and antioxidant properties. However, it is still unclear whether MSM prevents MG infection. The purpose of this study is to determine whether MSM has mitigative effects on MG-induced inflammatory injury in chicken and chicken like macrophages ( HD11 cells ). In this research, White Leghorn chickens and HD11 cells were used to build the MG-infection model. Besides, the protective effects of MSM against MG infection were evaluated by detecting MG colonization, histopathological changes, oxidative stress and inflammatory injury of trachea, and HD11 cells. The results revealed that MG infection induced inflammatory injury and oxidative stress in trachea and HD11 cells. However, MSM treatment significantly ameliorated oxidative stress, partially alleviated the abnormal morphological changes and reduced MG colonization under MG infection. Moreover, MSM reduced the mRNA expression of proinflammatory cytokines-related genes and decreased the number of death cells under MG infection. Importantly, the protective effects of MSM were associated with suppression of nuclear factor-kappa B ( NF-κB ) and extracellular signal-related kinases (ERK) /Jun amino terminal kinases (JNK) -mitogen-activated protein kinases ( MAPK ) pathway in trachea and HD11 cells. These results proved that MSM has protective effects on MG-induced inflammation in chicken, and supplied a better strategy for the protective intervention of this disease.
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CELLULAR & MOLECULAR BIOLOGY LETTERS
·
2021
·Vol. 26
·期 1
·1-16
·
IF 5.787
Xing Ying,Liu Yang,Qi Zhong,Liu Zhengrong,Wang Xin,Zhang Hongyi
Background Hepatocellular carcinoma (HCC) is now the second leading cause of cancer death worldwide and lacks effectual therapy due to its high rate of tumor recurrence and metastasis. The aim of this study was to investigate the effects of L antigen family member 3 (LAGE3, a member of the LAGE gene family involved in positive transcription) on the progression of HCC. Methods The expression of LAGE3 was detected by quantitative real-time polymerase chain reaction. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation assay, EdU, and cell cycle analysis assay were employed to evaluate the proliferation of HCC cells. Annexin V-FITC/PI and TUNEL assay were used to assess the apoptosis rate of HCC cells. Wound healing and transwell assay were used to investigate the migration and invasion of HCC cells. A xenograft model of HCC was established with 2 × 10 6 Hep3B or SK-HEP1 cells to investigate the in vivo effects of LAGE3. Then, the protein levels of LAGE3, p-p38, p-38, c-Jun N-terminal kinase (JNK),p-JNK, extracellular signal-regulated kinase (ERK), and p-ERK were detected by western blot. Results We found that LAGE3 was upregulated in HCC tissues compared to adjacent tissues, and its high expression was correlated with poor overall survival by bioinformatics analysis. Next, we manually regulated the expression of LAGE3 in HCC cells. The knockdown of LAGE3 inhibited the proliferation of HCC cells by arresting the cell cycle in G1 phase. Also the downregulation of LAGE3 inhibited cell migration and invasion and induced apoptosis of HCC cells, while overexpression of LAGE3 promoted the malignant phenotypes of HCC. These results were further confirmed by the in vivo growth of HCC xenografts and the inhibition of apoptosis of HCC tumor cells. Furthermore, we found that LAGE3 exerted cancer-promoting effects by potentiating the JNK and ERK signaling pathway. An ERK inhibitor (10 μM SCH772984) or JNK inhibitor (25 μM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells. Conclusions LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway.
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