Gastroenterology Research and Practice
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2022
·
IF 1.919
Sheng Chen,Quan-Jin Dong,Zi-Ang Wan,Shan Gao,Shi-Liang Tu,Rui Chai
Objective. BHLHE41 has been shown to be a marker of tumorigenesis. Colon cancer (CC) is a common malignant tumor of colonic mucosa. This study mainly explored the mechanism of BHLHE41 in alleviating malignant behavior of hypoxia-induced CC cells. Methods. The levels of BHLHE41 in CC and normal cell lines were tested by Western blot and qRT-PCR. After, CC cells were subjected to hypoxia treatment and BHLHE41 overexpression transfection, and the BHLHE41 expression, the effect of BHLHE41 on CC cell viability, apoptosis, migration, and invasion and cell cycle were tested by qRT-PCR and relevant cell functional experiments. HIF-1α and epithelial-mesenchymal transition- (EMT-) related proteins were tested by Western blot. Moreover, CC tumor-bearing model was established in nude mice, and the effect of BHLHE41 on the tumor was evaluated by measuring the tumor volume and weight. Then, the expressions of BHLHE41 and EMT-related proteins were detected by immunohistochemistry and Western blot. Results. Western blot and qRT-PCR showed that BHLHE41 was lowly expressed in CC cells. BHLHE41 overexpression could inhibit the hypoxia-induced CC cell viability, migration, and invasion, induce apoptosis, and alter cell cycle. Besides, BHLHE41 overexpression could enhance the levels of E-cadherin but reduce the levels of HIF-1α, N-cadherin, vimentin, and MMP9 in hypoxia-induced CC cells. Moreover, BHLHE41 overexpression reduced tumor volume, weight, and EMT-related proteins levels in tumor tissues. Conclusions. BHLHE41 overexpression could mitigate the malignant behavior of hypoxia-induced CC via modulating the HIF-1α/EMT pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
Cancers
·
2024
·Vol. 16
·期 19
·3269
·
IF 4.5
Xinyue Zhao,Zhihui Han,Ruiying Liu,Zehao Li,Ling Mei,Yue Jin
Simple SummaryEpithelial-to-mesenchymal transition (EMT) plays a critical role in cancer progression, contributing to the invasive and migratory abilities of tumor cells. In this study, we show that FBXO11 promotes the degradation of ZEB1, a key EMT regulator, via ubiquitination. Loss of FBXO11 increases ZEB1 levels, enhancing the invasiveness of lung cancer cells, while its overexpression reduces ZEB1 and suppresses invasion. Importantly, higher FBXO11 expression is associated with better prognosis in non-small cell lung cancer (NSCLC), highlighting its potential role as a therapeutic target for controlling EMT and cancer metastasis.AbstractEpithelial-to-mesenchymal transition (EMT) affects the invasion and migration of cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung cancer cells.
研究领域:
癌症生物学
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分子生物学
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细胞生物学
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PubMed
高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
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2023
·
IF 2.3
Deng Boya,Zhang Siyang,Zhou Yingying,Zhu Ying,Fei Jing,Li Ailin
Cervical cancer (CC) is the primary cancer-related cause of morbidity and mortality in women. Previous studies have shown that placenta-specific 8 (PLAC8) has different functions in multiple malignancies. This study aimed to explore the function and regulatory mechanism of PLAC8 in CC. Bioinformatics and immunohistochemical analyses demonstrated that PLAC8 was significantly upregulated in CC tissues compared with normal tissues. Gain/loss-of-function experiments showed that siRNA-mediated knockdown of PLAC8 suppressed cell migration and invasion, while PLAC8 overexpression promoted cell motility. Moreover, PLAC8 was revealed to affect the epithelial–mesenchymal transition (EMT) process by upregulating epithelial (E)-cadherin and decreasing the expression of mesenchymal markers of EMT, including vimentin, zinc finger E-box binding homeobox 1 (ZEB1), neural (N)-cadherin, matrix metalloproteinase-9 (MMP-9), and MMP-2 in PLAC8-silenced cells. PLAC8 activated the AKT pathway, as proven by the downregulation of p-AKT Ser473 and p-AKT Thr308 expression after PLAC8 knockdown. Furthermore, PLAC8 overexpression upregulated the expression of sex-determining region Y-related high-mobility group box transcription factor 4 (SOX4), which is reported to mediate the activation of the AKT pathway, and SOX4 deficiency reversed the cellular functions caused by PLAC8 overexpression. Overall, the present study indicates that PLAC8 may facilitate CC development by activating the SOX4-mediated AKT pathway, suggesting that PLAC8 may serve as a potential biomarker for CC treatment. Graphical abstract
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2026
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IF 3.4
Jingwen Zhang,Xin Jin,Yajiao Sun,Rongyao Xia,Fuhui Chen
Epithelial-mesenchymal transition (EMT)-inducing signals trigger the accumulation of extracellular matrix, thereby contributing to organ pathology, including idiopathic pulmonary fibrosis (IPF). Transcription factor AP-2 alpha (TFAP2A) has been reported to facilitate the EMT process, but its function in IPF remain unknown. A mouse IPF model was established via single intratracheal instillation of bleomycin (BLM). Adenovirus carrying shRNA specifically targeting TFAP2A was administered 24 h prior to BLM challenge to achieve TFAP2A silencing. For in vitro studies, human bronchial epithelial cells (BEAS-2B) underwent lentivirus infection for 48 h to achieve TFAP2A silencing, followed by BLM treatment. We found that the expression of TFAP2A at both mRNA and protein levels was significantly upregulated in fibrotic lung tissue. TFAP2A knockdown alleviated BLM-induced lung injury and fibrosis, as evidenced by reduced collagen deposition and decreased expression of the fibrotic biomarkers α-SMA and Collagen I. Furthermore, TFAP2A silencing inhibited BLM-induced EMT in in the lungs of fibrotic mice, characterized by the upregulation of epithelial markers (Cytokeratin-8 and E-cadherin) and downregulation of mesenchymal markers (Fibronectin, Vimentin, and N-cadherin). In vitro assays demonstrated that BLM exposure increased α-SMA protein expression and promoted the EMT process in BEAS-2B cells, which were reversed by TFAP2A knockdown. Interestingly, TFAP2A significantly upregulated the RNA level of bradykinin receptor B1 (BDKRB1), a fibrosis-inducing factor. Mechanistically, TFAP2A activated BDKRB1 transcription by binding to the promoter of BDKRB1. Overexpression of BDKRB1 abrogated the protective effects of TFAP2A knockdown against lung fibrosis. Overall, our findings demonstrate that TFAP2A drives EMT progression and promotes IPF development by transcriptionally activating BDKRB1, identifying the TFAP2A/BDKRB1 axis as a potential therapeutic target in IPF.
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高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2018
·Vol. 175
·期 15
·3111-3130
·
IF 6.81
Siming Yu,Linna Li,Wei Tian,Dan Nie,Wei Mu,Fang Qiu,Yu Liu,Xinghan Liu,Xiaofeng Wang,Zhimin Du,Wen-Feng Chu,Baofeng Yang
Background and Purpose PEP06, a polypeptide modified from endostatin, was investigated for its antitumour effects on colorectal cancer (CRC) and the possible mechanisms of this antitumour activity were examined in in vitro and in vivo models. Experimental Approach After PEP06 treatment, cell proliferation and migration assays were performed in CRC cells. Epithelial–mesenchymal transition (EMT) progression was determined by Western blotting, immunofluorescent staining and immunohistochemistry in vitro and in a residual xenograft model. MiRNAs regulated by PEP06 were identified by miRNA microarray and verified by in situ hybridization and quantitative real-time PCR. The interactions between PEP06 and integrin αvβ3 were determined with Biacore SA biochips. The cellular function of miR-146b-5p was validated by gain-of-function and loss-of-function approaches. A mouse model of lung metastasis was used to determine the effect of PEP06 on metastatic growth. Key Results PEP06 did not affect cell viability but reduced migration and EMT in SW620 and HCT116 cells. PEP06 significantly repressed the expression of miR-146b-5p in these two cell lines through binding to integrin αvβ3. MiR-146b-5p was shown to increase EMT by targeting Smad4, and the miR-146b-5p-Smad4 cascade regulated EMT in CRC. PEP06 also suppressed CRC pulmonary metastasis, increased survival of mice and hampered residual tumour growth by inhibiting EMT through down-regulating miR-146b-5p. Conclusions and Implications PEP06 is a polypeptide that inhibits the growth and metastasis of colon cancer through its RGD motif binding to integrin αvβ3, thereby down-regulating miR-146b-5p to inhibit EMT in vitro and in vivo . It might have potential as a therapeutic for CRC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2021
·Vol. 53
·期 2
·238-248
·
IF 3.848
Wang Xiaoqiang,Zhang Ruirui,Wu Tong,Shi Yumiao,Zhou Xiao,Tang Dan,Yu Weifeng,So Edmund Cheung,Wu Xiaodan,Pan Zhiying,Tian Jie
Naltrexone is widely used for alleviating opioid-related side effects in cancer patients. However, the effects of naltrexone on cancer progression are controversial in the literature. The present study was carried out to investigate the effects of successive treatment with clinically relevant doses of naltrexone on the malignant biological behaviors of bladder cancer cells. The human bladder cancer T24 cells and mouse bladder cancer MB49 cells were treated with naltrexone. Cell proliferation, migration, and invasion abilities were analyzed. Morphological changes of the cells were confirmed by F-actin immunofluorescence staining. Epithelial–mesenchymal transition (EMT)-related markers and transcriptional factors, as well as activation of the phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway, were analyzed. Results showed that, compared with the control group, successive treatment with naltrexone significantly promoted the proliferation and decreased the apoptosis of bladder cancer cells, together with increase in cell migration and invasion ability. Continuous treatment with naltrexone also significantly reduced the expression of epithelial markers (E-cadherin and cytokeratin 19), increased the expression of mesenchymal markers (N-cadherin and vimentin) and EMT-inducing transcription factors (Snail and Slug), and further shifted the morphological phenotype of bladder cancer cells to a mesenchymal phenotype. The PI3K/AKT signaling pathway was activated by successive treatment with naltrexone. Notably, incubation with the specific PI3K inhibitor LY294002 together with naltrexone reversed the naltrexone-induced EMT progression. In conclusion, successive treatment with naltrexone may be favorable for the progression of bladder tumors by activating the PI3K/AKT signaling pathway and inducing EMT. Long-term exposure to naltrexone should be used cautiously in patients with bladder cancer.
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2019
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IF 3.046
Jianghong Wu,Ziwen Long,Hong Cai,Shengjia Yu,Xiaowen Liu
Aim: To study the carcinogenetic mechanism of HOXB7 in gastric cancer (GC) remains. Methods: Two human GC cell lines — SGC7901 and SNU1 — were used for this study. SGC7901 cells were transfected with siRNA-HOXB7 (siHOXB7) to knock down HOXB7 expression, whereas, SNU1 cells were transduced with pCDNA3.1-HOXB7 to overexpress HOXB7. After transfection, cancer progression was assessed by determining cell proliferation, wound-healing process, cell cycle, apoptosis, invasion, and migration. The effect of HOXB7 on epithelial–mesenchymal transition (EMT) was measured by observing changes in F-actin cytoskeleton and evaluating the expression of EMT markers. p-Scr and p-FAK were evaluated to assess the mechanism. Results: Knockdown of HOXB7 suppressed cell proliferation, alleviated the wound-healing process, inhibited cell migration and invasion, and arrested the cell cycle while promoting cell apoptosis, suggesting the tumor-suppressive effect of siHOXB7 in human GC cells. On the contrary, HOXB7 overexpression showed a tumor-promoting effect on human GC cells. Moreover, we confirmed an inhibitory effect of siHOXB7 on the EMT process by preventing epithelial cells from acquiring a mesenchymal phenotype and downregulating mesenchymal markers (vimentin, β-catenin, N-cadherin, Twist) while upregulating epithelial markers (E-cadherin). Our data revealed that HOXB7 was associated with Src/FAK and favored the activation of the Src–FAK pathway in human GC cells. Conclusion: HOXB7 accelerated the malignancy of GC, by facilitating EMT and regulating the Scr–FAK pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 46
·期 11
·1900-1914
·
IF 4.473
Bin Xie,Feng Peng,Fengping He,Yixing Cheng,Jiangtao Cheng,Zhibing Zhou,Wei Mao
Ras-association domain family 1A (RASSF1A) is one of the most methylated genes in lung cancer (LC). We investigate whether the high DNA methylation level of RASSF1A can relieve the resistance of RASSF1A to LC by inhibiting RASSF1A's transcription factor binding to RASSF1A. RASSF1A expression in tissues and cells was tested utilizing quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. RASSF1A expression and RASSF1A methylation level in LC cells exposed to 5-Aza-dc were assessed by qRT-PCR and quantitative methylation-specific PCR. The association between CTCF and RASSF1A was assessed using hTFtarget, ChIP, and luciferase reporter gene analysis. The effects of 5-Aza-dc, CTCF, and RASSF1A on cell biological behaviors and epithelial-mesenchymal transition (EMT)-related markers were assessed by cell function experiments and Western blot. Moreover, we constructed the xenograft tumor and pulmonary nodule metastasis models, and assessed tumor volume and weight. RASSF1A expression and pulmonary nodule metastasis were tested utilizing qRT-PCR, Western blot, and H&E staining. RASSF1A was under-expressed in LC tissues and cells. 5-Aza-dc enhanced RASSF1A level and weakened RASSF1A methylation level in LC cells. RASSF1A silencing neutralized 5-Aza-dc-mediated repressing effects on LC cell biological function and EMT. The loss of CTCF binding to RASSF1A in LC cells was associated with DNA methylation. The effect of 5-Aza-dc on RASSF1A level, LC cell malignant behaviors, and EMT-related factors were strengthened by CTCF upregulation. RASSF1A overexpression suppressed LC tumor growth and pulmonary nodule metastasis in vivo. DNA methylation blocked the modulation of RASSF1A expression by CTCF and relieved the resistance of RASSF1A to LC.
研究领域:
癌症生物学
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
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IF 5.6
Jianping Hu,Jinhu Chen,Caili Zhao,Pei Yu,Wenjun Xu,Yong Yin,Lei Yang,Zhenzhen Zhang,Lingyi Kong,Chao Zhang
Osteosarcoma, the most prevalent malignant bone tumor in adolescents, is characterized by its aggressiveness and tendency to metastasize. Despite the advancements in treatment that have improved survival rates for localized cases, metastatic osteosarcoma remains challenging to treat due to the limited efficacy of current therapies and the severe side effects of chemotherapy. Epithelial-mesenchymal transition (EMT) is a key factor in osteosarcoma metastasis, and the miR-194/215 cluster, which is upregulated in osteosarcoma, promotes this process. This study sought to investigate natural compounds that could counteract the miR-194/215 cluster’s effects and inhibit osteosarcoma metastasis. By analyzing miRNA databases and clinical data, a signature gene set for the miR-194/215 cluster was established, and the LINCS database was screened to find natural compounds with antagonistic effects. Icariside II, an active component of Epimedium, was identified as a potential inhibitor and was shown to reduce the migration and invasion of osteosarcoma cells in vitro and lung metastasis in vivo . The study utilized various techniques, including Gene Set Enrichment Analysis (GSEA), Drug Affinity Responsive Target Stability (DARTS), Cellular Thermal Shift Assay (CETSA), molecular docking, and enzyme activity assays, to identify phosphoglycerate kinase 1 (PGK1) as the target protein of Icariside II. It was found that Icariside II competitively inhibits PGK1 by binding to its ADP binding pocket, reducing its activity and thus antagonizing the miR-194/215 cluster’s promotion of EMT in metastatic osteosarcoma. The results suggest that Icariside II could be a promising therapeutic agent for metastatic osteosarcoma, providing new targets and strategies for clinical treatment.
研究领域:
肿瘤学
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分子生物学
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药理学
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天然产物化学
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DOI
PubMed
高影响因子
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
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2026
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IF 6.4
Lili Yu,Zhonghua Li,Huawei Xin,Na Shen,Tao Yan,Yulei Cui
Euphorbia helioscopia L. is a traditional medicinal plant, whose seeds (EHS) are often discarded as agricultural waste. This study aimed to explore the metabolic profile and anti-epithelial-mesenchymal transition (EMT) potential of EHS compared with the conventional whole herb (EHQ). Using UPLC-ESI-MS/MS-based widely targeted metabolomics, 2178 metabolites were identified, with 1423 showing differential accumulation between EHQ and EHS. EHQ was rich in flavonoids, while EHS relatively enriched in lipids compared to EHQ metabolome, enriched in fatty acids such as octanoic, stearic, and octadecenoic acids. Pathway analysis highlighted disparities in lipid and flavonoid biosynthesis. In vitro assays on A549 lung cancer cells revealed that EHS extract possessed stronger cytotoxicity (IC 50 = 0.80 mg/mL) and more potently inhibited cell migration and EMT progression, evidenced by upregulated E-cadherin and downregulated N-cadherin and α-SMA. These findings position EHS as a promising candidate contributors’ lipid-rich resource for anti-EMT drug development, advocating for the valorization of underutilized plant parts in sustainable bioproduct pipelines.
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高影响因子
Reproductive Sciences
·
2025
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IF 2.5
Qiu Yingying,Wei Xinjun,Cao Jian,Wang Jindan,Dou Qianru,Zhou Fangfang,Chen Xi,Liu Yongli,Wan Guiping,Huang Meihua,Li Zhenli,Gui Tao
Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial–mesenchymal transition (EMT) is a key driver of AM progression. In this study, we investigated the role and underlying mechanisms of endometrial mesenchymal stem cell (eMSC)-derived exosomes in regulating AAM polarization and the subsequent EMT of endometrial epithelial cells (EECs). In vitro coculture studies revealed that AM eutopic eMSCs markedly induced M2 macrophage polarization via exosomes and promoted EMT of EECs. Differentially expressed microRNAs (DE-miRNAs) between exosomes derived from normal eMSCs (N-eMSCs) and AM eutopic eMSCs (A-eMSCs) were identified using miRNA sequencing and miR-4669 was found to be the most significantly upregulated miRNA. Internalization of exosomal miR-4669 by macrophages induced their polarization toward the M2 phenotype and promoted the EMT of EECs. Mechanistic analysis using luciferase assay, mRNA sequencing, and rescue experiments revealed that miR-4669 induced M2 macrophage polarization via downregulation of DUSP6 and activation of MAPK/ERK signaling. The polarized M2 macrophages promoted the EMT of ISK cells via TGF-β1 secretion. In an AM xenograft mouse model, miR-4669 depletion inhibited AM progression by targeting the DUSP6/ERK1/2 pathway in macrophages. Overall, AM A-eMSC-derived exosomal miR-4669 facilitates M2 macrophage polarization by targeting the DUSP6/ERK signaling pathway, thereby promoting EMT of EECs via TGF-β1 secretion. These findings open avenues for developing novel preventive and therapeutic strategies for AM. Graphical
研究领域:
妇科学
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干细胞生物学
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分子生物学
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细胞信号传导
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癌症生物学
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免疫学
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microRNA研究
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PubMed
高影响因子
危险品化学品经营许可证（带存储）