Bioengineered
·
2020
·
IF 2.205
Bing Han,Yang Ge,Junpeng Cui,Baolin Liu
Long non-coding RNAs (lncRNAs) play a key role in the development and metastasis of cancer. However, the biological role and clinical significance of lncRNA DNAJC3-AS1 in the development of colon cancer is still unknown. In this study, the effects of DNAJC3-AS1 on cell proliferation, migration, and invasion were evaluated by MTT assay, wound-healing assay, and transwell assay, respectively. The relationship between DNAJC3-AS1, miR-214-3p and LIVIN was predicted by the online software and confirmed by dual-luciferase reporter assay. We found that the down-regulation of DNAJC3-AS1 inhibited the proliferation of colon cancer cells and induced growth arrest. Down-regulation of DNAJC3-AS1 also inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of colon cancer cells. Moreover, miR-214-3p can bind to DNAJC3-AS1, and knockdown of DNAJC3-AS1 increased miR-214-3p expression in colon cancer cells. LIVIN was identified as a target of miR-214-3p. The up-regulation of miR-214-3p inhibited the protein expression of LIVIN and suppressed the activation of the NF-κB signaling pathway. Besides, down-regulation of DNAJC3-AS1 reduced cell viability, invasion, and EMT of colon cancer cells, while miR-214-3p inhibitor could reverse these effects. The expression of LIVIN and the activation of the NF-κB signaling pathway were suppressed by down-regulating DNAJC3-AS1, while these effects could be restored by miR-214-3p inhibitor. These findings suggested that DNAJC3-AS1 may promote colon cancer progression by regulating the miR-214-3p/LIVIN axis. DNAJC3-AS1 may serve as a new biomarker and therapeutic target for colon cancer, stimulating new research directions and treatment options.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DIGESTIVE DISEASES AND SCIENCES
·
2022
·Vol. 67
·期 10
·4780-4796
·
IF 3.487
Duan Houyu,Ding Xiang,Luo Hesheng
Background and Aims KISS-1 is an established tumor suppressor that inhibits metastases in various malignancies. However, little is known regarding its role in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to identify the possible mechanisms of KISS-1 in ESCC metastasis. Methods The expression levels of KISS-1 mRNA and protein in ESCC samples and cell lines were analyzed by qRT-PCR, IHC, and western blotting. Bisulfite sequencing PCR (BSP) and methylation-specific PCR (MSP) were used to analyze the methylation pattern of KISS-1 promoter in ESCC cells with or without 5-Aza-dC treatment. The role of KISS-1 in the progression and metastasis of ESCC was analyzed through in vitro functional assays. Results KISS-1 mRNA and protein were markedly downregulated in ESCC tissues and cell lines compared to the respective controls. Hypermethylation of KISS-1 promoter correlated to its lower expression levels in ESCC, and KISS-1 demethylation inhibited tumor progression. Ectopic KISS-1 overexpression inhibited tumor cell metastasis in vitro. In addition, KISS-1 overexpression downregulated the matrix metalloproteinase 2 and 9 (MMP2 and 9) and inhibited epithelial–mesenchymal transition (EMT). Finally, KISS-1 downregulated phosphorylated extracellular regulated protein kinase 1/2 (ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (MAPK) without affecting their total expression levels in the ESCC cells. MAPK/ERK and p38 MAPK agonists reversed the suppressive effects of KISS-1. Conclusions The hypermethylation of KISS-1 promoter partly contributed to its downregulation in ESCC. KISS-1 inhibits the metastasis of ESCC cells by targeting the MMP2/9/ERK/p38 MAPK axis.
研究领域:
肿瘤学
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分子生物学
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癌症遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL CYCLE
·
2023
·
IF 4.3
Huizhi Wang,Yuntao Ding,Qiuming Zhu,Zhengyue Yu,Qi Wang,Aihua Gong,Min Xu
Background Long non-coding RNAs (lncRNAs) have been proved to play a vital role in pancreatic cancer (PC). However, the role of lncRNA FAM83A-AS1 in PC remains unclear. In this study, we explored the biological function and underlying mechanism of FAM83A-AS1 in PC cells.Methods The FAM83A-AS1 expression was assessed via public databases and validated by qRT-PCR. The biofunction and immune cell infiltration of FAM83A-AS1 were analyzed through GO, KEGG, GESA and ssGSEA. The migration, invasion and proliferation abilities of PC cells were examined by Transwell, wound healing, CCK8 and colony formation. The EMT and Hippo pathway markers were evaluated by western blot.Results FAM83A-AS1 expression was higher in PC tissues and cells than normal. Additionally, FAM83A-AS1 was associated with poor prognosis of PC and involved in cadherin binding and immune infiltration. Subsequently, we proved FAM83A-AS1 overexpression enhanced the migration, invasion and proliferation abilities of PC cells, whereas FAM83A-AS1 downregulation inhibited those. Moreover, western blot results showed that FAM83A-AS1 knockdown increased the E-cadherin expression and decreased the expression of N-cadherin, β-catenin, Vimentin, Snail and Slug. On the contrary, FAM83A-AS1 upregulation results in the opposite effects. Besides, FAM83A-AS1 overexpression inhibited the expression of p-YAP, p-MOB1, p-Lats1, SAV1, MST1 and MST2 as well as the results of FAM83A-AS1 knockdown were opposite.Conclusion FAM83A-AS1 promoted EMT of PC cells via Hippo signaling inactivation and may be a potential diagnosis and prognosis target.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Shuanghui Lu,Xiu Chen,Yujia Chen,Yingqiong Zhang,Jun Luo,Huidi Jiang,Luo Fang,Hui Zhou
Transforming growth factor-beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of renal tubular cells promotes renal fibrosis and the progression of chronic kidney disease (CKD). PDZ domain-containing 1 (PDZK1) is highly expressed in renal tubular epithelial cells; however, its role in TGF-β1-induced EMT remains poorly understood. The present study showed that PDZK1 expression was extremely downregulated in fibrotic mouse kidneys and its negative correlation with TGF-β1 expression and the degree of renal fibrosis. In addition, TGF-β1 downregulated the mRNA expression of PDZK1 in a time- and concentration-dependent manner in vitro . The downregulation of PDZK1 exacerbated TGF-β1-induced EMT upon oxidative stress, while the overexpression of PDZK1 had the converse effect. Subsequent investigations demonstrated that TGF-β1 downregulated PDZK1 expression via p38 MAPK or PI3K/AKT signaling in vitro , but independently of ERK/JNK MAPK signaling. Meanwhile, inhibition of the p38/JNK MAPK or PI3K/AKT signaling using chemical inhibitors restored the PDZK1 expression, mitigated renal fibrosis, and elevated renal levels of endogenous antioxidants carnitine and ergothioneine in adenine-induced CKD mice. These findings provide the first evidence suggesting a negative correlation between PDZK1 and renal fibrosis, and identifying PDZK1 as a novel suppressor of renal fibrosis in CKD through ameliorating oxidant stress.
研究领域:
肾病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Ying Zhang,Changjun Yin,Chao Wei,Shuai Xia,Zhu Qiao,Xue-Wen Zhang,Bin Yu,Jun Zhou,Rong Wang
Migration, invasion, epithelial-mesenchymal transformation (EMT), and chemotherapeutic resistance are the leading causes of therapeutic failure in people with colorectal cancer (CRC). The migration of exosomal miRNA between cancer cells and the tumor microenvironment is directly associated with malignant behavior in cancer-associated fibroblasts (CAFs). In the context of earlier research, the purpose of the current study was to assess the role and potential mechanism of miR-625-3p released by CAFs in CRC cells. Exosomes were extracted and purified from CAFs conditioned medium by ultracentrifugation. Western blot , immunohistochemistry, CCK-8, transwell assay, H&E staining, Tunnel, real-time PCR, double luciferase assay, RNA-binding protein immunoprecipitation (RIP), and immunofluorescence double staining experiments were used to investigate the effects of CAFs-Exo and miR-625-3p on CRC cell invasion, migration, proliferation, EMT, chemotherapeutic resistance, and molecular mechanisms. The current results indicated that CAFs-Exo was directly internalized by CRC cells, and exosomal miR-625-3p derived from CAFs might promote migration, invasion, EMT and chemotherapeutic resistance in CRC cells by inhibiting the CELF2/WWOX pathway, providing a potential candidate for CRC prediction and treatment.
研究领域:
肿瘤学
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分子生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2023
·
IF 3.7
Lirong Zou,Xinling Wang,Xiao Han
The retina may undergo structural and functional damage as a result of hypoxia, which could lead to permanent blindness. As competing endogenous RNAs (ceRNAs), lncRNAs are essential in eye disorders. The biological function of lncRNA MALAT 1 and its potential mechanisms in hypoxic-ischemic retinal diseases are still unknown. MALAT 1 and miR-625–3p expression alterations in hypoxia-treated RPE cells were examined using qRT-PCR. The target binding relationships between MALAT 1 and miR-625–3p, as well as between miR-625–3p and HIF-1α, were identified utilizing bioinformatics analysis and dual luciferase reporter assay. We observed that si-MALAT 1 and miR-625–3p mimic both reduced apoptosis and epithelial-mesenchymal transition (EMT) in hypoxic RPE cells, whereas si-MALAT 1 was reversed by miR-625–3p inhibitor. Further, we carried out a mechanistic investigation, and rescue assays demonstrated that MALAT 1 sponging miR-625–3p influenced HIF-1α expression and consequently took part in the NF-κB/Snail signaling pathway , which regulated apoptosis and EMT. In conclusion, our research had shown that the MALAT 1/miR-625–3p/HIF-1α axis drove the progression of hypoxic-ischemic retinal disorders and may serve as a promising predictive biomarker for their therapeutic and diagnostic targets.
研究领域:
眼科学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2017
·Vol. 15
·期 1
·1362-1372
·
IF 1.39
Chun‑Yu Li,Qi Wang,Shen Shen,Xiao‑Lu Wei,Guo‑Xia Li
Epithelial‑mesenchymal transition (EMT) has been reported to play pivotal roles in tumor invasion and metastasis. Inhibition of EMT may exert beneficial effects in regulating metastasis. Oridonin (ORI), an active diterpenoid compound isolated from Rabdosia rubescens, was found to be a potent anti‑metastatic agent. However, the possible involvement of ORI in the EMT in malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16‑F10 melanoma cells. The transforming growth factor‑β1 (TGF‑β1)‑induced EMT was also inhibited in ORI‑treated cells, as reflected in the upregulation of E‑cadherin, and downregulation of vimentin and Snail. Similar results were observed in A375 and B16‑F10 melanoma cells treated with ORI. Furthermore, pre‑treatment with ORI blocked the TGF‑β1‑induced phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt)/glycogen synthase kinase (GSK)‑3β signaling pathway activation. These effects mimicked PI3 kinase inhibitor LY294002 treatment. ORI interfered with the PI3K/Akt/GSK‑3β pathway, and reversed TGF‑β1‑induced EMT, which suppressed the invasion and metastasis of melanoma cells. Taken together, the present study demonstrated that ORI inhibits melanoma cells migration, invasion, and adhesion and TGF‑β1‑induced EMT through the PI3K/Akt/GSK‑3β signaling pathway. These findings suggest that ORI is a promising anti‑metastasis agent for melanoma.
研究领域:
肿瘤学
·
细胞生物学
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分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 28
·6951-6962
·
IF 4.157
Wang Huai-Song,Xia Xingya,Wang Yingming,Lyu Weiping,Sang Mangmang,Gu Congcong,Liu Wenyuan,Zheng Feng
Epithelial-mesenchymal transition (EMT) is implicated in the pathological processes of cancer metastasis and drug resistance. Anti-cancer drugs may also potentially lead to EMT, resulting in their reduced therapeutic effect. Therefore, the combination of these anti-cancer drugs with anti-EMT agents has been promoted in clinic. Screening anti-EMT drugs and evaluation of EMT process are highly dependent on EMT biomarkers on cell membrane. At present, the detection of EMT biomarker is mainly by Western blot method, which is time-consuming and complicated. In this work, for effectively screening anti-EMT drugs by evaluation of the EMT process, a type of aptamer probe based on aggregation-induced emission (AIE) was designed. The aptamer SYL3C was employed to target the EMT biomarker EpCAM on cell membrane. Two fluorophores, FAM and tetraphenylethene (TPE, an AIE dye), were modified at the two ends of SYL3C, respectively. This aptamer probe (TPE-SYL3C-FAM) can monitor the EpCAM expression, which can be recovered by anti-EMT drugs. By observation of the change in TPE emission intensity, the anti-EMT effect of drugs can be evaluated. The FAM emission was used as internal reference to reduce environmental interferences. This probe can be potentially used to screen anti-EMT agents as anti-cancer adjuvant drugs with high throughput. Graphical abstract
研究领域:
肿瘤学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2024
·Vol. 28
·期 3
·1-11
·
IF 2.5
Weimin Hu,Ling Cheng,Jian Zhao,Yonghui Wu,Ying Lin,Jun Yin
Transforming growth factor‑β (TGF‑β) signaling pathway serves a pivotal role in the pathogenesis of colorectal cancer (CRC). However, the specific molecular mechanisms by which the TGF‑β signaling pathway regulates CRC are still not fully understood. In the present study, metabolomics and transcriptomics were used to screen for key metabolites and regulatory genes most related to the regulation of the TGF‑β signaling pathway in CRC. Additionally, reverse transcription‑quantitative PCR, western blotting and Transwell assays were performed to assess the process of epithelial‑mesenchymal transition (EMT). Metabolomics analysis indicated that TGF‑β1 has an impact on purine metabolism, leading to an increase in the purine metabolite inosine. The increase of inosine is essential for facilitating EMT and cell migration in CRC cells. Furthermore, the integrated analysis of metabolomics and transcriptomics data revealed that TGF‑β1 induces the expression of laccase domain‑containing 1 (LACC1), an enzyme involved in the regulation of inosine. Knockdown of LACC1 resulted in a reduction of TGF‑β1‑induced alterations in inosine levels, EMT and cell migration in CRC cells. The results of the present study suggest that the TGF‑β signaling pathway is involved in the regulation of purine metabolism in CRC through the modulation of LACC1 expression. Furthermore, LACC1 appears to influence EMT and cell migration by elevating the levels of the purine metabolite inosine.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Translational Oncology
·
2024
·
IF 4.5
Wei An,Kai Zhang,Guangbing Li,Shunzhen Zheng,Yukun Cao,Jun Liu
Cholangiocarcinoma remains a challenging primary hepatobiliary malignancy with dismal prognosis. Photodynamic therapy (PDT),a less invasive treatment, has been found to inhibit the proliferation and induce ferroptosis, apoptosis and necrosis in other tumor cells in recent years. Regrettably, the role and exact molecule mechanism of PDT is still incompletely clear in cholangiocarcinoma cells. Ferroptosis is a novel regulated cell death(RCD), which is controlled by glutathione peroxidase4(GPX4) with the characteristics of iron dependent and excessive intracellular accumulation of lipid peroxides. This novel form of RCD has attracted great attention as a potential new target in clinical oncology during recent years. In this study, we observed that hypericin mediated PDT(HY-PDT) could significantly inhibit the proliferation of the cholangiocarcinoma cells and suppress migration and the epithelial mesenchymal transition (EMT) as well. Then, we conducted transcriptome sequencing and bioinformatics analysis and observed that HY-PDT was most likely involved in ferroptosis, apoptosis, the EMT process and AKT/mTORC1 signaling pathways in cholangiocarcinoma cells. Next, a series of in vitro and in vivo experiments were performed to confirm that HY-PDT could trigger cholangiocarcinoma cells ferroptosis through inhibiting the expression of GPX4 protein. In terms of molecular mechanism, we found that HY-PDT induced ferroptosis by decreasing GPX4 expression via suppression of the AKT/mTORC1 signaling pathway. In addition, we also found that HY-PDT inhibit cholangiocarcinoma cells migration and the EMT process by inhibiting the AKT/mTORC1 pathway. Our study illustrated a new mechanism of action for HY-PDT and might throw light on the individualized precision therapy for cholangiocarcinoma patients.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Xiuchun Li,Shanshan Yan,Jing Dai,Yi Lu,Yiqun Wang,Man Sun,Jinkang Gong,Yuan Yao
Epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell–cell contact to become mesenchymal stem cells, which is important on development and embryogenesis, wound healing, and cancer metastasis. This research aims to investigate the effect of topological cue as modulating factor on the EMT by tuning the diameter of electrospinning nanofiber. The cell-nanofiber interaction between human lung epithelial cell A549 and electrospinning nanofibers composed of polyvinyl alcohol (PVA) and type I collagen were investigated. The electrospinning of regenerated PVA/Collagen nanofibers were performed with water/acetic acid as a spinning solvent and glutaraldehyde as a chemical cross-linker. Parameterization on concentration, applied voltage and feeding rate was finalized to generate smooth nanofibers with good homogeneity. The scanning electron microscopy result demonstrated that A549 cell appropriately achieved extended morphology by the filopodia attaching to the surface of the nanofibrous mats. When the diameter changed from 90 nm to 240 nm, the A549 cell was correspondingly express varied EMT related genes. Gene expression analysis was conducted by qPCR using three typical markers for detecting EMT: N-cadherin (NCad), Vimentin (Vim), and Fibronectin (Fib) . An increasing expression pattern was observed on cell culturing on 170 nm sample with respect to cell cultured on 90 nm and 240 nm. This result indicated the 170 nm PVA/Collagen nanofibers induce A549 cells to process epithelial–mesenchymal transition more seriously than those on 90 nm or 240 nm.
研究领域:
生物材料
·
细胞生物学
·
组织工程
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Xiaoxiao Xu,Chuang Ma,Hang Wu,Yuanqiao Ma,Zejin Liu,Peijie Zhong,Chaolei Jin,Wenjuan Ning,Xiao Wu,Yijie Zhang,Jichang Han,Junpeng Wang
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
研究领域:
肺科学
·
细胞生物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）