PDF(2746 KB)
缺氧抑制因子ZNF92在肝癌生长和侵袭中的功能研究
李婷婷, 张婷, 张亚楠, 刘婕, 丁丽华, 叶棋浓
中国生物工程杂志 ›› 2024, Vol. 44 ›› Issue (11) : 20-29.
PDF(2746 KB)
PDF(2746 KB)
缺氧抑制因子ZNF92在肝癌生长和侵袭中的功能研究
Functional Study of Hypoxia-inhibitory Factor ZNF92 in the Growth and Invasion of Hepatocellular Carcinoma
({{custom_author.role_en}}), {{javascript:window.custom_author_en_index++;}}目的:探究缺氧调控因子锌指蛋白92(zinc finger proteins 92,ZNF92)在肝细胞癌生长和侵袭中发挥的功能及其可能的调控机制。方法:(1)利用RNA-seq筛选出缺氧抑制因子ZNF92并通过RT-qPCR和Western blot检测缺氧环境(1% O2)对ZNF92的mRNA表达水平和蛋白质表达水平的影响。(2)利用慢病毒载体构建敲低ZNF92基因的肝癌细胞系。(3)通过CCK-8实验、划痕试验和Transwell实验确定ZNF92基因对肝癌细胞HepG2、SMMC7721生长和侵袭的影响。(4)通过在敲低ZNF92基因的稳定肝癌细胞系中瞬时转染锌指E盒结合同源盒1 (zinc finger E-box binding homeobox,ZEB1)的siRNA,通过Western blot确定ZEB1转染成功,并在该细胞系中检测ZNF92能否通过调控ZEB1的表达调控上皮间充质转化(epithelial-mesenchymal transition,EMT)进程。(5)通过在敲低ZNF92基因的稳定肝癌细胞系中瞬时转染缺氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)的siRNA,检测ZNF92是否可能通过HIF-1α影响细胞迁移和侵袭。结果:(1)缺氧抑制ZNF92的mRNA表达和蛋白质表达。(2)ZNF92调控EMT的关键转录因子ZEB1的蛋白质表达影响EMT进程。(3)ZNF92抑制肝癌细胞迁移和侵袭,但不影响肝癌细胞增殖。(4)ZNF92通过ZEB1部分调控肝癌细胞迁移和侵袭。(5)ZNF92可能通过HIF-1α调控ZEB1以影响肝癌细胞迁移和侵袭。结论:新缺氧抑制因子ZNF92可能通过HIF-1α影响EMT进程,进而通过调控ZEB1影响肝癌细胞的迁移和侵袭。
Objective: To investigate the function and mechanism of the hypoxia-regulated factor zinc finger proteins 92 (ZNF92) in hepatocellular carcinoma cell growth and invasion. Methods: (1) The mRNA and protein expression levels of ZNF92 were detected by RT-qPCR and Western blot. (2) ZNF92 knockdown hepatocellular carcinoma cell line was established using lentiviral vectors. (3) The effects of ZNF92 on hepatocellular carcinoma HepG2 cells, and SMMC7721 cell growth and invasion in vitro were evaluated by CCK-8, scratch and transwell assays. (4) Small interfering RNA (siRNA) was used to determine the knockdown of ZEB1 expression and to determine whether ZNF92 indirectly regulates the epithelial-mesenchymal transition (EMT) process through ZEB1. (5) siRNA was used to determine the knockdown of HIF-1α and to detect the changes in cell migration and invasive ability. Results: (1) Hypoxia inhibited the mRNA and protein expression of ZNF92. (2) ZNF92 regulates the protein expression of zinc finger E-box binding homeobox 1 (ZEB1), a key transcription factor of EMT, thereby affecting the EMT process. (3) ZNF92 inhibits hepatocellular carcinoma migration and invasion without affecting the proliferation process. (4) ZNF92 partially regulates migration and invasion of hepatocellular carcinoma cells through ZEB1. (5) ZNF92 may partially regulate ZEB1 through HIF-1α to affect the migration and invasion of hepatocellular carcinoma cells. Conclusions: The novel hypoxia-inhibitory factor ZNF92 may affect the EMT process through HIF-1α, and then affect the migration and invasion of hepatocellular carcinoma cells by regulating ZEB1.
肿瘤缺氧 / 锌指蛋白92 / 缺氧诱导因子1α / 锌指E盒结合同源盒1 {{custom_keyword}} /
Hypoxia of tumors / ZNF92 / HIF-1α / ZEB1 {{custom_keyword}} /
图1 以1% O2浓度缺氧处理12 h、24 h后肝癌细胞中ZNF92的mRNA表达与蛋白质表达A: 实时荧光定量PCR,检测肝癌细胞HepG2与SMMC7721以1% O2浓度培养12 h、24 h后ZNF92的mRNA表达变化 (** P<0.01,*** P<0.001) B: 蛋白质印迹,检测肝癌细胞HepG2与SMMC7721细胞以1% O2浓度培养12 h、24 h后ZNF92的蛋白质表达变化 Fig.1 mRNA expression and protein expression of ZNF92 in hepatocellular carcinoma cells after hypoxia treatment with 1% oxygen concentration for 12 h and 24 h A: Determination of ZNF92 mRNA expression in hepatocellular carcinoma cells HepG2 and SMMC7721 after 12 h and 24 h of incubation in an anoxic incubator with 1% O2 (** P<0.01,*** P<0.001) B: Determination of ZNF92 protein expression in hepatocellular carcinoma cells HepG2 and SMMC7721 cultured in an anoxic incubator with 1% O2 for 12 h and 24 h |
图2 敲低ZNF92后肝癌细胞ZEB1、SLUG的蛋白表达变化A: 蛋白质印迹检测肝癌细胞HepG2与SMMC7721敲低细胞系中SLUG、ZEB1蛋白表达变化 B:相对蛋白质表达量统计分析 (** P<0.01) Fig.2 Detect changes in ZEB1 and SLUG protein expression by knocking down ZNF92 in hepatocellular carcinoma cells A: Protein immunoblotting to detect changes in protein expression of SLUG, ZEB1 in hepatocellular carcinoma cells HepG2 with SMMC7721 knockdown cell line B:Statistical analyses of relative protein expression (** P< 0.01) |
图3 敲低ZNF92对肝癌细胞迁移、侵袭和增殖能力的影响A: 细胞划痕试验,在HepG2、SMMC7721细胞中敲低ZNF92并进行回补,检测细胞迁移情况,迁移的统计分析显示在右侧。比例尺:100 μm (* P<0.05,** P<0.01) B:细胞侵袭实验,在HepG2、SMMC7721细胞中敲低ZNF92并进行回补,检测细胞侵袭情况,侵袭的统计分析显示在右侧。比例尺:100 μm (* P<0.05) C: 细胞增殖曲线测定,在HepG2、SMMC7721细胞中敲低ZNF92并进行回补,检测细胞增殖情况 Fig.3 Effect of knockdown of ZNF92 on migration, invasion and proliferation ability of hepatocellular carcinoma cells A: ZNF92 knockdown and post-knockdown supplementation in HepG2 and SMMC7721 cells to detect cell migration, statistical chart on the right. Scale bar: 100 μm (* P<0.05,** P<0.01) B: ZNF92 knockdown and post-knockdown supplementation in HepG2 and SMMC7721 cells to detect cell invasion, statistical chart on the right. Scale bar: 100 μm (* P<0.05) C: ZNF92 knockdown and post-knockdown supplementation in HepG2 and SMMC7721 cells to detect cell proliferation |
图4 ZNF92基因稳定敲低的肝癌细胞株中瞬时转染ZEB1 siRNA 后肝癌细胞迁移、侵袭能力的变化A: 细胞划痕试验,在敲低ZNF92的HepG2、SMMC7721细胞中瞬时转染ZEB1 siRNA,检测细胞迁移情况,迁移的统计分析显示在右侧。比例尺:100 μm (* P<0.05,** P<0.01) B: 细胞侵袭实验,在敲低ZNF92的HepG2、SMMC7721细胞中瞬时转染ZEB1 siRNA,检测细胞侵袭情况,侵袭的统计分析显示在右侧。比例尺:100 μm (* P<0.05) C: 蛋白质印迹,检测敲低ZNF92的HepG2、SMMC7721细胞中E-cadherin、N-cadherin和Vimentin的蛋白质表达变化(左)及转染ZEB1 siRNA后ZEB1、ZNF92蛋白表达(右) Fig.4 Changes in the migration and invasion ability of hepatoma cells after transient transfection of ZEB1 siRNA in hepatoma cell lines with stable knockdown of ZNF92 gene A: Transient transfection of ZEB1 siRNA in HepG2, SMMC7721 cell lines knocked down for ZNF92 and detection of cell migration ability, statistical chart on the right. Scale bar: 100 μm (* P<0.05,** P<0.01) B: Transient transfection of ZEB1 siRNA in HepG2, SMMC7721 cell lines knocked down for ZNF92 and detection of cell invasion, statistical chart on the right. Scale bar: 100 μm (* P<0.05) C: Detection of protein expression changes of E-cadherin, N-cadherin and Vimentin in HepG2 and SMMC7721 cells with knockdown of ZNF92 (left) and ZEB1 and ZNF92 protein expression after transfection with ZEB1 siRNA (right) |
图5 ZNF92基因稳定敲低的肝癌细胞株中瞬时转染HIF-1α siRNA 后肝癌细胞迁移、侵袭能力的变化A: 细胞划痕试验,在敲低ZNF92的HepG2、SMMC7721细胞中瞬时转染HIF-1α siRNA,检测细胞迁移情况,迁移的统计分析显示在右侧。比例尺:100 μm (** P<0.01) B: 细胞侵袭实验,在敲低ZNF92的HepG2、SMMC7721细胞中瞬时转染HIF-1α siRNA,检测细胞侵袭情况,侵袭的统计分析显示在右侧。比例尺:100 μm (* P<0.05) Fig.5 Changes in the migration and invasion ability of hepatoma cells after transient transfection of HIF-1α siRNA in hepatoma cell lines with stable knockdown of ZNF92 gene A: Transient transfection of HIF-1α siRNA in HepG2, SMMC7721 cell lines knocked down for ZNF92 and detection of cell migration ability, statistical chart on the right. Scale bar: 100 μm (** P<0.01) B: Transient transfection of HIF-1α siRNA in HepG2, SMMC7721 cell lines knocked down for ZNF92 and detection of cell invasion, statistical chart on the right. Scale bar: 100 μm (* P<0.05) |
| [1] |
Choriocarcinoma (CC) is the highest malignant gestational trophoblastic tumor which causes high mortality without timely treatment. HIF-1α is a very important molecule promoting neoplasm aggressiveness, metastasis through the induction of the epithelial to mesenchymal transition (EMT). Several researches have shown that Notch signaling is necessary for coupling hypoxia to the EMT. However, the pathway in choriocarcinoma remains undetermined. In this study, overexpression of HIF-1α inhibited epithelial index E-cadherin, cytokeratin 18 (CK18) and cytokeratin 19 (CK19) in two choriocarcinoma cell lines (JAR and JEG-3, respectively). The reciprocal changes associated with the EMT phenotypic transformation. The migration and invasive capability was significantly enhanced. HIF-1α overexpression was positively correlated with Notch1 and Hes1 (P<0.01; respectively). Using DAPT (Notch1 inhibitor) to knock down Notch1 expression, morphological and molecular typical changes of the EMT were detected in vitro. Knockdown of Notch1 prominently reduced MMP2 and MMP9 activities, and increased E-cadherin, CK18 and CK19 expression in JAR and JEG-3 cells (P<0.01). In vivo, serum-free suspension containing 5x106 JAR cells (lv-HIF-1α and lv-NC, respecticely) were implanted subcutaneously or injected intravenously into female NOD SCID mice, which were injected with DAPT or DMSO six times at 3-day intervals. Mice with subcutaneous nodules were injected i.v. fluorine-18 fluorodeoxyglucose (18F-FDG) and then scanned in small animal PET/CT (SA-PET/CT), and mice with lung metastasis were monitored by using the in vivo imaging system (IVIS). The in vivo data showed that inhibition of Notch signaling by DAPT treatment effectively suppressed metastatic tumor growth, metabolic activity and invasion. In summary, overexpression of HIF-1α promotes choriocarcinoma cell aggressiveness and metastasis through the regulation of the EMT dependenting on Notch signaling pathway.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [2] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [3] |
Glioblastoma (GBM) is the most common brain tumor in adults and the mesenchymal GBM subtype was reported to be the most malignant, presenting severe hypoxia and necrosis. Here, we investigated the possible role of a hypoxic microenvironment for inducing a mesenchymal and invasive phenotype. The exposure of non-mesenchymal SNB75 and U87 cells to hypoxia induced a strong change in cell morphology that was accompanied by enhanced invasive capacity and the acquisition of mesenchymal marker expression. Further analyses showed the induction of HIF1α and HIF2α by hypoxia and exposure to digoxin, a cardiac glycoside known to inhibit HIF1/2 expression, was able to prevent hypoxia-induced mesenchymal transition. ShRNA-mediated knockdown of HIF1α, and not HIF2α, prevented this transition, as well as the knockdown of the EMT transcription factor ZEB1. We provide further evidence for a hypoxia-induced mesenchymal shift in GBM primary material by showing co-localization of GLUT1, ZEB1 and the mesenchymal marker YKL40 in hypoxic regions of the tumor. Collectively, our results identify a HIF1α-ZEB1 signaling axis that promotes hypoxia induced mesenchymal shift and invasion in GBM in a cell line dependent fashion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [4] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [5] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [6] |
C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein-protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.© 2016 Schmitges et al.; Published by Cold Spring Harbor Laboratory Press.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [7] |
The 7S particle of Xenopus laevis oocytes contains 5S RNA and a 40-K protein which is required for 5S RNA transcription in vitro. Proteolytic digestion of the protein in the particle yields periodic intermediates spaced at 3-K intervals and a limit digest containing 3-K fragments. The native particle is shown to contain 7-11 zinc atoms. These data suggest that the protein contains repetitive zinc-binding domains. Analysis of the amino acid sequence reveals nine tandem similar units, each consisting of approximately 30 residues and containing two invariant pairs of cysteines and histidines, the most common ligands for zinc. The linear arrangement of these repeated, independently folding domains, each centred on a zinc ion, comprises the major part of the protein. Such a structure explains how this small protein can bind to the long internal control region of the 5S RNA gene, and stay bound during the passage of an RNA polymerase molecule.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [8] |
The three-dimensional solution structure of a zinc finger nucleic acid binding motif has been determined by nuclear magnetic resonance (NMR) spectroscopy. Spectra of a synthetic peptide corresponding to a single zinc finger from the Xenopus protein Xfin yielded distance and dihedral angle constraints that were used to generate structures from distance geometry and restrained molecular dynamics calculations. The zinc finger is an independently folded domain with a compact globular structure in which the zinc atom is bound by two cysteine and two histidine ligands. The polypeptide backbone fold consists of a well-defined helix, starting as alpha and ending as 3(10) helix, packed against two beta strands that are arranged in a hairpin structure. A high density of basic and polar amino acid side chains on the exposed face of the helix are probably involved in DNA binding.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [9] |
In this study, we describe the identification and partial characterization of 101 potential human zinc finger protein genes (ZnFPs). These sequences were isolated by hybridization of cosmids, obtained from mouse-human cell lines enriched for chromosome 11p, with an oligonucleotide specific for the "link" sequence between contiguous zinc fingers. Sixty-nine of these cosmids were regionally localized to human prometaphase chromosomes by in situ hybridization. The localization of these cosmids suggests that a number of finger protein genes occur in linked clusters. Their assignment to chromosomes 3p, 11p, 19p, 19qter, 20p, and 21q makes them valuable as markers or "candidate" genes for diseases associated with these chromosome regions.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [10] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [11] |
The expression of Tripartite motif-containing protein 28 (TRIM28)/Krüppel-associated box (KRAB)-associated protein 1 (KAP1), is elevated in at least 14 tumor types, including solid and hematopoietic tumors. High level of TRIM28 is associated with triple-negative subtype of breast cancer (TNBC), which shows higher aggressiveness and lower survival rates. Interestingly, TRIM28 is essential for maintaining the pluripotent phenotype in embryonic stem cells. Following on that finding, we evaluated the role of TRIM28 protein in the regulation of breast cancer stem cells (CSC) populations and tumorigenesis in vitro and in vivo. Downregulation of TRIM28 expression in xenografts led to deceased expression of pluripotency and mesenchymal markers, as well as inhibition of signaling pathways involved in the complex mechanism of CSC maintenance. Moreover, TRIM28 depletion reduced the ability of cancer cells to induce tumor growth when subcutaneously injected in limiting dilutions. Our data demonstrate that the downregulation of TRIM28 gene expression reduced the ability of CSCs to self-renew that resulted in significant reduction of tumor growth. Loss of function of TRIM28 leads to dysregulation of cell cycle, cellular response to stress, cancer cell metabolism, and inhibition of oxidative phosphorylation. All these mechanisms directly regulate maintenance of CSC population. Our original results revealed the role of the TRIM28 in regulating the CSC population in breast cancer. These findings may pave the way to novel and more effective therapies targeting cancer stem cells in breast tumors.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [12] |
Chronic lymphocytic leukaemia (CLL) is associated with apoptosis resistance and defective control of cell growth. Our study describes for the first time a critical role in CLL for the KRAB-zinc finger protein ZNF224. High ZNF224 transcript levels were detected in CLL patients with respect to control cells. Moreover, ZNF224 expression was significantly lowered after conventional chemotherapy treatment in a subset of CLL patients. By in vitro experiments we confirmed that ZNF224 expression is suppressed by fludarabine and demonstrated that ZNF224 is involved in apoptosis resistance in CLL cells. Moreover, we showed that ZNF224 positively modulates cyclin D3 gene expression. Consistently, we observed that alteration of ZNF224 expression leads to defects in cell cycle control. All together, our results strongly suggest that in CLL cells high expression level of ZNF224 can lead to inappropriate cell growth and apoptosis resistance, thus contributing to CLL progression. Targeting ZNF224 could thus improve CLL response to therapy.© The Author 2016. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [13] |
KRAB zinc-finger proteins (KRAB-ZFPs) constitute a large subfamily of ZFPs of the Krüppel C2H2 type. KRAB (Krüppel-associated box) is an evolutionarily conserved protein domain found N-terminally with respect to the finger repeats. We report here the characterization of a particular subgroup of highly related human KRAB-ZFPs. ZNF91 is one representative of this subgroup and contains 35 contiguous finger repeats at its C-terminus. Three mRNA isoforms with sequence identity to ZNF91 were isolated by the polymerase chain reaction. These encode proteins with a KRAB domain present, partially deleted or absent. Five genomic fragments were characterized, each encoding part of a gene: the ZNF91 gene or one of four distinct, related KRAB-ZFP genes. All exhibit a common exon/intron organization with the variant zinc finger repeats organized in a single exon and the KRAB domain encoded by two separate exons. This positioning of introns supports the hypothesis that the mRNA isoforms encoding polypeptides with variability in the KRAB domain could arise by alternative splicing. By in situ chromosomal mapping studies and by analysis of fragments from a human genomic yeast artificial chromosome library containing KRAB-ZFP genes, we show that these genes occur in clusters; in particular, a gene complex containing over 40 genes has been identified in chromosomal region 19p12-p13.1. These ZNF91-related genes probably arose late during evolution since no homologous genes are detected in the mouse and rat genomes. Although the transcription of members of this KRAB-ZFP gene subgroup is detectable in all human tissues, their expression is significantly higher in human T lymphoid cells.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [14] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [15] |
胡凯, 胡静, 孙子久, 等. UPF1在乳腺癌细胞中的表达与作用的研究. 中国生物工程杂志, 2022, 42(1-2): 58-71.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [16] |
The KRAB-ZNF (Krüppel-associated box domain zinc finger) gene family is composed of a large number of highly homologous genes, gene isoforms, and pseudogenes. The proteins encoded by these genes, whose expression is often tissue-specific, act as epigenetic suppressors contributing to the addition of repressive chromatin marks and DNA methylation. Due to its high complexity, the KRAB-ZNF family has not been studied in sufficient detail, and the involvement of its members in carcinogenesis remains mostly unexplored. In this study, we aimed to provide a comprehensive description of cancer-associated KRAB-ZNFs using publicly available The Cancer Genome Atlas pan-cancer datasets. We analyzed 6727 tumor and normal tissue samples from 16 cancer types. Here, we showed that a small but distinctive cluster of 16 KRAB-ZNFs is commonly upregulated across multiple cancer cohorts in comparison to normal samples. We confirmed these observations in the independent panels of lung and breast cancer cell lines and tissues. This upregulation was also observed for most of the KRAB-ZNF splicing variants, whose expression is simultaneously upregulated in tumors compared to normal tissues. Finally, by analyzing the clinicopathological data for breast and lung cancers, we demonstrated that the expression of cancer-associated KRAB-ZNFs correlates with patient survival, tumor histology, and molecular subtyping. Altogether, our study allowed the identification and characterization of KRAB-ZNF factors that may have an essential function in cancer biology and thus potential to become novel oncologic biomarkers and treatment targets.© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [17] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [18] |
Background: Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective.;Results: Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci.;Conclusions: The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [19] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [20] |
Cancer cells possess a broad spectrum of migration and invasion mechanisms. These include both individual and collective cell-migration strategies. Cancer therapeutics that are designed to target adhesion receptors or proteases have not proven to be effective in slowing tumour progression in clinical trials--this might be due to the fact that cancer cells can modify their migration mechanisms in response to different conditions. Learning more about the cellular and molecular basis of these different migration/invasion programmes will help us to understand how cancer cells disseminate and lead to new treatment strategies.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [21] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [22] |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| [23] |
欧阳琴, 李艳萌, 徐安健, 等. GTF2H2通过介导AKT信号通路影响肝癌细胞Hep3B的增殖和迁移. 中国生物工程杂志, 2021, 41(6): 4-12.
{{custom_citation.content}}
{{custom_citation.annotation}}
|
| {{custom_ref.label}} |
{{custom_citation.content}}
{{custom_citation.annotation}}
|
PDF(2746 KB)
图1 以1% O2浓度缺氧处理12 h、24 h后肝癌细胞中ZNF92的mRNA表达与蛋白质表达图2 敲低ZNF92后肝癌细胞ZEB1、SLUG的蛋白表达变化图3 敲低ZNF92对肝癌细胞迁移、侵袭和增殖能力的影响图4 ZNF92基因稳定敲低的肝癌细胞株中瞬时转染ZEB1 siRNA 后肝癌细胞迁移、侵袭能力的变化图5 ZNF92基因稳定敲低的肝癌细胞株中瞬时转染HIF-1α siRNA 后肝癌细胞迁移、侵袭能力的变化/
| 〈 |
|
〉 |
