EMT Of Hepatocellular Carcinoma Cells Research Articles

MiR-429 regulates the metastasis and EMT of HCC cells through targeting RAB23

Accumulating documents have revealed that microRNAs (miRNAs) play critical roles in the development and progression of tumors. MiR-429 has been reported to be involved in regulating various cellular processes. However, its biological role and underlying mechanism in hepatocellular carcinoma (HCC) still need to be further studied. The present study aimed to investigate the function of miR-429 in the progression of HCC. In terms of this paper, it was found that miR-429 was down-regulated in HCC tissues and cells. After being transfected with miR-429 mimics, miR-429 decreased the migratory capacity and reversed the EMT to MET in HCC cells. RAB23 was confirmed as a target of miR-429. Rescue assays further verified that the function of miR-429 in HCC cells was exerted through targeting RAB23. In general, it was concluded that the signal pathway miR-429/RAB23 might be a potential target for HCC treatment.

LncRNA GHET1 activated by H3K27 acetylation promotes cell tumorigenesis through regulating ATF1 in hepatocellular carcinoma

BackgroundGHET1 is one of tumor-related lncRNAs. We aimed to explore the functional involvement of GHET1 in hepatocellular carcinoma (HCC). MethodsIn this study, HCC tissues and the paired normal tissues were collected for the detection of target molecules. The expression level of target molecules in HCC tissues or cell lines was determined by qRT-PCR and western blot, respectively. The expression of endogenous GHET1 and ATF1 was modulated by using cell transfection. RNA pull down assay was performed to examine the interaction between GHET1 and ATF1. ChIP assay was conducted to determine the H3K27Ac acetylation of GHET1 promoter. ResultsH3K27 acetylation activated-GHET1 was upregulated in HCC tissues and cell lines. Moreover, GHET1 silencing could inhibit the proliferation, migration, invasion and EMT of HCC cells in vitro. GHET1 could regulate the expression of ATF1 mRNA and protein; RNA pull-down assays supported that GHET1 could bind to ATF1 protein. Furthermore, overexpression of ATF1 almost completely reversed the GHET1 knockdown mediated inhibition on the proliferation, migration, invasion and EMT of HCC cells. ConclusionLncRNA GHET1 was intimately involved in the occurrence and development of HCC through regulating ATF1.

CAPZA1 modulates EMT by regulating actin cytoskeleton remodelling in hepatocellular carcinoma

BackgroundEpithelial-mesenchymal transition (EMT) elicits dramatic changes, including cytoskeleton remodelling as well as changes in gene expression and cellular phenotypes. During this process, actin filament assembly plays an important role in maintaining the morphology and movement of tumour cells. Capping protein, a protein complex referred to as CapZ, is an actin-binding complex that can regulate actin cytoskeleton remodelling. CAPZA1 is the α1 subunit of this complex, and we hypothesized that CAPZA1 regulates EMT through the regulation of actin filaments assembly, thus reducing the metastatic ability of hepatocellular carcinoma (HCC) cells.MethodsImmunohistochemistry was used to detect CAPZA1 expression in 129 HCC tissues. Western blotting and qPCR were used to detect CAPZA1, EMT markers and EMT transcription factors in HCC cells. Transwell migration and invasion assays were performed to observe the migration and invasion of HCC cells. Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of HCC cells. Immunoprecipitation was used to detect the interaction between CAPZA1 and actin filaments. Finally, a small animal magnetic resonance imager (MRI) was used to observe metastases in HCC cell xenografts in the liver.ResultsCAPZA1 expression levels were negatively correlated with the biological characteristics of primary HCC and patient prognosis. CAPZA1 expression was negatively correlated with the migration and invasion of HCC cells. CAPZA1 down regulation promoted the migration and invasion of HCC cells. Conversely, CAPZA1 overexpression significantly inhibited the migration and invasion of HCC cells. Moreover, CAPZA1 expression levels were correlated with the expression of the EMT markers E-cadherin, N-cadherin and Vimentin. Furthermore, the expression of Snail1 and ZEB1 were negatively correlated with CAPZA1 expression levels. Similarly, CAPZA1 significantly inhibited intrahepatic metastases of HCC cells in an orthotopic transplantation tumour model.ConclusionsCAPZA1 inhibits EMT in HCC cells by regulating actin cytoskeleton remodelling, thereby reducing the metastatic ability of the cells. Together, our data suggest that CAPZA1 could be a useful biomarker for clinical determination of the prognosis of HCC patients.

Overexpression of OCT4 contributes to progression of hepatocellular carcinoma.

The abnormal change of octamer transcription factor 4 (OCT4) is associated with tumor progression; however, its effect on hepatocellular carcinoma (HCC) behavior remains unclear. The purpose of this study was to determine the correlation between HCC and OCT4. In the present study, IHC, western blot analysis, and QRT-PCR were performed to identify differentially expressed OCT4 in a series of HCC tissues and adjacent non-cancerous tissues. In addition, the functions of OCT4 on HCC progression were studied in vitro. Silencing of OCT4 with siRNA was performed in HCC cell lines, and the impact on proliferation, migration, and the EMT marker of HCC was analyzed. Our results found that OCT4 levels were significantly higher in HCC tissues compared with the adjacent non-cancerous tissues. Furthermore, OCT4 siRNA significantly reduced the proliferation rate of SMMC-7721 and HepG2 cells, inhibited the migration and inversion, and could reverse EMT in HCC cells, indicating that OCT4 plays a critical role in HCC progression. Our data suggest that the pathogenesis of human HCC may be mediated by OCT4, and thus, OCT4 could represent selective targets for the molecularly targeted treatments of HCC.

Over-expression of TRIM37 promotes cell migration and metastasis in hepatocellular carcinoma by activating Wnt/β-catenin signaling

Hepatocellular carcinoma (HCC) is the most common cancer in the world especially in East Asia and Africa. Advanced stage, metastasis and frequent relapse are responsible for the poor prognosis of HCC. However, the precise mechanisms underlying HCC remained unclear. So it is urgent to identify the pathological processes and relevant molecules of HCC. TRIM37 is an E3 ligase and has been observed deregulated expression in various tumors. Recent studies of TRIM37 have implicated that TRIM37 played critical roles in cell proliferation and other processes. In the present study, we demonstrated that TRIM37 expression was notably up-regulated in HCC samples and was associated with advanced stage and tumor volume, which all indicating the poor outcomes. We also found that TRIM37 could serve as an independent prognostic factor of HCC. During the course of in vitro and in vivo work, we showed that TRIM37 promoted HCC cells migration and metastasis by inducing EMT. Furthermore, we revealed that the effect of TRIM37 mediated EMT in HCC cells was achieved by the activation of Wnt/β-catenin signaling. These finding may provide insight into the understanding of TRIM37 as a novel critical factor of HCC and a candidate target for HCC treatment.

BMP‐9 induces EMT in hepatocellular carcinoma cells. Immunofluorescent staining against BMP‐9 (green) and E‐cadherin (red) of a hepatocellular carcinoma section from TNFα/cmyc bitransgenic mouse

Cancer ScienceVolume 104, Issue 3 p. March cover-March cover Cover ImageOpen Access BMP-9 induces EMT in hepatocellular carcinoma cells. Immunofluorescent staining against BMP-9 (green) and E-cadherin (red) of a hepatocellular carcinoma section from TNFα/cmyc bitransgenic mouse Qi Li, Search for more papers by this authorXing Gu, Search for more papers by this authorHonglei Weng, Search for more papers by this authorShahrouz Ghafoory, Search for more papers by this authorYan Liu, Search for more papers by this authorTeng Feng, Search for more papers by this authorJohanna Dzieran, Search for more papers by this authorLi Li, Search for more papers by this authorIryna Ilkavets, Search for more papers by this authorMarianna Kruithof- de Julio, Search for more papers by this authorStefan Munker, Search for more papers by this authorAlexander Marx, Search for more papers by this authorAlbrecht Piiper, Search for more papers by this authorEduardo Augusto Alonso, Search for more papers by this authorNorbert Gretz, Search for more papers by this authorChunfang Gao, Search for more papers by this authorStefan Wölfl, Search for more papers by this authorSteven Dooley, Search for more papers by this authorKatja Breitkopf-Heinlein, Search for more papers by this author Qi Li, Search for more papers by this authorXing Gu, Search for more papers by this authorHonglei Weng, Search for more papers by this authorShahrouz Ghafoory, Search for more papers by this authorYan Liu, Search for more papers by this authorTeng Feng, Search for more papers by this authorJohanna Dzieran, Search for more papers by this authorLi Li, Search for more papers by this authorIryna Ilkavets, Search for more papers by this authorMarianna Kruithof- de Julio, Search for more papers by this authorStefan Munker, Search for more papers by this authorAlexander Marx, Search for more papers by this authorAlbrecht Piiper, Search for more papers by this authorEduardo Augusto Alonso, Search for more papers by this authorNorbert Gretz, Search for more papers by this authorChunfang Gao, Search for more papers by this authorStefan Wölfl, Search for more papers by this authorSteven Dooley, Search for more papers by this authorKatja Breitkopf-Heinlein, Search for more papers by this author First published: 01 March 2013 https://doi.org/10.1111/cas.12090AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume104, Issue3March 2013Pages March cover-March cover RelatedInformation