scholarly journals Methionine Sulfoxide Reductase B1 Regulates Hepatocellular Carcinoma Cell Proliferation and Invasion via the Mitogen-Activated Protein Kinase Pathway and Epithelial-Mesenchymal Transition

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Qiang He ◽  
Hui Li ◽  
Fanzhi Meng ◽  
Xiangjun Sun ◽  
Xu Feng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Mapk Pathway ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Methionine sulfoxide reductase B1 (MsrB1) is a member of the selenoprotein family, which contributes to the reduction of methionine sulfoxides produced from reactive oxygen species (ROS) by redox processes in energy pathways. However, few studies have examined the role of MsrB1 in human hepatocellular carcinoma (HCC). We observed that MsrB1 is highly expressed in HCC tissues and that its expression correlated with the prognoses of patients with HCC after hepatectomy. In vitro, knockdown of MsrB1 inhibits HCC cell growth by MTT and EdU proliferation assay, and MsrB1 interference enhances H2O2/trx-induced apoptosis. We observed that phosphorylation of the key proteins of the MAPK pathway, namely, ERK, MEK, and p53, was inhibited, but PARP and caspase 3 were increased, thus infecting mitochondrial integrity. In vivo, MsrB1 knockdown effectively inhibited tumor growth. Furthermore, MsrB1 knockdown reduced HCC cell migration and invasion in a transwell assay through inhibition of cytoskeletal rearrangement and spread. This change was linked to epithelial-mesenchymal transition (EMT) inhibition resulting from increases in E-cadherin expression and decreases in expression in TGF-β1, Slug, MMP-2/9, and so on. MsrB1 regulates HCC cell proliferation and migration by modulating the MAPK pathway and EMT. Thus, MsrB1 may be a novel therapeutic target with respect to the treatment of HCC.

scholarly journals Upregulation of Long Non-Coding RNA PlncRNA-1 Promotes Metastasis and Induces Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma

2016 ◽  
Vol 38 (2) ◽  
pp. 836-846 ◽  
Author(s):  
Liyang Dong ◽  
Junwei Ni ◽  
Wenhao Hu ◽  
Chang Yu ◽  
Haiyan Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Clinicopathological Characteristics ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Promote Tumor Growth

Background/Aims: PlncRNA-1 has been demonstrated to promote malignancy in various cancers. The present study aims to investigate the expression pattern, prognosis value and the function of PlncRNA-1 in human hepatocellular carcinoma (HCC). Methods: The expression of PlncRNA-1 in 84 pairs of HCC and their matched normal tissues was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The correlations of PlncRNA-1 expression and clinicopathological characteristics and prognosis were also analyzed. The biological role of PlncRNA-1 in cell proliferation, migration and invasion was examined in vitro and in vivo. Results: The results showed that the level of PlncRNA-1 expression was significantly increased in HCC tissues and significantly correlated with tumor size, vascular invasion and advanced TNM stage. Moreover, patients with high levels of PlncRNA-1 expression had relatively poor prognostic outcomes, serving as an independent prognostic factor for HCC. In vitro functional assays indicated that knockdown of PlncRNA-1 expression significantly reduced cell proliferation, migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) signaling. Animal model experiments confirmed the ability of PlncRNA-1 to promote tumor growth in vivo. Conclusions: Taken together, our findings suggest that PlncRNA-1 may serve as an oncogene in HCC progression and represent a valuable prognostic marker and potential therapeutic target for HCC.

scholarly journals Scorpion inhibits epithelial–mesenchymal transition and metastasis of hepatocellular carcinoma

2018 ◽  
Vol 243 (7) ◽  
pp. 645-654 ◽  
Author(s):  
Yi-Quan Yan ◽  
Juan Xie ◽  
Jing-Fu Wang ◽  
Zhao-Feng Shi ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Unfavorable Clinical Outcome ◽  
Metastasis Models ◽  
Tumor Growth And Metastasis

Hepatocellular carcinoma (HCC) is one of the most malignant diseases worldwide. The unfavorable clinical outcome and poor prognosis are due to high rates of recurrence and metastasis after treatments. Some scholars of traditional Chinese medicine suggested that endogenous wind-evil had played an important role in metastasis of malignant tumor. Therefore, the drug of dispelling wind-evil could be used to prevent cancer metastasis and improve the poor prognosis. So we wondered whether Scorpion, one of the most important wind calming drugs, has antitumor effect especially in epithelial–mesenchymal transition (EMT) and metastasis of HCC in this research. We found that Scorpion-medicated serum could inhibit proliferation, induce apoptosis, and decrease migration and invasion capacity of Hepa1-6 cells in vitro. Meanwhile, we observed that water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT, which is characterized by increased epithelial marker E-cadherin expression and decreased mesenchymal markers N-cadherin and Snail expression following Scorpion treatment both in vitro and in vivo. These results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis. Impact statement The unfavorable clinical outcome and poor prognosis of hepatocellular carcinoma (HCC) are due to high rates of recurrence and metastasis after treatments. Here we found Scorpion, one of the most important wind calming drugs, has antitumor effect. Scorpion-medicated serum inhibited the proliferation, induced apoptosis, and decreased migration and invasion capacity of Hepa1-6 cells in vitro. Water decoction of Scorpion restrained tumor growth and metastasis in nude mouse of HCC metastasis models. Further experiments showed that Scorpion could suppress EMT of HCC both in vitro and in vivo. Our results suggested that the Scorpion could inhibit Hepa1-6 cells’ invasion and metastasis in part by reversing EMT and providing a possible potential approach for preventing HCC metastasis.

scholarly journals Chromatin remodeling factor ARID2 suppresses hepatocellular carcinoma metastasis via DNMT1-Snail axis

2020 ◽  
Vol 117 (9) ◽  
pp. 4770-4780 ◽  
Author(s):  
Hao Jiang ◽  
Hui-Jun Cao ◽  
Ning Ma ◽  
Wen-Dai Bao ◽  
Jing-Jing Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chromatin Remodeling ◽  
Epithelial Mesenchymal Transition ◽  
Positive Association ◽  
Mechanistic Study ◽  
Migration And Invasion ◽  
Metastasis Suppressor ◽  
Mesenchymal Transition ◽  
Hcc Cells

Recurrence and metastasis remain the major obstacles to successful treatment of hepatocellular carcinoma (HCC). Chromatin remodeling factor ARID2 is commonly mutated in HCC, indicating its important role in cancer development. However, its role in HCC metastasis is largely elusive. In this study, we find that ARID2 expression is significantly decreased in metastatic HCC tissues, showing negative correlation with pathological grade, organ metastasis and positive association with survival of HCC patients. ARID2 inhibits migration and invasion of HCC cells in vitro and metastasis in vivo. Moreover, ARID2 knockout promotes pulmonary metastasis in different HCC mouse models. Mechanistic study reveals that ARID2 represses epithelial–mesenchymal transition (EMT) of HCC cells by recruiting DNMT1 to Snail promoter, which increases promoter methylation and inhibits Snail transcription. In addition, we discover that ARID2 mutants with disrupted C2H2 domain lose the metastasis suppressor function, exhibiting a positive association with HCC metastasis and poor prognosis. In conclusion, our study reveals the metastasis suppressor role as well as the underlying mechanism of ARID2 in HCC and provides a potential therapeutic target for ARID2-deficient HCC.

scholarly journals lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting ZEB1

2018 ◽  
Vol 48 (5) ◽  
pp. 1928-1941 ◽  
Author(s):  
Chuan He ◽  
Zhigang Liu ◽  
Li Jin ◽  
Fang Zhang ◽  
Xinhao Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: MicroRNA-142-3p (miR-142-3p) is dysregulated in many malignancies and may function as a tumor suppressor or oncogene in tumorigenesis and tumor development. However, few studies have investigated the clinical significance and biological function of miR-142-3p in hepatocellular carcinoma (HCC). Methods: The expression levels of taurine upregulated gene 1 (TUG1), miR-142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC tissues and cell lines by quantitative real-time PCR. MTT and colony formation assays were used to detect cell proliferation ability, transwell assays were used to assess cell migration and invasion, and luciferase reporter assays were used to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p. Tumor formation was evaluated through in vivo experiments. Results: miR-142-3p was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell proliferation, cell migration, cell invasion, and the epithelial-mesenchymal transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT in nude mice. Conclusion: The results of this study suggest that the TUG1/miR-142-3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

scholarly journals Silencing of the TROP2 gene suppresses proliferation and invasion of hepatocellular carcinoma HepG2 cells

2019 ◽  
Vol 47 (3) ◽  
pp. 1319-1329 ◽  
Author(s):  
Jian Zhang ◽  
Hai Ma ◽  
Liu Yang ◽  
Hongchun Yang ◽  
Zhenxing He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Human Trophoblast ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Proliferation And Invasion

Objectives Overexpression of human trophoblast cell surface antigen 2 (Trop2) has been observed in many cancers; however, its roles in proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma (HCC) remain unclear. Thus, this study aimed to characterize the function of Trop2 in HCC. Methods Trop2 protein expression was detected by immunohistochemistry in HCC tissues. Cell proliferation, apoptosis, and invasion were respectively measured by CCK-8, flow cytometry, Transwell, and wound healing assays. Expression levels of epithelial–mesenchymal transition-related proteins and Trop2 protein in HCC cell lines were detected by western blotting after silencing of the TROP2 gene. Results Trop2 protein was highly expressed in HCC tissues and HCC cell lines. Trop2 mRNA and protein expression levels decreased in HepG2 and HCCLM3 cells after transfection with Trop2 siRNA. Silencing of the TROP2 gene in HepG2 and HCCLM3 cells strongly inhibited cell proliferation and migration, while enhancing cell apoptosis. Investigation of the molecular mechanism revealed that silencing of the TROP2 gene suppressed epithelial–mesenchymal transition of HepG2 and HCCLM3 cells. Conclusions The results of the present study may improve understanding of the role of Trop2 in regulation of cell proliferation and invasion, and may aid in development of novel therapy for HCC.

SOX10 induces epithelial–mesenchymal transition and contributes to nasopharyngeal carcinoma progression

2018 ◽  
Vol 96 (3) ◽  
pp. 326-331 ◽  
Author(s):  
Ping He ◽  
Xiaojie Jin
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Objective: The aim of this study was to investigate the role of SOX10 in nasopharyngeal carcinoma (NPC) and the underlying molecular mechanisms. Methods: The expression of SOX10 was initially assessed in human NPC tissues and a series of NPC cell lines through quantitative real-time PCR (qRT-PCR) and Western blot. Then, cell proliferation, cycle, migration, and the invasiveness of NPC cells with knockdown of SOX10 were examined by MTT, flow cytometry, and Transwell migration and invasion assays, respectively. Finally, nude mice tumorigenicity experiments were performed to evaluate the effects of SOX10 on NPC growth and metastasis in vivo. Results: SOX10 was significantly increased in NPC tissues and cell lines. In-vitro experiments revealed that loss of SOX10 obviously inhibited cell proliferation, migration, and invasiveness, as well as the epithelial–mesenchymal transition (EMT) process in NPC cells. In-vivo experiments further demonstrated that disrupted SOX10 expression restrained NPC growth and metastasis, especially in lung and liver. Conclusion: Taken together, our data confirmed the role of SOX10 as an oncogene in NPC progression, and revealed that SOX10 may serve as a novel biomarker for diagnosis of NPC, as well as a potential therapeutic target against this disease.

scholarly journals microRNA-16 via Twist1 inhibits EMT induced by PM2.5 exposure in human hepatocellular carcinoma

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 673-682 ◽  
Author(s):  
Hao Zhang ◽  
Zhihu Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Human Hepatocellular Carcinoma ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition

AbstractEpidemiological study has confirmed that PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 μm) is associated with the incidence and progression of human hepatocellular carcinoma (HCC). Accordingly, this study was undertaken to investigate the pro-metastatic effects of PM2.5 on human HCC cell line SMMC-7721 in vitro and to explore the underlying mechanisms. CCK-8 assay was performed to examine the effect of PM2.5 on the proliferation of SMMC-7721 cells; scratch wound assay and transwell matrigel system has been used to examine the effect of PM2.5 on the migration and invasion ability of SMMC-7721 cells; furthermore, effect of PM2.5 on epithelial mesenchymal transition (EMT) of SMMC-7721 cells were examined by examining the EMT markers vimentin, ɑ-smooth muscle actin (ɑ-SMA), and E-cadherin; furthermore, the roles of microRNA-16 (miR-16) and its target Twist1 in PM2.5 induced carcinogenic effects were also examined. Results of CCK-8 assay suggested that PM2.5 promoted the proliferation of SMMC-7721 cells in a dose and time dependent manner. PM2.5 also markedly promoted the migration and invasion ability of SMMC-7721 cells. Moreover, epithelial mesenchymal transition (EMT) was also triggered by PM2.5. On the other hand, microRNA-16 (miR-16) and its target Twist1 was found to be mediated by PM2.5, and miR-16 mimic could suppress the metastatic ability of SMMC-7721 cells exposure to PM2.5 via inversely regulating the expression of Twist1. Furthermore, dual Luciferase reporter assay confirmed the specifically binding of miR-16 to the predicted 3′-UTR of Twist1. The present study confirmed the pro-proliferative and pro-metastatic effect of PM2.5 on HCC cell line SMMC-7721. The possible mechanisms were EMT process induced by PM2.5 in SMMC-7721 cells, which was accompanied by a decrease in miR-16 and increase in Twist1 expression.

scholarly journals Knockdown of microRNA-214-3p Promotes Tumor Growth and Epithelial-Mesenchymal Transition in Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5875
Author(s):  
Patrice Cagle ◽  
Nikia Smith ◽  
Timothy O. Adekoya ◽  
Yahui Li ◽  
Susy Kim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Protein Tyrosine Kinase ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Oncogenic Signaling ◽  
Mesenchymal Transition

Abnormal expression of microRNA miR-214-3p (miR-214) is associated with multiple cancers. In this study, we assessed the effects of CRISPR/Cas9 mediated miR-214 depletion in prostate cancer (PCa) cells and the underlying mechanisms. Knockdown of miR-214 promoted PCa cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and increased resistance to anoikis, a key feature of PCa cells that undergo metastasis. The reintroduction of miR-214 in miR-214 knockdown cells reversed these effects and significantly suppressed cell proliferation, migration, and invasion. These in vitro studies are consistent with the role of miR-214 as a tumor suppressor. Moreover, miR-214 knockout increased tumor growth in PCa xenografts in nude mice supporting its anti-oncogenic role in PCa. Knockdown of miR-214 increased the expression of its target protein, Protein Tyrosine Kinase 6 (PTK6), a kinase shown to promote oncogenic signaling and tumorigenesis in PCa. In addition, miR-214 modulated EMT as exhibited by differential regulation of E-Cadherin, N-Cadherin, and Vimentin both in vitro and in vivo. RNA-seq analysis of miR-214 knockdown cells revealed altered gene expression related to PCa tumor growth pathways, including EMT and metastasis. Collectively, our findings reveal that miR-214 is a key regulator of PCa oncogenesis and is a potential novel therapeutic target for the treatment of the disease.

scholarly journals Mechanism and Molecular Network of RBM8A-Mediated Regulation of Oxaliplatin Resistance in Hepatocellular Carcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Rong Liang ◽  
Jinyan Zhang ◽  
Zhihui Liu ◽  
Ziyu Liu ◽  
Qian Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Binding Motif ◽  
Mesenchymal Transition ◽  
Regulatory Pathways ◽  
Wide Range

RNA-binding motif protein 8A (RBM8A) is abnormally overexpressed in hepatocellular carcinoma (HCC) and involved in the epithelial-mesenchymal transition (EMT). The EMT plays an important role in the development of drug resistance, suggesting that RBM8A may be involved in the regulation of oxaliplatin (OXA) resistance in HCC. Here we examined the potential involvement of RBM8A and its downstream pathways in OXA resistance using in vitro and in vivo models. RBM8A overexpression induced the EMT in OXA-resistant HCC cells, altering cell proliferation, apoptosis, migration, and invasion. Moreover, whole-genome microarrays combined with bioinformatics analysis revealed that RBM8A has a wide range of transcriptional regulatory capabilities in OXA-resistant HCC, including the ability to regulate several important tumor-related signaling pathways. In particular, histone deacetylase 9 (HDAC9) emerged as an important mediator of RBM8A activity related to OXA resistance. These data suggest that RBM8A and its related regulatory pathways represent potential markers of OXA resistance and therapeutic targets in HCC.

scholarly journals Reexpression of Let-7g MicroRNA Inhibits the Proliferation and Migration via K-Ras/HMGA2/Snail Axis in Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Ke-ji Chen ◽  
Ying Hou ◽  
Kui Wang ◽  
Jun Li ◽  
Yong Xia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Mtt Method ◽  
Carcinoma Cell Lines ◽  
And Migration

Let-7 family microRNAs have been reported to be downregulated in human hepatocellular carcinoma in comparison with normal hepatic tissues. Among them, let-7g was identified as the lowest expression using real-time RT-PCR. However, the mechanism by which let-7g works in hepatocellular carcinoma remains unknown. Here, in our present study, we have had let-7g reexpressedin vitroin hepatocellular carcinoma cell lines MHCC97-H and HCCLM3 via transfection. The proliferation after reexpression of let-7g was assayed using MTT method; the migration and invasion after restoration were detected by wound-healing and Transwell assay, respectively. We found using Western-blotting that let-7g can regulate epithelial-mesenchymal transition (EMT) by downregulating K-Ras and HMGA2A after reexpresssion. Xenografted nude mice were used to observe whether or not reexpression of let-7g could have potential therapeutic ability.In vivo, to observe the association with let-7g expression and overall prognosis, 40 paired cases of hepatocellular carcinoma were analyzed using in situ hybridization (ISH). It was found that reexpression of let-7g can inhibit the proliferation, migration, and invasion significantly, and that low expression of let-7g was significantly associated with poorer overall survival. Taken together, let-7g could be used as a promising therapeutic agentin vivoin the treatment of hepatocellular carcinoma at the earlier stage.

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