scholarly journals Overexpression of Uric Acid Transporter SLC2A9 Inhibits Proliferation of Hepatocellular Carcinoma Cells

2019 ◽  
Vol 27 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Xiaoying Han ◽  
Jing Yang ◽  
Dong Li ◽  
Zewei Guo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Uric Acid ◽  
Tumor Suppressor ◽  
Cell Apoptosis ◽  
Suppressor Gene ◽  
Potential Contribution ◽  
Acid Transporter ◽  
Underlying Mechanisms ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. Although the mechanisms of HCC progression are not well understood, recent studies demonstrated the potential contribution of uric acid transporter SLC2A9 to tumor suppression. However, the roles and underlying mechanisms are still unknown. We aimed to study the roles and mechanisms of SLC2A9 in HCC. The present study showed that SLC2A9 expression was decreased in human HCC tissues and cell lines. In addition, overexpression of SLC2A9 inhibited HCC cell proliferation. SCL2A9 induced HCC cell apoptosis by inhibiting the expression of caspase 3. Our study also revealed that upregulation of SLC2A9 reduced intracellular reactive oxygen species (ROS) accumulation. Furthermore, SLC2A9 increased the mRNA and protein expression of tumor suppressor p53 in HCC cells. Probenecid inhibits SLC2A9-mediated uric acid transport, which promotes cell proliferation, inhibits cell apoptosis, induces intracellular ROS, and decreases the expression of p53 in HCC cells. Therefore, the present study demonstrated that SLC2A9 may be a novel tumor suppressor gene and a potential therapeutic target in HCC.

Chondroitin polymerizing factor (CHPF) contributes to malignant proliferation and migration of hepatocellular carcinoma cells

2020 ◽  
Vol 98 (3) ◽  
pp. 362-369
Author(s):  
Qigang Xu ◽  
Wei Lin ◽  
Chonglin Tao ◽  
Xiaming Huang ◽  
Junjian Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Colony Formation ◽  
Malignant Tumors ◽  
Mrna And Protein Expression ◽  
Advanced Stages ◽  
Human Digestive System ◽  
And Migration ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the human digestive system, and has been recognized as a serious threat to public health worldwide. This study explored the role of chondroitin polymerizing factor (CHPF) in the development and metastasis of HCC. Immunohistochemistry analysis was performed to detect CHPF expression in HCC tissues and para-carcinoma tissues. qRT-PCR and Western blot analysis were used to determine the mRNA and protein expression of CHPF. MTT assays, colony formation assays, and flow cytometry were used to evaluate the cell proliferation, colony formation, and cell apoptosis, respectively. Wound-healing and Transwell assays were performed to evaluate cell migration. The results show that CHPF was not only up-regulated in HCC tissues compared with para-carcinoma tissues, but was also related with more advanced stages of HCC. Further studies revealed that CHPF knockdown significantly inhibited cell proliferation and colony formation, and induce cell apoptosis of HCC cells. Moreover, suppressing the expression of CHPF reduced the migration and invasiveness of HCC cells. In conclusion, we demonstrated that CHPF plays important roles in the development and progression of HCC, and high expression levels of HCC may be related with poorer prognosis. The results from this study may provide a potential therapeutic target for HCC treatment.

Silencing non-SMC chromosome-associated polypeptide G inhibits proliferation and induces apoptosis in hepatocellular carcinoma cells

2018 ◽  
Vol 96 (12) ◽  
pp. 1246-1254 ◽  
Author(s):  
Kaikun Liu ◽  
Yumin Li ◽  
Bo Yu ◽  
Furong Wang ◽  
Taiyu Mi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Mrna Level ◽  
A Subunit ◽  
Underlying Mechanisms ◽  
Colony Forming Capacity ◽  
Hcc Cells

The present study was designed to investigate the significance of non–structural maintenance of chromosomes (non-SMC) chromosome-associated polypeptide G (NCAPG), a subunit of condensin complex I, in the development of hepatocellular carcinoma (HCC). NCAPG protein expression in human HCC and paracancerous hepatic tissues were examined using immunohistochemistry, and NCAPG mRNA expression in HCC cell lines were quantified using quantitative RT–PCR. Lentivirus-mediated RNA interference was used to silence NCAPG in HCC cells. Cell proliferation was monitored by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Apoptosis was determined by flow cytometry. The results showed that increased protein expression of NCAPG was found in HCC tissues compared with the matched paracancerous hepatic tissues. At the mRNA level, increased expression of NCAPG was found in HCC cells as opposed to the normal hepatocytes. Silencing of NCAPG in BEL-7404 and SMMC-7721 cells led to decreased cell proliferation and increased apoptosis. These changes were associated with increased mRNA expressions of P53, P27, and Bad, but decreased mRNA expression of EGFR, Akt, survivin, and JNK. NCAPG might play an oncogenic role in the development of liver cancer. Further studies to clarify its role and underlying mechanisms in the development of liver cancer are warranted.

scholarly journals MicroRNA-2392 Functions as a Tumor Suppressor Gene and Inhibits Malignant Progression of Hepatocellular Carcinoma via Directly Targeting JAG2

2021 ◽  
Author(s):  
Chunying Liu ◽  
Bin Sun ◽  
Weidan Ji ◽  
Xuejing Lin ◽  
Lei Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Malignant Progression ◽  
Spheroid Formation ◽  
Down Regulation ◽  
Potential Target ◽  
Target Mrnas ◽  
Hcc Cells

Abstract Background Dysregulation of microRNA (miRNA) expression in various cancers and their vital roles in malignant progression of cancers are well investigated. Our previous studies have analyzed miRNAs that promote malignant progression of hepatocellular carcinoma (HCC), this study aim to systematically elucidate metastasis suppressor miRNAs in HCC. Methods High-throughput RNA sequencing analysis was used to identify anti-metastatic miRNAs of HCC. The relative expression levels of miRNAs were confirmed by qRT-PCR. The biological functions of miRNAs were studied by CCK8, wound-healing, transwell, colony formation in HCC cells. Circulating tumor cells were enriched from blood samples of HCC patients and cultured by three-dimensional (3D) system. The potential target mRNAs of miRNAs were analyzed by bioinformatics analysis and confirmed by luciferase reporter assay. Liver metastasis model via tail vein injection was further examined in nude mice. Kaplan-Meier and Cox regression were used to analyze the value of potential target mRNAs on overall survival. Results miR-2392 was significantly down-regulated in HCC. Overexpression of miR-2392 suppressed proliferation, mobility, spheroid formation and maintenance of cancer stem cells (CSC)-like characteristics in HCC cell lines, whereas down-regulation of miR-2392 led to the opposite results. CTCs from HCC patients with lower serum miR-2392 level had stronger cell spheroid formation ability. A negative correlation between the content of miR-2392 in serum and the number of CTC spheroids had been found. We identified Jagged2 (JAG2) as a direct target of miR-2392, miR-2392 inhibited the expression and nuclear accumulation of JAG2 by targeting 3’-UTR of JAG2. HCC cells were treated with LV-miR-2392 inhibitor and JAG2-siRNA to explore the mechanism of miR-2392 and JAG2 on HCC. Down-regulation of JAG2 inhibited the overexpression effects of miR-2392 in vitro and in vivo. JAG2 is highly expressed in HCC and is closely related to poor prognosis and survival of patients. Conclusions Our findings indicated a significant role of the miR-2392/JAG2 axis in suppressing HCC cell growth and aggressiveness, miR-2392 may play a role as a tumor suppressor gene to guide the individualized precise treatment of HCC.

MiR-3144 Suppresses Cell Proliferation, Migration, Invasion and Promotes Cell Apoptosis by Targeting Steap4 in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (8) ◽  
pp. 1100-1107
Author(s):  
Qiuyuan Shi ◽  
Dandan Shen ◽  
Yuanjiang Shang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Apoptotic Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Novel Target ◽  
Hcc Cells

Background: MicroRNAs (miRNAs) play important roles in the carcinogenesis and progression of hepatocellular carcinoma (HCC). Previous studies have shown that miR-3144 is down-regulated in HCC tissues. The present study investigated the expression and biological roles, underlying mechanisms of miR-3144 in HCC cell lines. Methods and material: RT-qPCR analysis was performed to detect miR-3144 expression in the HCC cell lines and normal hepatic cell line. CCK-8 assay showed that the effect of miR-3144 expression on cell proliferation. Using wound healing assay and Transwell assay to detect the effect of miR-3144 on cell invasion and migration of HCC. Flow cytometry assay showed that miR-3144 induced apoptotic cell death in the SK-HEP-1 cells. Luciferase reporter assay was performed to evaluate the interaction between miR-3144 and the Steap4 3′-UTR. Western blotting assay were performed to investigate the effect of miR-3144 expression on the expression of CDK2, cyclinE1, p21, MMP2, MMP9 and Steap4. Results: MiR-3144 expression was downregulated in HCC cell lines. MiR-3144 overexpression inhibited the proliferation of HCC cells via regulating CDK2, cyclinE1 and p21 in SK-HEP-1 cells. MiR-3144 suppressed the migration and invasion of HCC cells via decreasing the MMP2 and MMP9. Further, miR-3144 promotes cell apoptosis of HCC. Moreover, miR-3144 negatively regulated Steap4 expression by directly binding to the 3′-UTR of Steap4 mRNA. Conclusion: Our results suggested that miR-3144 may be a novel target for future HCC therapy.

MiRNA-485-5p inhibited the proliferation and promoted the apoptosis of hepatocellular carcinoma cells by targeting MUC1

2020 ◽  
Author(s):  
Ming Li ◽  
Dong Zhu ◽  
Xiaozhen Peng ◽  
Pinyue Liu ◽  
Fen Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Western Blot ◽  
Binding Site ◽  
Cell Apoptosis ◽  
Carcinoma Cells ◽  
Luciferase Assay ◽  
Adjacent Tissue ◽  
Dual Luciferase Assay ◽  
Hcc Cells

Abstract Background The downregulation of miRNA-485-5-p was related to prognosis of various cancers, including hepatocellular carcinoma (HCC), while MUC1 was aberrantly expressed in many cancers and could be a biomarker for prognosis and diagnosis of cancers. The aim of the study was to investigate whether the miRNA-485-5p inhibited proliferation and promoted apoptosis by targeting MUC1 in HCC cells.Methods The expression of miRNA-485-5p in patients with HCC was measured by qPCR, and the epxression of MUC1 was detected by qPCR, western blot and immunohistochemistry. Bioinformatics and dual luciferase assay verified the targeting relationship between miRNA-485-5p and MUC1 in HCC cells. Cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by flow cytometry.Results The expression of miRNA-485-5p in HCC tissues is downregulated than that in adjacent tissue. However, the exprssion of MUC1 is opposite to the expression of miRNA-485-5p in the patients with HCC. Silencing MUC1 and overexpression miRNA-485-5p both inhibit proliferation and promote apoptosis in HCC cells. MiRNA-485-5p directly targete to the binding site of the MUC1 3’UTR and downregulated the expression of MUC1. Overexpression of MUC1 and miRNA-485-5p reverse the effect of miRNA-485-5p on the cell proliferation and apoptosis.Conclusion MiRNA-485-5p inhibits the proliferation and facilitates the apoptosis by negatively regulating the expression of MUC1 in HCC cells.

scholarly journals Depletion ofDNMT3ASuppressed Cell Proliferation and RestoredPTENin Hepatocellular Carcinoma Cell

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Zhujiang Zhao ◽  
Qingxiang Wu ◽  
Jian Cheng ◽  
Xuemei Qiu ◽  
Jianqiong Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Cpg Island ◽  
Cpg Islands ◽  
Promoter Hypermethylation ◽  
Suppressor Gene ◽  
Dna Methyltransferases ◽  
Cpg Island Methylation

Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed thatDNMT1andDNMT3Bplay an important role in CpG island methylation in tumorigenesis. Little is known about the role ofDNMT3Ain this process, especially in hepatocellular carcinoma (HCC). In the present study, increasedDNMT3Aexpression in 3 out of 6 HCC cell lines and 16/25 (64%) HCC tissues implied thatDNMT3Ais involved in hepatocellular carcinogenesis. Depletion ofDNMT3Ain HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%). Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153) of them contain CpG islands in their5′region. 13 of them includingPTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation ofPTENpromoter was observed inDNMT3A-depleted cells implying that DNMT3A silencedPTENvia DNA methylation. These results provide insights into the mechanisms ofDNMT3Ato regulate TSGs by an epigenetic approach in HCC.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Casein Kinase 1 ◽  
Mouse Xenograft Model ◽  
Hcc Cells

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.

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