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

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LncRNA HULC regulates hepatocellular carcinoma cell proliferation, apoptosis and epithelial-mesenchymal transition via the miR-372/CXCR4 axis

10.21203/rs.3.rs-18078/v1 ◽

2020 ◽

Author(s):

Hao Liu ◽

Xiaoli Zhou ◽

Jiayao Yang ◽

Zhaohong Shi

Keyword(s):

Public Health ◽

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Liver Cancer ◽

Protein Expression ◽

Epithelial Mesenchymal Transition ◽

Health Concern ◽

Mesenchymal Transition ◽

Cxcr4 Axis ◽

Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is a lethal malignancy and a major public health concern worldwide. Considering the public health risk posed by HCC, it is necessary to elucidate the mechanisms underlying liver cancer progression in order to identify more therapeutic targets. In this study, we will elucidate the role of LncRNA HULC in regulating HCC cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) via the miR-372/CXCR4 axis. Material and MethodsTarget genes were predicted using the online TargetScan database. Cell models of gene over-expression and silencing were established by transfection, and the mRNA and protein expression levels were measured by qRT-PCR and Western blotting, respectively. Cell viability, proliferation and apoptosis were measured by the CCK-8 assay, colony formation assay and Annexin V-FITC/PI staining, respectively. In situ protein expression in tissues was examined by immunohistochemical staining. Results HULC and CXCR4 were upregulated and miR-372 was downregulated in HCC tissue and cells. TargetScan prediction and dual luciferase assay revealed that miR-372 can target HULC or CXCR4. Furthermore, HULC and CXCR4 enhanced the viability of HCC cells, whereas miR-372 had the opposite effect. Consistent with this, HULC and CXCR4 increased the proliferation of these cells and miR-372 showed an inhibitory effect. Furthermore, HULC and CXCR4 blocked apoptosis in liver cancer cells and miR-372 facilitated the same. Finally, HULC and CXCR4 promoted EMT, as indicated by E-cadherin downregulation and Vimentin upregulation, whereas miR-372 had the opposite effects. Conclusion HULC upregulates CXCR4 in HCC cells by inhibiting miR-372, which in turn promotes the proliferation, inhibits the apoptosis and accelerates the EMT of HCC cells.

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

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15199489058224 ◽

2019 ◽

Vol 27 (5) ◽

pp. 533-540 ◽

Cited By ~ 1

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.

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Serum from Chronic Hepatitis B Patients Promotes Growth and Proliferation via the IGF-II/IGF-IR/MEK/ERK Signaling Pathway in Hepatocellular Carcinoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000489744 ◽

2018 ◽

Vol 47 (1) ◽

pp. 39-53 ◽

Cited By ~ 5

Author(s):

Yuanyuan Ji ◽

Zhidong Wang ◽

Haiyan Chen ◽

Lei Zhang ◽

Fei Zhuo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Chronic Hepatitis ◽

Cell Growth ◽

Hepatitis B ◽

Protein Expression ◽

Molecular Mechanisms ◽

Erk Signaling ◽

Mrna And Protein Expression ◽

Hcc Cells

Background/Aims: Chronic hepatitis B virus (HBV) infection (CHB) plays a central role in the etiology of hepatocellular carcinoma (HCC). Emerging evidence implicates insulin-like growth factor (IGF)-II as a major risk factor for the growth and development of HCC. However, the relationship between HBV infection and IGF-II functions remains to be elucidated. Methods: Levels of circulating IGF-II and IGF-I receptor (IGF-IR) in healthy donors (HDs) and CHB patients were tested by ELISA. Human HCC cell lines (HepG-2, SMMC-7721, MHCC97-H) were incubated with serum from HDs and CHB patients at various concentrations for 24, 48, and 72 h. MTT and plate colony formation assays, BrdU ELISA, ELISA, small-interfering RNA (siRNA) transfection, quantitative real-time PCR, and western blot were applied to assess the functional and molecular mechanisms in HCC cell lines. Results: Serum levels of IGF-II and IGF-IR were significantly higher in CHB patients than in HDs. Additionally, serum from CHB patients directly induced cell growth, proliferation, IGF-II secretion, and HDGF-related protein-2 (HRP-2) and nuclear protein 1 (NUPR1) mRNA and protein expression in HCC cells. Moreover, serum from CHB patients increased IGF-II–induced cell growth, proliferation, and HRP-2 and NUPR1 mRNA and protein expression in HCC cells. Blockade of IGF-IR clearly inhibited the above effects. Most importantly, interference with IGF-II function markedly repressed the cell proliferation and HRP-2 and NUPR1 mRNA and protein expression induced by serum from CHB patients. Furthermore, serum from CHB patients induced ERK phosphorylation via IGF-IR, with the MEK inhibitor PD98059 significantly decreasing CHB patient serum-induced IGF-II secretion, cell proliferation, and HRP-2 and NUPR1 mRNA and protein expression. Conclusion: Serum from CHB patients increases cell growth and proliferation and enhances HRP-2 and NUPR1 expression in HCC cells via the IGF-II/IGF-IR/MEK/ERK signaling pathway. These findings help to explain the molecular mechanisms underlying HBV-related HCC and may lead to the development of effective therapies.

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Long non-coding RNA RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis

Bioscience Reports ◽

10.1042/bsr20200297 ◽

2020 ◽

Vol 40 (3) ◽

Cited By ~ 1

Author(s):

Qin-Liang Fang ◽

Jian-Yin Zhou ◽

Yu Xiong ◽

Cheng-Rong Xie ◽

Fu-Qiang Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Protein Synthesis ◽

Protein Expression ◽

Mrna Expression ◽

Translation Initiation Factor ◽

Expression Level ◽

Mrna Expression Level ◽

Protein Expression Level ◽

Proliferation And Invasion

Abstract A newly identified lncRNA designated as RP11-284P20.2 has been identified to be up-regulated in hepatocellular carcinoma (HCC), but its role in HCC remain poorly understood. Quantitative PCR and immunocytochemical analysis were performed using the HCC tissues to identify the potential interaction partners of RP11-284P20.2. Moreover, RP11-284P20.2 was knocked down in HCC cell lines, HepG2 and SMMC7721, to investigate the influence of this lncRNA on cell growth properties. Additionally, RNA fluorescence in situ hybridization and immunofluorescence, RNA immunoprecipitation, and RNA pull-down assays were performed to determine the interaction of RP11-284P20.2 with c-met mRNA and eukaryotic translation initiation factor 3b (EIF3b). Silencing RP11-284P20.2 inhibited cell viability, migration, invasion, and colony formation, and increased apoptosis. Overexpression of c-met abolished these effects of RP11-284P20.2 in HCC cells. Histopathological examination showed that HCC tissues with high RP11-284P20.2 expression had higher c-met protein level than that in HCC tissues with low RP11-284P20.2 expression. However, there was no positive correlation between the expression levels of RP11-284P20.2 and c-met mRNA. RP11-284P20.2 knockdown led to a decease in c-met protein expression level, but did not affect the c-met mRNA expression level. These data suggest that RP11-284P20.2 regulates c-met protein expression level, which is independent of c-Met mRNA expression level. It was also confirmed that RP11-284P20.2 has high affinity toward both c-met mRNA and EIF3b protein, and hence RP11-284P20.2 probably recruits EIF3b protein to c-met mRNA and further facilitates its translation. RP11-284P20.2 promotes cell proliferation and invasion in hepatocellular carcinoma by recruiting EIF3b to induce c-met protein synthesis.

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Restoration of Epigenetically Silenced Sulfatase 1 Expression by 5-Aza-2′-Deoxycytidine Sensitizes Hepatocellular Carcinoma Cells to Chemotherapy-Induced Apoptosis

Medical Epigenetics ◽

10.1159/000375461 ◽

2015 ◽

Vol 3 (1) ◽

pp. 1-18 ◽

Cited By ~ 4

Author(s):

Abdirashid Shire ◽

Gwen Lomberk ◽

Jin-Ping Lai ◽

Hongzhi Zou ◽

Norihiko Tsuchiya ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Methylation ◽

Protein Expression ◽

Mrna Expression ◽

Cell Lines ◽

Gene Copy ◽

Drug Induced ◽

Sulfatase Activity ◽

Induced Apoptosis ◽

Hcc Cells

Background: Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer death worldwide. Sulfatase 1 (SULF1) functions as a tumor suppressor in HCC cell lines in vitro but also has an oncogenic effect in some HCCs in vivo. Aim: The purpose of this study was to examine the mechanisms regulating SULF1 and its function in HCC. Methods: First, SULF1 mRNA and protein expression were examined. Second, we examined SULF1 gene copy numbers in HCC cells. Third, we assessed whether DNA methylation or methylation and/or acetylation of histone marks on the promoter regulate SULF1 expression. Finally, we examined the effect of 5-aza-2′-deoxycytidine (5-Aza-dC) on sulfatase activity and drug-induced apoptosis. Results: SULF1 mRNA was downregulated in nine of eleven HCC cell lines, but only in six of ten primary tumors. SULF1 mRNA correlated with protein expression. Gene copy number assessment by fluorescence in situ hybridization showed intact SULF1 alleles in low-SULF1-expressing cell lines. CpG island methylation in the SULF1 promoter and two downstream CpG islands did not show an inverse correlation between DNA methylation and SULF1 expression. However, chromatin immunoprecipitation showed that the SULF1 promoter acquires a silenced chromatin state in low-SULF1-expressing cells through an increase in di/trimethyl-K9H3 and trimethyl-K27H3 and a concomitant loss of activating acetyl K9, K14H3 marks. 5-Aza-dC restored SULF1 mRNA expression in SULF1-negative cell lines, with an associated increase in sulfatase activity and sensitization of HCC cells to cisplatin-induced apoptosis. Conclusion: SULF1 gene silencing in HCC occurs through histone modifications on the SULF1 promoter. Restoration of SULF1 mRNA expression by 5-Aza-dC sensitized HCC cells to drug-induced apoptosis.

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Metabolic alterations and vulnerabilities in hepatocellular carcinoma

Gastroenterology Report ◽

10.1093/gastro/goaa066 ◽

2020 ◽

Author(s):

Daniel G Tenen ◽

Li Chai ◽

Justin L Tan

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Current Literature ◽

Primary Site ◽

The Body ◽

Therapeutic Interventions ◽

Metabolic Alterations ◽

Underlying Mechanisms ◽

Serious Disease ◽

Hcc Cells

Abstract Liver cancer is a serious disease. It is ranked as the cancer with the second highest number of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC), which arises from transformed hepatocytes, is the major subtype of liver cancer. It accounts for 85% of total liver-cancer cases. An important aspect of HCC that has been actively studied is its metabolism. With the liver as the primary site of numerous metabolic processes in the body, it has been shown that the metabolism of HCC cells is highly dysregulated compared to that of normal hepatocytes. It is therefore crucial to understand the metabolic alterations caused by HCC and the underlying mechanisms for these alterations. This deeper understanding will allow diagnostic and therapeutic advancements in the treatment of HCC. In this review, we will summarize the current literature in HCC metabolic alterations, induced vulnerabilities, and potential therapeutic interventions.

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TUG1 Promotes the Expression of IFITM3 in Hepatocellular Carcinoma by Competitively Binding to miR-29a

10.21203/rs.3.rs-70822/v1 ◽

2020 ◽

Author(s):

Qian Feng ◽

Weiwei Liu ◽

Wenjun Liao ◽

Jun Gao ◽

Jiyuan Ai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Liver Cancer ◽

Cancer Cells ◽

Cell Invasion ◽

Human Liver ◽

Target Gene ◽

Liver Cancer Cells ◽

Tumor Tissues ◽

Hcc Cells

Abstract Background: Numerous studies have demonstrated the important relationship of TUG1 with tumorigenesis. The present study investigated the role of TUG1 and its downstream genes miR-29a and IFITM3 in the occurrence and development of hepatocellular carcinoma (HCC). We found that both TUG1 and IFITM3 genes are highly expressed in HCC, whereas the expression of miR-29a is low in HCC. Downregulation of TUG1 reduces cell invasion, metastasis, and cell proliferation ability and promotes cell apoptosis. Simultaneous downregulation of miR-29a reverses this effect. Moreover, IFITM3, as the target gene of miR-29a, is positively regulated by TUG1. However, the adjustment relationship between these three components is still unknown and thus warrants further investigation. The present study investigated the regulatory relationship between TUG1, miR-29a, and IFITM3 in human liver cancer.Methods: The expression of TUG1 and miR-29a in tumor tissues and adjacent non-tumor tissues of 65 patients with HCC was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The migration and invasion of liver cancer cells were studied by the wound healing assay and the Transwell method, respectively. The apoptosis rate of HCC cells was detected by flow cytometry, and the proliferation rate of hepatoma cells was detected by the 5-ethynyl-2′-deoxyuridine (EDU) method. Immunofluorescence was used to detect the expression of TUG1 and IFITM3 in HCC-LM3 and HL-7702 cell lines. The relationship between TUG1 and miR-29a was detected using a double luciferase reporter assay and fluorescence in situ hybridization (FISH). Tumors were established in vivo by subcutaneous injection of HCC cells into nude mice and injection of these cells into the tail vein. Western blotting was used to quantify the biomarkers.Results: The expression of TUG1 increased significantly in tumor tissues and HCC cells. Moreover, the expression of miR-29a in liver cancer tissues was significantly lower than that in normal human liver tissues. The expression of TUG1 in liver cancer tissue was negatively correlated with miR-29a. Knockdown of TUG1 weakened the invasion, migration, and proliferation of HCC cells, and enhanced their apoptosis. A simultaneous knockdown of miR-29a enhanced cell invasion, metastasis, and cell proliferation, whereas the apoptosis ability decreased. As a target gene of miR-29a, IFITM3 is not only negatively regulated by miR-29a, but also positively regulated by TUG1. Therefore, TUG1 regulates IFITM3 in HCC cells by competitively binding to miR-29a, thus affecting cell invasion, migration, proliferation, and apoptosis.Conclusion: As a CeRNA, TUG1 competitively binds to miR-29a to regulate IFITM3 and promote the development of liver cancer. Downregulation of TUG1 can significantly inhibit the migration, invasion, and proliferation of liver cancer cells. Based on these results, we conclude that TUG1 could serve as a key gene to improve the prognosis of patients with HCC.

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Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01912-y ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Sanghwa Kim ◽

Minji Lee ◽

Yeonhwa Song ◽

Su-Yeon Lee ◽

Inhee Choi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Er Stress ◽

Stress Responses ◽

Arginine Metabolism ◽

Tumor Spheroids ◽

Clinical Value ◽

Suppressor Activity ◽

Argininosuccinate Synthase ◽

Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids. Methods Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model. Results Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2α/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism. Conclusions These results demonstrate the critical functional roles for the arginine metabolism–independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression.

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

Cell & Bioscience ◽

10.1186/s13578-021-00585-6 ◽

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.

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

Cell Death and Disease ◽

10.1038/s41419-021-03626-7 ◽

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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