scholarly journals MicroRNA-361-5p Inhibits Cancer Cell Growth by Targeting CXCR6 in Hepatocellular Carcinoma

2016 ◽  
Vol 38 (2) ◽  
pp. 777-785 ◽  
Author(s):  
Jian-Jun Sun ◽  
Guo-Yong Chen ◽  
Zhan-Tao Xie
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nude Mice ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Western Blots ◽  
Normal Tissues ◽  
Proliferation And Invasion ◽  
Hcc Cells

Background/Aims: A growing body of evidence supports the notion that MicroRNAs (miRNAs) function as key regulators of tumorigenesis. In the present study, the expression and roles of miRNA-361-5p were explored in hepatocellular carcinoma (HCC). Methods: Quantitative real-time PCR was used to detect the expression miR-361-5p in HCC tissues and pair-matched adjacent normal tissues. MTT and BrdU assays were used to identify the role of miR-361-5p in the regulation of proliferation and invasion of HCC cells. Using bioinformatics analysis, luciferase reporter assays and Western blots were used to identify the molecular target of miR-361-5p. nude mice were used to detect the anti-tumor role of miR-361-5p in vivo. Results: miR-361-5p was down-regulated in HCC tissues in comparison to adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-361-5p suppressed proliferation and invasion of HCC cells. Chemokine (C-X-C Motif) receptor 6 (CXCR6) was identified as a target of miR-361-5p. Indeed, knockdown of CXCR6 photocopied, while overexpression of CXCR6 largely attenuated the anti-proliferative effect of miR-361-5p. More importantly, in vivo studies demonstrated that forced expression of miR-361-5p significantly inhibited tumor growth in the nude mice. Conclusion: Our results indicate that miR-361-5p acts as a tumor suppressor and might serve as a novel therapeutic target for the treatment of HCC patients.

scholarly journals Long non-coding RNA LINC00641 promotes the growth and invasiveness of hepatocellular carcinoma by antagonizing miR-501-3p

2021 ◽  
Author(s):  
Haitao Xie ◽  
Hui Zhou ◽  
Yan Jiang ◽  
Wenqian Xu ◽  
Leping Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Normal Liver ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Proliferation And Invasion ◽  
Hcc Cells

IntroductionLong non-coding RNA LINC00641 has been reported to regulate tumor progression in several cancers. However, the expression and function of LINC00641 in hepatocellular carcinoma (HCC) is still unclear.Material and methodsIn this study, we measured the expression of LINC00641 in 79 pairs of HCC and adjacent normal liver tissues. The clinical significance of LINC00641 in HCC was explored. We also investigated the function of LINC00641 in HCC proliferation and invasion.ResultsWe observed that LINC00641 expression was significantly increased in HCC relative to normal tissues (P < 0.0001). High expression of LINC00641 was significantly associated with vascular invasion, advanced TNM stage, and reduced overall survival in HCC patients. Knockdown of LINC00641 inhibited the proliferation, colony formation, and invasion of HCC cells. In contrast, overexpression of LINC00641 promoted HCC cell growth and invasiveness. In vivo studies confirmed that knockdown of LINC00641 restrained tumorigenesis of HCC cells. Mechanistic studies revealed that LINC00641 inhibited the expression of miR-501-3p, which has been previously reported to act as a tumor suppressor in HCC. Furthermore, luciferase reporter assays validated that LINC00641 harbored a target site for miR-501-3p. Rescue experiments demonstrated that LINC00641-induced proliferation and invasion of HCC cells was reversed by co-expression of miR-501-3p.ConclusionsTaken together, LINC00641 contributes to aggressive phenotype of HCC cells by sponging miR-501-3p and represents a promising therapeutic target for this disease.

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 Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chenwei Wang ◽  
Yadi Liao ◽  
Wei He ◽  
Hong Zhang ◽  
Dinglan Zuo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Tissue Microarrays ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Hcc Cells

Abstract Background Elafin is a serine protease inhibitor critical for host defence. We previously reported that Elafin was associated with the recurrence of early-stage hepatocellular carcinoma (HCC) after surgery. However, the exact role of Elafin in HCC remains obscure. Methods HCC tissue microarrays were used to investigate the correlation between Elafin expression and the prognosis of HCC patients. In vitro migration, invasion and wound healing assays and in vivo lung metastasis models were used to determine the role of Elafin in HCC metastasis. Mass spectrometry, co-immunoprecipitation, western blotting, and immunofluorescence staining assays were performed to uncover the mechanism of Elafin in HCC. Dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the transcriptional regulation of Elafin. Results Elafin expression was frequently increased in HCC tissues compared to normal tissues, and high Elafin expression in HCC tissues was correlated with aggressive tumour phenotypes and a poor prognosis in HCC patients. Elafin dramatically enhanced the metastasis of HCC cells both in vitro and in vivo by interacting with EGFR and activating EGFR/AKT signalling. Moreover, Elafin attenuated the suppressive effects of erlotinib on HCC metastasis. Besides, Elafin was transcriptionally regulated by Sp1 in HCC cells. Clinically, Elafin expression was positively correlated with Sp1, Vimentin, and EGFR signalling in both our HCC tissue microarrays and TCGA database analysis. Conclusions Upregulation of Elafin by Sp1 enhanced HCC metastasis via EGFR/AKT pathway, and overexpression of Elafin attenuated the anti-metastatic effects of erlotinib, suggesting a valuable prognostic biomarker and therapeutic target for HCC.

scholarly journals KLF7/VPS35 Axis Contributes to Hepatocellular Carcinoma Progression through CCDC85C-activated β Catenin Pathway

2020 ◽  
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. Human HCC tissues were collected to study the clinical significance VPS35 and β-catenin. Results: Firstly, 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. 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.

scholarly journals LncRNA-URHC Functions as a ceRNA to Regulate Danjb9 Expression by Competitively Binding to miR-5007-3p in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
kunwei niu ◽  
Shibin Qu ◽  
Xuan Zhang ◽  
Jimin Dai ◽  
Jianlin Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Underlying Mechanisms ◽  
Proliferation In Vitro ◽  
Hcc Cells

Abstract Background: Hepatocellular carcinoma (HCC) is often diagnosed at a late stage, when the prognosis is poor. The regulation of long non-coding RNAs (lncRNAs) plays a crucial role in HCC. However, the precise regulatory mechanisms of lncRNA signaling in HCC remain largely unknown. We study aim to investigate the underlying mechanisms of lncRNA (upregulated in hepatocellular carcinoma) URHC in HCC. Methods: RT-qPCR, fluorescence in situ hybridization (FISH) staining, EdU, colony formation, and tumor xenografts experiments were used to identify localized and biological effects of URHC on HCC cells in vitro and in vivo. The bioinformatics analysis, Dual-luciferase reporter assay, and rescue experiments revealed the potential mechanism of URHC.Results: URHC silencing may inhibit the HCC cells proliferation in vitro and in vivo. We found that URHC was mainly localized in the cytoplasm. The expression of miR-5007-3p was negatively regulated by URHC. And miR-5007-3p could reverse the effect of URHC in HCC cells. The expression of DNAJB9 was negatively regulated by miR-5007-3p but positively regulated by URHC. These suggesting of lncRNA-URHC positively regulated the level of DNAJB9 by sponging miR-5007-3p.Conclusion: Together, our study elucidated the role of URHC as a miRNA sponge in HCC, and shed new light on lncRNA-directed diagnostics and therapeutics in HCC.

scholarly journals MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma

2020 ◽  
Vol 40 (10) ◽  
Author(s):  
Xiaohui Duan ◽  
Wei Li ◽  
Peng Hu ◽  
Bo Jiang ◽  
Jianhui Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tumor Growth ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Hcc Cells

Abstract Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. The present study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related microRNA (miRNA), in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan–Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via Cell Counting Kit-8 (CCK8) assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights into understanding the role of miR-183-5p in HCC.

scholarly journals Circular RNA hsa_circ_0013958 Functions as an Oncogenic Gene Through Modulating miR-532-3p/WEE1 Axis in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Ma ◽  
Yue Ma ◽  
Yongjun Du ◽  
Zhongheng Wei ◽  
Jianchu Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Polymerase Chain ◽  
Oncogenic Gene ◽  
Proliferation And Invasion

Backgroundcirc0013958 was identified as a biomarker, which can be used for the diagnosis and screening of lung cancer. However, the role of circ0013958 in hepatocellular carcinoma (HCC) remains unclear.MethodsIn our study, quantitative real-time polymerase chain reaction was performed to determine the levels of circ0013958 in HCC tissues and cell lines. EdU, CCK-8, transwell, flow cytometry and tumorigenesis assays were applied to assess the functions of circ0013958 in HCC in vitro and in vivo. Western blot assay was to detect the expression of WEE1. Luciferase reporter assay, bioinformatics analysis and rescue experiments were used to examine the interaction among circ0013958, miR-532-3p and WEE1.ResultsIt revealed that circ0013958 was significantly up-regulated in HCC, which was positively correlated with poor prognosis of HCC patients. Circ0013958 promoted HCC cell proliferation and invasion, inhibited cell apoptosis in vitro, and promoted tumorigenesis in vivo. Circ0013958 acted as a miR-532-3p sponge to regulate WEE1 expression, thus promoting the progression of HCC.ConclusionsCirc0013958 promotes HCC progression through miR-532-3p/WEE1 axis. Circ0013958 may serve as a potential diagnostic biomarker and therapeutic target of HCC.

scholarly journals microRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Wenjie Huang ◽  
Sufen Li ◽  
Xianhua Chen ◽  
Lin Sun ◽  
Gangxi Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Cellular Models ◽  
Hcc Cells

Abstract BackgroundIncreasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. MethodsWe carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.ResultsThis study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusionour study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.

scholarly journals MicroRNA-1915-3p Promotes Cell Metastasis and Progression by Targeting Bcl2L11 in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Wenjie Huang ◽  
Sufen Li ◽  
Xianhua Chen ◽  
Lin Sun ◽  
Gangxi Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
In Vivo Studies ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Cellular Models ◽  
Hcc Cells

Abstract Background: Increasing evidence suggests that miR-1915-3p plays vital regulatory roles in metastasis and progression of several types of cancer. However, the roles and underlying mechanism of miR-1915-3p in hepatocellular carcinoma (HCC) remains largely unclear. Methods: We carried out a bioinformatic meta-analysis to investigate a possible role of miR-1915-3p as prognostic biomarkers. In vitro cellular models of HCC were used for functional studies exploring the role of miR-1915-3p in HCC development and progression. Finally, in vivo studies were performed to demonstrate that miR-1915-3p is a viable therapeutic target.Results: This study showed that miR-1915-3p was significantly increased in HCC tissue samples and cell lines, and high miR-1915-3p expression was associated with a poor overall survival (OS) and disease-free survival (DFS) time of HCC patients. Overexpression or ablation of miR-1915-3p expression resulted in accelerated or inhibited cell proliferation, migration, and invasion respectively in HCC cells. In addition, miR-1915-3p induced downregulation of proapoptotic factors, including caspase3, caspase8, BAD, Bcl2L11, and P53. It also induced upregulation of antiapoptotic Bcl-2, protecting HCC cells from apoptosis. A biological analysis indicated that miR-1915-3p could be directly targeted to Bcl2L11 to regulate the proliferation, invasion, and migration of HCC cells. Furthermore, in vivo studies confirmed that treatment with miR-1915-3p retarded the growth of tumor in nude mice. Conclusion: our study provided the evidence for the regulatory role of miR-1915-3p in HCC, which was causally linked to targeting of Bcl2L11. Medications that abrogate excessively expressed miR-1915-3p may offer novel targets for the management of HCC.

Sign in / Sign up

Export Citation Format

Share Document