Hsa_circ_0013290 Acts as Cancer-Promoting Gene in Hepatocellular Carcinoma

Background As a new class of non-coding RNAs, circRNAs have been recently reported to be involved in the tumorigenesis and progression of human cancers. In the current study, we attempted to explore the potential function of a novel circRNA (hsa_circ_0013290) in hepatocellular carcinoma (HCC). Methods Relative hsa_circ_0013290 expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The subcellular location of hsa_circ_0013290 was performed by RNA subcellular isolation and fluorescence in situ hybridization (FISH) assays. The effect of hsa_circ_0013290 on proliferation was detected by Cell Counting Kit-8 (CCK-8) assays. The effect of hsa_circ_0013290 on cell cycle distribution and apoptosis was detected by flow cytometry. The invasion and migration abilities of hsa_circ_0013290 were detected by transwell assays. Results Hsa_circ_0013290 is significantly upregulated in HCC cell lines and mainly located in cytoplasm of HCC cells. Hsa_circ_0013290 overexpression promotes cell invasion and migration and inhibits cell apoptosis. In contrast, hsa_circ_0013290 knockdown impedes cell invasion and migration and accelerates cell apoptosis. However, hsa_circ_0013290 did not affect cell proliferation. Conclusions Hsa_circ_0013290 is overexpressed in HCC cell lines and is mainly located in the cytoplasm of HCC cells. Hsa_circ_0013290 promotes cell invasion and migration, and inhibits cell apoptosis.

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LINC00844 promotes proliferation and migration of hepatocellular carcinoma by regulating NDRG1 expression

PeerJ ◽

10.7717/peerj.8394 ◽

2020 ◽

Vol 8 ◽

pp. e8394 ◽

Cited By ~ 1

Author(s):

Wei Zhou ◽

Kang Huang ◽

Qiuyan Zhang ◽

Shaojun Ye ◽

Zibiao Zhong ◽

...

Keyword(s):

Prostate Cancer ◽

Hepatocellular Carcinoma ◽

Cell Lines ◽

Cell Invasion ◽

Quantitative Polymerase Chain Reaction ◽

The Cancer Genome Atlas ◽

Cell Counting ◽

Migration And Invasion ◽

Aberrant Expression ◽

And Migration

Background Aberrant expression of long noncoding RNAs are implicated in the pathogenesis of human malignancies. LINC00844 expression is dramatically downregulated in prostate cancer, and functional studies have revealed the association between the aberrant expression of LINC00844 and prostate cancer cell invasion and metastasis. However, the function and mechanism of action of LINC00844 in the pathogenesis of hepatocellular carcinoma (HCC) are poorly understood. Methods LINC00844 and N-Myc downstream-regulated 1 (NDRG1) expression in HCC tissues and cell lines was detected with real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Correlations between LINC00844 expression level and clinicopathological features were investigated using the original data from The Cancer Genome Atlas (TCGA) database. HepG2 and HCCLM9 cell lines were transfected with Lv-LIN00844 virus to obtain LINC00844-overexpressing cell lines. Cell proliferation and cell invasion and migration were examined with the cell counting kit-8 (CCK-8) and transwell assay, respectively. Furthermore, the correlation between LINC00844 and NDRG1 expression was analysed using Pearson’s correlation analysis. Results LINC00844 expression was significantly downregulatedin HCC tissues and cell lines, and a statistical correlation was detected between low LINC00844 expression and sex (Female), advanced American Joint Committee on Cancer (AJCC) stage (III + IV), histological grade (G3 + G4), and vascular invasion (Micro and Macro). In vitro experiments showed that LINC00844 overexpression significantly repressed the proliferation, migration, and invasion of HCC cells. NDRG1 expression was higher in HCC tissues and LINC00844 could partly inhibit the expression of NDRG1.

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

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2114 ◽

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.

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MiR-3150b inhibits hepatocellular carcinoma cell proliferation, migration and invasion by targeting GOLPH3

Journal of Investigative Medicine ◽

10.1136/jim-2019-001181 ◽

2019 ◽

Vol 68 (3) ◽

pp. 770-775

Author(s):

Yi Zhang ◽

Jianjun Wang ◽

Hongling Su

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Carcinoma Cell ◽

Cell Counting ◽

Luciferase Assay ◽

Migration And Invasion ◽

Invasion And Migration ◽

Hepatocellular Carcinoma Cell ◽

And Migration ◽

Hcc Cells

BackgroundIn this study, we aimed to explore the potential involvement of miR-3150b in hepatocellular carcinoma (HCC) carcinogenesis.MethodsThe expression of miR-3150b and Golgi phosphoprotein 3 (GOLPH3) was determined in HCC cell lines. Cell proliferation, migration and invasion were estimated by Cell Counting Kit-8, wound healing and Transwell assays. The association between miR-3150b and GOLPH3 was verified by luciferase assay.ResultsMiR-3150b was downregulated, while GOLPH3 was remarkably upregulated in HCC cells. Furthermore, miR-3150b inhibited HCC cell proliferation, migration and invasion. MiR-3150b directly targeted and negatively regulated GOLPH3.ConclusionMiR-3150b suppressed HCC cell proliferation, invasion and migration by targeting GOLPH3.

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MicroRNA-197 Promotes Metastasis of Hepatocellular Carcinoma by Activating Wnt/β-Catenin Signaling

Cellular Physiology and Biochemistry ◽

10.1159/000495242 ◽

2018 ◽

Vol 51 (1) ◽

pp. 470-486 ◽

Cited By ~ 8

Author(s):

Zhaoxia Hu ◽

Peipei Wang ◽

Jiaxin Lin ◽

Xingrong Zheng ◽

Fangji Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Cell Invasion ◽

Invasion And Migration ◽

Report System ◽

And Migration ◽

Signaling Activation

Background/Aims: MicroRNA-197 (miR-197) has been shown to play roles in epithelialmesenchymal transition (EMT) and metastasis. The Wnt/β-catenin pathway is associated with EMT, but whether miR-197 regulatesWnt/β-catenin remains unclear. This study was to demonstrate the role of miR-197 on the Wnt/β-catenin pathway in hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-197 in 105 HCC specimens and 15 HCC cell lines. We tested the predicted target gene of miR-197 using a genetic report system. The role of miR-197 in HCC cell invasion and migration (wound healingand cell invasion and migrationby Transwell assays) and in an HCC xenograft modelwas analyzed. Results: Using a miRNA microarray analysis of HCC specimens and compared with non-metastatic HCC, miR-197 was identified as one of the most upregulated miRNAs in metastatic HCC. miR-197 expression was positively associated with the invasiveness of HCC cell lines. Metastatic HCC cells with high miR-197 expression had Wnt/β-catenin signaling activation. High levels of miR-197 expression also promoted EMT and invasionHCC cells in vitro and in vivo. miR-197 directly targeted Axin-2, Naked cuticle 1 (NKD1), and Dickkopf-related protein 2 (DKK2), leading to inhibition of Wnt/β-catenin signaling. High miR-197 expression was found in HCC specimens from patients with portal vein metastasis;high miR-197 expression correlated to the expression of Axin2, NKD1, and DKK2. Conclusion: miR-197 promotes HCC invasion and metastasis by activating Wnt/β-catenin signaling. miR-197 could possibly be used as a prognostic marker and therapeutic target for HCC.

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miR-940 Suppresses Tumor Cell Invasion and Migration via Regulation of CXCR2 in Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2016/7618342 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Dong Ding ◽

Yaodong Zhang ◽

Renjie Yang ◽

Xing Wang ◽

Guwei Ji ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Pcr Analysis ◽

Poor Overall Survival ◽

Invasion And Migration ◽

Kaplan Meier ◽

And Migration ◽

Edmondson Grade ◽

Hcc Cells

Aim. To investigate the expression of miR-940 in the hepatocellular carcinoma (HCC) and its impact on function and biological mechanism in the HCC cells.Methods. Quantitative RT-PCR analysis was used to quantify miR-940 expression in 46 cases of tissues and cells. Transfection of HCC cell lines was performed by miR-940 mimics; the abilities of invasion and migration were assessed through Transwell array. Western blot represents the alteration in expression of CXCR2 by miR-940 mimics.Results. miR-940 expression was decreased significantly in the HCC tissues and the relevant cell lines. miR-940 upregulation suppressed the invasion and migration of HCC cells in vitro. Furthermore, the CXCR2 was downregulated to suppress invasion and migration after miR-940 mimics. Moreover, decreased miR-940 expression was negatively correlated with Edmondson grade (P=0.008), tumor microsatellite or multiple tumors (P=0.04), vascular invasion (P=0.035), and recurrence and metastasis (P=0.038). Kaplan-Meier analysis demonstrated that decreased miR-940 expression contributed to poor overall survival (P<0.05).Conclusions. Our findings present that miR-940 acts as a pivotal adaptor of CXCR2 and its transcription downregulated CXCR2 expression to decrease HCC invasion and migration in vitro. Our study suggests that miR-940 may be a novel poor prognostic biomarker for HCC.

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TO901317 inhibits the development of hepatocellular carcinoma by LXRα/Glut1 decreasing glycometabolism

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00061.2018 ◽

2019 ◽

Vol 316 (5) ◽

pp. G598-G607 ◽

Cited By ~ 5

Author(s):

Ting Xiong ◽

Zihan Li ◽

Xuelong Huang ◽

Kaiqiang Lu ◽

Weiquan Xie ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Western Blot ◽

Cell Invasion ◽

Glucose Concentration ◽

Glucose Transporter ◽

Liver X Receptor ◽

Invasion And Migration ◽

And Migration ◽

Hcc Cells

This study was conducted to observe the effect and possible mechanism of TO901317 in vivo and in vitro to provide a new basis for the targeted therapy of hepatocellular carcinoma (HCC). The expressions of liver X receptor (LXR)-α, glucose transporter (Glut)-1, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase (MMP)-9 were analyzed from HCC public database (NCBI PubMed database). The result showed that LXRα was downregulated, whereas Glut1, PCNA, and MMP9 were upregulated in human HCC compared with normal liver. Furthermore, LXRα mRNA was negatively correlated with Glut1 mRNA. At the same time, HCC cells were cultivated in vitro and axillary injected in nude mice to establish the xenograft model. The xenograft in the TO901317-treated group was slower and smaller than the control group. The protein expression of LXRα, Glut1, and MMP9 could be detected by Western blot and glucose level. As a result, TO901317 could inhibit the cell proliferation of HCC in a dose-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. With the increase of TO901317 concentration, the cellular glucose concentration and ATP level were gradually decreased. Western blot results showed TO901317 could upregulate LXRα expression but downregulate MMP9 and Glut1 expression. Transwell and wound-healing analysis confirmed that, by increasing the concentration of TO901317, the cell invasion and migration were both decreased. LXRα small-interfering RNA (siRNA) could relieve the suppression effect of TO901317 on the cell invasion and migration and the expression of LXRα, Glut1, and MMP9. The glucose concentration was also raised. TO901317 could repress the progress of HCC cells by reducing the glucose concentration, upregulating LXRα expression, but downregulating the expression of Glut1 and MMP9. NEW & NOTEWORTHY This subject confirmed that TO901317, a specific liver X receptor agonist, could inhibit the progression of liver cancer through upregulating liver X receptor-α, downregulating the expression of glucose transporter-1 and matrix metalloproteinase-9, and decreasing the glucose content in SMMC-7721 and HepG2 cells.

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MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells

Pharmacology ◽

10.1159/000477667 ◽

2017 ◽

Vol 100 (5-6) ◽

pp. 269-282 ◽

Cited By ~ 25

Author(s):

Bin Xu ◽

Tangpeng Xu ◽

Huali Liu ◽

Qian Min ◽

Shidong Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Cell Counting ◽

Luciferase Assay ◽

Smad Signaling ◽

Invasion And Migration ◽

Qrt Pcr ◽

And Migration ◽

Hcc Cells

Objective: To verify that miR-490-5p could influence hepatocellular carcinoma (HCC) cells' proliferation, invasion, cycle, and apoptosis by targeting BUB1. Methods: Quantitative real time-PCR (QRT-PCR) was used to determine the miR-490-5p expression. Immunohistochemistry, qRT-PCR, and Western blot were employed to detect BUB1 and transforming growth factor-beta (TGFβ/Smad) signaling-related proteins expression in hepatic tissues and cells. The luciferase assay was used to confirm the targeting relationship between miR-490-5p and BUB1. The Cell Counting Kit-8, colony formation, Transwell invasion, scratch healing assays, and flow cytometry analysis were conducted to evaluate HCC cells proliferation, invasion, migration, and apoptosis alteration after transfection. Results: In HCC tissues and cells, lower expression of miR-490-5p was detected, while BUB1 was overexpressed than controls. The upregulation of miR-490-5p inhibited BUB1 expression and the overexpression of miR-490-5p or the under-expression of BUB1 inhibited HCC cells proliferation, migration, invasion, and increased the apoptosis rate. Conclusion: MiR-490-5p could regulate TGFβ/Smad signaling pathways by inhibiting BUB1, which could then inhibit HCC cells proliferation, invasion, and migration as well as decrease cell viability and increase apoptosis.

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Downregulation of Heparanase Expression Results in Suppression of Invasion, Migration, and Adhesion Abilities of Hepatocellular Carcinoma Cells

BioMed Research International ◽

10.1155/2015/241983 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

Xiao-Peng Chen ◽

Jun-Sheng Luo ◽

Ye Tian ◽

Chen-Lin Nie ◽

Wei Cui ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Invasion ◽

Malignant Tumors ◽

Carcinoma Cells ◽

Adherence Rate ◽

Rt Pcr ◽

Invasion And Migration ◽

Normal Hepatocyte ◽

And Migration ◽

Hcc Cells

Objective.Heparanase (HPSE) is high-expressed in most malignant tumors including hepatocellular carcinoma (HCC) and promotes cancer cell invasion and migration. The aim of the study is to explore whether HPSE enhances adhesion in metastasis of HCC cells.Methods. HPSE expressions in human HCC cells were measured with real-time RT-PCR and Western blot analysis. Four recombinant miRNA vectors pcDNATM6.2-GW/EmGFP-miR-HPSE (pmiR-HPSE) were transfected into HCCLM3 cell. HPSE expression in transfected cell was measured. The cell invasion, migration, and adhesion abilities were detected, respectively.Results. Both HPSE mRNA and protein relative expression levels were higher in HepG2, BEL-7402, and HCCLM3 cells than those in normal hepatocyte (P<0.05). HPSE showed highest expression level in HCCLM3 cell (P<0.05). Transfection efficiencies of four miRNA vectors were 75%–85%. The recombinant vectors significantly decreased HPSE expression in transfected HCCLM3 cells (P<0.01), and pmiR-HPSE-1 showed best interference effect (P<0.05). pmiR-HPSE-1 significantly decreased the penetrated and migrating cells numbers and adherence rate of HCCLM3 cells (P<0.05).Conclusion. HPSE is a potentiator of cell adhesion in metastasis of HCC.

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Anti-neoplastic Effect of Ginkgolide C through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma Cells

International Journal of Molecular Sciences ◽

10.3390/ijms21218303 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8303

Author(s):

Min Hee Yang ◽

Seung Ho Baek ◽

Jae-Young Um ◽

Kwang Seok Ahn

Keyword(s):

Hepatocellular Carcinoma ◽

Invasion And Migration ◽

Oncogenic Pathways ◽

Tumor Growth And Metastasis ◽

And Migration ◽

Induced Apoptosis ◽

Interfering Rna ◽

Hepatocyte Growth ◽

Hcc Cells ◽

Met Phosphorylation

Ginkgolide C (GGC) derived from Ginkgo biloba, has been reported to exhibit various biological functions. However, the anti-neoplastic effect of GGC and its mechanisms in liver cancer have not been studied previously. Hepatocyte growth factor (HGF)/c-mesenchymal–epithelial transition receptor (c-Met) pathway can regulate tumor growth and metastasis in hepatocellular carcinoma (HCC) cells. This study aimed to evaluate the anti-neoplastic effect of GGC against HCC cells and we observed that GGC inhibited HGF-induced c-Met and c-Met downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. In addition, GGC also suppressed the proliferation of expression of diverse tumorigenic proteins (Bcl-2, Bcl-xL, Survivin, IAP-1, IAP-2, Cyclin D1, and COX-2) and induced apoptosis. Interestingly, the silencing of c-Met by small interfering RNA (siRNA) mitigated c-Met expression and enhanced GGC-induced apoptosis. Moreover, it was noted that GGC also significantly reduced the invasion and migration of HCC cells. Overall, the data clearly demonstrate that GGC exerts its anti-neoplastic activity through modulating c-Met phosphorylation and may be used as an effective therapy against HCC.

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MiR-486-5p Suppresses Proliferation and Migration of Hepatocellular Carcinoma Cells through Downregulation of the E3 Ubiquitin Ligase CBL

BioMed Research International ◽

10.1155/2019/2732057 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9

Author(s):

Jia He ◽

Bin Xiao ◽

Xiaoyan Li ◽

Yongyin He ◽

Linhai Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Ubiquitin Ligase ◽

Target Genes ◽

E3 Ubiquitin Ligase ◽

Tumor Stage ◽

Suppressor Gene ◽

Cell Counting ◽

And Migration ◽

Proliferation And Migration

MicroRNAs have been broadly implicated in cancer, but precise functions and mechanisms in carcinogenesis vary among cancer types and in many cases remain poorly understood. Hepatocellular carcinoma (HCC) is among the most frequent and lethal cancers. The aim of the present study was to investigate the role of miR-486-5p in HCC and identify its specific target. MiR-486-5p was significantly downregulated in HCC tissues and cell lines compared with noncancerous tissues and, respectively, although expression level was not correlated with the degree of infiltration or tumor stage. However, miR-486-5p overexpression in HCC cells inhibited proliferation and migration as evidenced by CCK-8 cell counting, wound healing, and transwell assays, indicating that miR-486-5p is an HCC suppressor. We employed four miRNA databases to predict the target genes of miR-486-5p and verified retrieved genes using qPCR and western blotting. The E3 ubiquitin ligase CBL was significantly downregulated by miR-486-5p overexpression in HCC cell lines at both mRNA and protein level, and overexpression of CBL counteracted the inhibitory effects of miR-486-5p on HCC cell proliferation and migration. Moreover, CBL expression was negatively correlated with miR-486-5p expression in HCC tissues. Collectively, our results suggest that miR-486-5p may act as a tumor suppressor gene in HCC by downregulating CBL expression.

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