Long non‐coding RNA VPS9D1-AS1 facilitates cell proliferation, migration and stemness in hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is a common cancer leading to high morbidity and mortality in worldwide. Previous studies revealed that SEC61 translocon alpha 1 subunit1 (SEC61A) can act as an oncogene in colon adenocarcinoma. However, the functions and molecular mechanism associated with HCC progression remain to be explored. This study aimed at exploring the role of SEC61A1 in HCC progression. Methods EdU assay and colony formation assay were applied to assess cell proliferation. The migratory ability of transfected HCC cells was evaluated by transwell migration assay. Sphere formation assay was used to detect the stemneess of HCC cells. Bioinformatics analysis tools and mechanism experiments were used to predict and analyze the potential molecular mechanism associated with the upregulation of SEC61A1 in HCC cells. Results Up-regulated SEC61A1 facilitated cell proliferation, migration and stemness in HCC cells. MiR-491-5p negatively regulated SEC61A1 and inhibited HCC cell proliferation and migration by targeting SEC61A1. VPS9D1 antisense RNA 1 (VPS9D1-AS1) could up-regulate SEC61A1 through sponging miR-491-5p. Early growth response 1 (EGR1) was identified as the upstream transcriptional activator for both SEC61A1 and VPS9D1-AS1. Conclusions Our study unveiled a novel molecular pathway facilitating HCC cell proliferation, migration and stemness, which may shed new insight into HCC treatment.

Download Full-text

LncRNA HCG18 contributes to the progression of hepatocellular carcinoma via miR-214-3p/CENPM axis

The Journal of Biochemistry ◽

10.1093/jb/mvaa073 ◽

2020 ◽

Vol 168 (5) ◽

pp. 535-546 ◽

Cited By ~ 1

Author(s):

Yuepei Zou ◽

Zhonghua Sun ◽

Shuangming Sun

Keyword(s):

Hepatocellular Carcinoma ◽

Messenger Rna ◽

Animal Experiments ◽

Non Coding Rna ◽

Diphenyltetrazolium Bromide ◽

And Migration ◽

Hcc Cells ◽

Proliferation And Migration

Abstract Long non-coding RNA (lnc) HCG18 has been reported to contribute progression of a variety of tumours. However, its roles in hepatocellular carcinoma (HCC) remains unknown. In the current study, we intended to uncover the biological functions of HCG18 in HCC. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression of HCG18, microRNA-214-3p (miR-214-3p) and centromere protein M (CENPM) messenger RNA (mRNA). The role of HCG18 in the growth and migration were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony formation assay, wound healing assay and flow cytometry in vitro and animal experiments in vivo. The results showed that HCG18 was highly expressed in HCC tissues. HCG18 silencing inhibited the proliferation and migration while induced the apoptosis of HCC cells. Besides, miR-214-3p was down-regulated in HCC cells. Further experiments revealed that miR-214-3p could directly bind to HCG18 and exerted an anti-tumour role to counteracted siHCG18-1-mediated influence in HCC cells. Moreover, miR-214-3p could directly interact with CENPM mRNA and down-regulating the expression of CENPM. While HCG18 could up-regulate the expression of CENPM through acting as a sponge of miR-214-3p. Therefore, those results suggested HCG18 functioned as an oncogene to promote the proliferation and migration of HCC cells via miR-214-3p/CENPM axis.

Download Full-text

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

Biochemistry and Cell Biology ◽

10.1139/bcb-2019-0227 ◽

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.

Download Full-text

LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820957023 ◽

2020 ◽

Vol 19 ◽

pp. 153303382095702

Author(s):

Xue-zhen Song ◽

Xiao-ning Ren ◽

Xiao-jun Xu ◽

Xiao-xuan Ruan ◽

Yi-li Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Molecular Mechanism ◽

Cancer Progression ◽

Cell Clone ◽

Mtor Pathway ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gene Assay ◽

Hcc Cells

Hepatocellular carcinoma (HCC) is a severe disease with high mortality in the world. Emerging evidence has suggested that lncRNAs play an important role in cancer progression, including HCC. This study aimed to comprehensively investigate the effect of lncRNA RHPN1 antisense RNA 1 (RHPN1-AS1) on HCC and its underlying molecular mechanism. In this study, we evaluated the expressions of lncRNA RHPN1-AS1 and miR-7-5p by qRT-RCR in both HCC tissue and HCC cells. Our findings showed that lncRNA RHPN1-AS1 was upregulated in HCC tissue and HCC cells, while miR-7-5p was downregulated. LncRNA RHPN1-AS1 expression in HCC patients was closely related to vascular invasion, tumor-node-metastasis (TNM) stage and barcelona clinic liver cancer (BCLC) stage. Furthermore, we quantified cell clone-formation ability, proliferation, migration and invasion of HCCLM3 and MHCC97 H cells using several assays (colony formation assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay and transwell assay, respectively). Functional experiments confirmed that silencing lncRNA RHPN1-AS1 inhibited cell proliferation, migration and invasion in HCCLM3 and MHCC97 H cells. After that, bioinformatics analysis, dual luciferase reporter gene assay, qRT-PCR and western blot were used to investigate the molecular mechanism of lncRNA RHPN1-AS1 on HCC. Mechanistically, the rescue experiments demonstrated that miR-7-5p inhibitor reversed the inhibition effect of silencing lncRNA RHPN1-AS1 on HCCLM3 cells proliferation, migration and invasion. Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.

Download Full-text

Functional analysis of miR-101-3p and Rap1b involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis

Biochemistry and Cell Biology ◽

10.1139/bcb-2013-0128 ◽

2014 ◽

Vol 92 (2) ◽

pp. 152-162 ◽

Cited By ~ 21

Author(s):

Yanrui Sheng ◽

Shijia Ding ◽

Ke Chen ◽

Juan Chen ◽

Sen Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Promoter Activity ◽

Down Regulation ◽

B Virus ◽

And Migration ◽

Hcc Cells ◽

Proliferation And Migration

MicroRNA-101(miR-101) has been shown to be down-regulated in hepatocellular carcinoma (HCC). The hepatitis B virus (HBV) is a major risk factor in the development and progression of HCC. However, the correlation between HBV and miR-101 has not yet been fully elucidated. In this study, we reported that HBV could repress miR-101-3p by inhibiting its promoter activity and identified the potential effects of miR-101-3p on some important biological properties of HCC cells by targeting Rap1b. Dual-luciferase reporter assays showed that HBV down-regulated miR-101-3p by inhibiting its promoter activity. Down-regulation of miR-101-3p promoted cell proliferation, migration, and reduced apoptosis, and resulted in up-regulation of Rap1b, while overexpression of miR-101-3p inhibited these processes. Moreover, overexpression of Rap1b was able to reverse the suppressed cell proliferation and migration mediated by miR-101-3p. Our data showed that HBV down-regulated miR-101-3p expression by inhibiting its promoter activity, which resulted in up-regulation of Rap1b, and down-regulation of miR-101-3p or up-regulation of Rap1b promoted proliferation and migration of HCC cells. This provides a new understanding of the mechanism of HBV-related HCC pathogenesis and the potential application of miR-101-3p in cancer therapy.

Download Full-text

Knockdown of SLC34A2 Inhibits Hepatocellular Carcinoma Cell Proliferation and Invasion

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504016x14719078133483 ◽

2016 ◽

Vol 24 (6) ◽

pp. 511-519 ◽

Cited By ~ 10

Author(s):

Yanhua Li ◽

Xia Chen ◽

Hong Lu

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Underlying Mechanism ◽

Mesenchymal Transition ◽

Human Carcinomas ◽

And Migration ◽

Proliferation And Invasion ◽

Hcc Cells

The gene solute carrier family 34 (sodium phosphate), member 2 (SLC34A2), is a member of the SLC34 family. Increasing evidence suggests that SLC34A2 is involved in the development of many human carcinomas. However, its role in hepatocellular carcinoma (HCC) is still unclear. Therefore, in this study we investigated the role of SLC34A2 in HCC and explored the underlying mechanism. We found that the expression of SLC34A2 is upregulated in HCC cell lines. Knockdown of SLC34A2 obviously inhibited HCC cell proliferation, migration/invasion, and the epithelial‐mesenchymal transition (EMT) phenotype. Furthermore, knockdown of SLC34A2 significantly inhibited the expression of phosphorylated PI3K and AKT in HCC cells. Taken together, these results suggest that knockdown of SLC34A2 inhibits proliferation and migration by suppressing activation of the PI3K/AKT signaling pathway in HCC cells, and SLC34A2 may be a potential therapeutic target for the treatment of HCC.

Download Full-text

In Hepatocellular Carcinoma, miRNA-296-3p Targets MSL2 and Suppresses Cell Proliferation and Invasion

Journal of Oncology ◽

10.1155/2021/7430468 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Xiaocui Li ◽

Min An ◽

Zhenjun Gao

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Flow Cytometric Analysis ◽

Cancer Control ◽

Luciferase Reporter ◽

Protein Levels ◽

Repressive Effect ◽

And Migration ◽

New Research ◽

Hcc Cells

Hepatocellular carcinoma (HCC) is the third-highest cause of cancer-related death in the world. miRNAs have a role in cell division, differentiation, and death biological processes. They are typically dysregulated in cancers, affecting tumor progression. miRNA-296-3p appears to play a crucial role in cancer control, according to new research. However, its expression and roles in HCC are unknown. This study used qRT-PCR and western blotting to detect the miRNA-296-3p and male-specific lethal 2 (MSL2) expression. In addition, cell proliferation, migration, invasion, and apoptosis were studied using CCK-8, flow cytometric analysis, colony formation assay, wound healing test, and transwell assays. The results show that miRNA-296-3p is underexpressed in HCC cell lines, particularly in Huh-7 and HepG2 cells. miRNA-296-3p overexpression lowers the ability of HCC cells to proliferate, migrate, and invade while increasing cell death. Luciferase reporter experiments revealed that the MSL2 is a direct target of miRNA-296-3p. Furthermore, overexpression of miRNA-296-3p reduced MSL2 mRNA and protein levels considerably, according to our findings. Furthermore, the rescue experiments showed that the MSL2 overexpression partially blocked the inhibition effects of miRNA-296-3p mimic on the proliferation and migration of HCC cells. The above results show that miRNA-296-3p may have a repressive effect in HCC by targeting MSL2 and could be used as a therapeutic target for HCC treatment.

Download Full-text

DEAH-box polypeptide 32 promotes hepatocellular carcinoma progression via activating the β-catenin pathway

10.21203/rs.3.rs-27420/v1 ◽

2020 ◽

Author(s):

Xiaoyun Hu ◽

Guosheng Yuan ◽

Qi Li ◽

Jing Huang ◽

Xiao Cheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Tumor Growth ◽

Ectopic Expression ◽

Migration And Invasion ◽

High Morbidity ◽

Rt Pcr ◽

Mesenchymal Transition ◽

Potential Biomarker ◽

Hcc Cells

Abstract Background Hepatocellular carcinoma (HCC) is a refractory cancer with high morbidity and high mortality. It has been reported that DEAH-box polypeptide 32 (DHX32) was upregulated in several types of malignancies and predicted poor prognosis, which was associated with tumor growth and metastasis. However, the expression of DHX32 in HCC and its role in HCC progression remain largely unknown. Methods Western blot and RT-PCR assays were used to detect the expression of DHX32 and epithelial mesenchymal transition (EMT)-related genes in HCC cells. Wound-healing and Transwell invasion assays were performed to determine the effect of DHX32 and β-catenin on the migration and invasion of HCC cells. Cell proliferation was examined by EdU cell proliferation assay. Results In our study, we found that high level of DHX32 expression was associated with reduced overall survival in HCC patients. DHX32 expression was upregulated in human HCC cells and ectopic expression of DHX32 induced EMT, promoted the migration, invasion, and proliferation of HCC cells, and enhanced tumor growth. Silencing DHX32 reversed EMT, inhibited the migration, invasion, and proliferation of HCC cells, and suppressed tumor growth. RT-PCR assay revealed that DHX32 regulated the expression of CTNNB1, CCND1, COX2, MMP7, and WIF1 in HCC cells. Mechanistic investigations showed that silencing DHX32 decreased the expression of β-catenin in nucleus and β-catenin siRNA abrogated DHX32-mediated EMT, migration, invasion, and proliferation in HCC cells. Conclusions Our data suggested that DHX32 was an attractive regulator of HCC progression and indicated DHX32 can serve as a potential biomarker and therapeutic target for HCC patients.

Download Full-text

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.

Download Full-text

LncRNA MEG3 affects cell proliferation, apoptosis and migration by targeting miR-9-5p/MDK axis and activating PDK/AKT pathway in hepatocellular carcinoma

10.21203/rs.3.rs-21095/v1 ◽

2020 ◽

Author(s):

Dezhi Wu ◽

Zheng Ma ◽

Deyu Ma ◽

Qiquan Li

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Cell Lines ◽

Molecular Mechanisms ◽

Normal Liver ◽

Luciferase Reporter ◽

Akt Pathway ◽

Normal Liver Cell ◽

Non Coding Rna ◽

And Migration

Abstract Background Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) was supposed to be a tumor suppressor in various cancers. However, the role of MEG3 in hepatocellular carcinoma (HCC) and the related molecular mechanisms are not well illustrated. This study aimed to determine the biological function of MEG3 in regulating HCC cell proliferation, apoptosis and migration. Moreover, the interaction among MEG3, microRNA (miR)-9-5p and Midkine (MDK), and the activation of phosphoinositide-dependent kinase (PDK)/AKT pathway in HCC cells were examined. Methods and Results Expression of MEG3 in a series of liver cancer cell lines was detected by RT-qPCR. Luciferase reporter assay, RT-qPCR and western blot were used to determine the interaction among MEG3, miR-9-5p and MDK, and the activation of PDK/AKT pathway. Cell proliferation and apoptosis were evaluated by CCK8, flow cytometry analysis for cell cycle and apoptosis, and Caspase 3/9 activity. Cell migration was determined by wound healing assay and MMP1 expression. We found MEG3 was decreased in HCC cell lines compared with the normal liver cell line. MEG3 suppressed HCC cell proliferation and migration, and induced cell apoptosis. Further, we found MEG3 targets miR-9-5p/MDK axis and modulates PDK/AKT pathway in HCC. Conclusion Our findings demonstrated that lncRNA MEG3 affects HCC cell proliferation, apoptosis and migration through its targeting of miR-9-5p/MDK and regulating of PDK/AKT pathway. This study suggested MEG3/miR-9-5p/MDK axis as the potential therapeutic target in HCC.

Download Full-text

MiR-9-5p promotes cell proliferation and migration of hepatocellular carcinoma by targeting CPEB3

Biomarkers in Medicine ◽

10.2217/bmm-2020-0322 ◽

2021 ◽

Vol 15 (2) ◽

pp. 97-108

Author(s):

Zheyue Shu ◽

Feng Gao ◽

Qi Xia ◽

Min Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Epithelial Mesenchymal Transition ◽

Transition Process ◽

Migration And Invasion ◽

Mesenchymal Transition ◽

Promote Cell Proliferation ◽

Growth Activity ◽

And Migration ◽

Hcc Cells

Objective: This study aimed to observe the effect of miR-9-5p and CPEB3 on hepatocellular carcinoma (HCC) cells, and investigate the underlying targeting regulatory mechanism. Materials & methods: Various experiments like CCK-8, colony formation assay, wound healing assay and Transwell were performed for cancer cell activities detection, including cell proliferation, growth activity, migration and invasion. Results: MiR-9-5p was found to be highly expressed in HCC cells, while CPEB3 was poorly expressed (p < 0.05). The overexpression of miR-9-5p and the silencing of CPEB3 both could significantly promote cell proliferation, migration and invasion (p < 0.05). In addition, miR-9-5p could target to downregulate CPEB3 expression, thus accelerating cell proliferation, migration, invasion and epithelial-mesenchymal transition process in HCC. Conclusion: MiR-9-5p can target CPEB3, thereby promoting cell proliferation, migration and invasion in HCC. The axis of miR-9-5p/CPEB3 is expected to become a potential therapeutic target beneficial for HCC patients.

Download Full-text