scholarly journals TET3 Promotes HCC Proliferation And Metastasis Via lncRNA ARAP1-AS1

2021 ◽  
Author(s):  
Qiuyu Zhuang ◽  
Xuechun Xu ◽  
Zhiguo Dai ◽  
Xiaoyuan Zheng ◽  
Wuhua Guo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Demethylation ◽  
Migration And Invasion ◽  
Rna Seq ◽  
Tumor Tissues ◽  
Proliferation And Metastasis ◽  
Cancer Types ◽  
Differentially Expressed Mrna ◽  
Hcc Cells ◽  
Downstream Mediator

Abstract Background: Aberrations of DNA methylation and proteins involved in DNA methylation process have been demonstrated to be correlated with tumor malignancy and prognosis of patients. The present study aims to investigate the preliminary mechanism underlying the biological functions of a DNA demethylation enzyme TET3 during HCC proliferation and metastasis.Methods: CCK8 assay, colony formation assay and transwell assay were performed to monito cell proliferation, migration and invasion. RNA-sequencing (RNA-seq) was applied to screen the differentially expressed mRNA upon TET3 overexpression to investigate the downstream mediators of TET3 during HCC progression. The expression of TET3 or ARAP1-AS1 was examined by western blot or quantitative real-time PCR (qRT-PCR).Results: First, TET3 expression was increased in HCC tumor tissues and positively correlated with poor prognosis of HCC patients. Next, TET3 was found to promote the proliferation and metastasis of HCC cells. RNA-seq was then performed and unveiled lncRNA ARAP1-AS1, a well identified onco-lncRNA in several cancer types, as a candidate downstream mediator of TET3. The following results indicated that TET3 increased ARAP1-AS1 expression. And rescue experiments indicated that ARAP1-AS1 knockdown impaired the proliferation of HCC cells induced by TET3 overexpression.Conclusion: TET3 promoted the proliferation and metastasis of HCC cells by regulating the expression of lncRNA ARAP1-AS1.

scholarly journals Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

2019 ◽  
Vol 22 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Q. Y. Li ◽  
K. Yang ◽  
F. G. Liu ◽  
X. G. Sun ◽  
L. Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Vital Role ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

scholarly journals Histone demethylase UTX regulates glioblastoma progression through affecting periostin expression

2021 ◽  
Author(s):  
Yan Luan ◽  
Yingfei Liu ◽  
Jingwen Xue ◽  
Ke Wang ◽  
Kaige Ma ◽  
...  
Keyword(s):  
Target Genes ◽  
Interaction Analysis ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Rna Seq ◽  
Multiple Cancer ◽  
Protein Protein Interaction ◽  
Histone H3k27 ◽  
Cancer Types ◽  
Extracellular Environment

The histone H3K27 demethylase UTX participates in regulating multiple cancer types. However, less is known about the UTX function in glioblastoma (GBM). This study aims to define the effect of UTX on GBM. GEPIA2 database analysis showed that UTX expression was significantly increased in GBM and inversely correlated with survival. Knockdown UTX inhibited GBM cell proliferation, migration, and invasion while promoting apoptosis. Moreover, knockdown UTX also hampered tumor growth in the heterotopic xenograft model. RNA-seq combined with qRT-PCR and ChIP-qPCR were used to identify the target genes. The results showed that the UTX-mediated genes were strongly associated with tumor progression and the extracellular environment. Protein-protein interaction analysis suggested that periostin (POSTN) interacted with most of the other UTX-mediated genes. POSTN supplement abolished the effect of UTX knockdown in GBM cells. Furthermore, silencing UTX exhibited similar antitumor effect in patient-derived glioblastoma stem-like cells, while UTX functions were partially restored after exposing POSTN. Our findings may reveal a new insight into the onset of gliomagenesis and progression, providing a promising therapeutic strategy for GBM treatment.

scholarly journals FOXC1 Promotes HCC Proliferation and Metastasis by Upregulating DNMT3B to Induce DNA Hypermethylation of CTH Promoter

2020 ◽  
Author(s):  
Zhuoying Lin ◽  
Wenjie Huang ◽  
Qin He ◽  
Dongxiao Li ◽  
Zhihui Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Dna Hypermethylation ◽  
Cysteine Metabolism ◽  
Proliferation And Metastasis ◽  
Dnmt3b Expression ◽  
Hcc Cells

Abstract Background: Forkhead box C1 (FOXC1), as a member of the FOX family, is important for promote HCC invasion and metastasis. FOX family protein lays a pivotal role in metabolism. ROS is involved in tumor progression and is associated with the expression of lots of transcription factors. We next explored the mechanism underlying FOXC1 modulating the metabolism and ROS hemostasis in HCC.Methods: We used amino acids arrays to verify which metabolism is involved in FOXC1-induced HCC. The kits were used to detect the ROS levels in HCC cells with over-expression or down-expression of FOXC1. After identified the downstream target genes and candidate pathway which regulated by FOXC1 during HCC progression in vitro and in vivo, we used western blot, immunohistochemistry, bisulfite genomic sequencing, methylation-specific PCR, chromatin immunoprecipitation analysis and luciferase reporter assays to explore the relationship of FOXC1 and downstream genes. Moreover, the correlation between FOXC1 and target genes and the correlation between target genes and the recurrence and overall survival were analyzed in two independent human HCC cohorts.Results: Here, we reported that FOXC1 could inhibit the cysteine metabolism and increase reactive oxygen species (ROS) levels by regulating cysteine metabolism-related genes, cystathionine γ-lyase (CTH). Overexpression of CTH significantly suppressed FOXC1-induced HCC proliferation, invasion and metastasis, while the reduction in cell proliferation, invasion and metastasis caused by the inhibition of FOXC1 could be reversed by knockdown of CTH. Meanwhile, FOXC1 upregulated de novo DNA methylase 3B (DNMT3B) expression to induce DNA hypermethylation of CTH promoter, which resulted in low expression of CTH in HCC cells. Moreover, low levels of ROS induced by N-acetylcysteine (NAC) which is an antioxidant inhibited the cell proliferation, migration, and invasion abilities mediated by FOXC1 overexpression, whereas high levels of ROS induced by L-Buthionine-sulfoximine (BSO) rescued the suppression results mediated by FOXC1 knockdown. Our study demonstrated that the overexpression of FOXC1 that was induced by the ROS dependent on the extracellular regulated protein kinases 1 and 2 (ERK1/2)- phospho-ETS Transcription Factor 1 (p-ELK1) pathway. In human HCC tissues, FOXC1 expression was positively correlated with oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG), p-ELK1 and DNMT3B expression, but negatively correlated with CTH expression. HCC patients with positive co-expression of 8-OHdG/FOXC1 or p-ELK1/FOXC1 or FOXC1/DNMT3B had the worst prognosis, whereas HCC patients who had positive FOXC1 and negative CTH expression exhibited the worst prognosis. Conclusion: In a word, we clarify that the positive feedback loop of ROS-FOXC1-cysteine metabolism-ROS is important for promoting liver cancer proliferation and metastasis, and this pathway may provide a prospective clinical treatment approach for HCC.

TUG1 as ceRNA combined with miR-29a to promotes the expression of IFITM3 in hepatocellular carcinoma

2020 ◽  
Author(s):  
Weiwei Liu ◽  
Qian Feng ◽  
Wenjun Liao ◽  
Jun Gao ◽  
Jiyuan Ai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Regulatory Relationship ◽  
Liver Cancer Cells ◽  
Tumor Tissues ◽  
Important Relationship ◽  
Hcc Cells

Abstract Background: Numerous studies have shown that TUG1 has an important relationship with tumorigenesis. TUG1 is highly expressed in most tumors and can promote tumor development. However, the role of TUG1 in hepatocellular carcinoma (HCC) remains to be studied. miR-29a plays a tumor suppressor role in a variety of tumors, and there is a relationship between TUG1 and miR-29a, but the specific relationship and mechanism of action are still unclear. miR-29a can inhibit the expression of IFITM3. However, the regulatory relationship between these three components requires elucidation. This study aimed to investigate the regulatory relationship between TUG1, miR-29a, and IFITM3 in human hepatocarcinogenesis.Methods: The expression levels of TUG1 and miR-29a in tumor tissues and adjacent non-tumor tissues of 41 HCC patients were detected by real-time quantitative polymerase chain reaction. The migration and invasion of liver cancer cells were studied by a wound healing assay and the Transwell method. The apoptosis rate of hepatocarcinoma cells was detected by flow cytometry, and the proliferation rate of hepatoma cells was detected by the EdU method. Immunofluorescence was selected to detect the expression of TUG1 and IFITM3 in HCC-LM3 and HL-7702. The relationship between TUG1 and miR-29a was detected using a double luciferase report and FISH. Tumors were established in vivo by subcutaneous injection of hepatocellular carcinoma cells into nude mice and injection of these cells into the tail vein. Western blotting was used to quantify the biomarkers. Results: TUG1 expression increased significantly in both tumor tissues and HCC cells. The expression of miR-29a in liver cancer tissues was also significantly lower than that in normal human liver tissues. The expression of TUG1 in HCC tissue samples was negatively correlated with that of miR-29a. Moreover, the expression of TUG1 was positively correlated with the expression of IFITM3. TUG1 can regulate the migration, invasion, apoptosis, and proliferation of HCC lines in vitro and regulate the development of tumors in vivo. Knocking down TUG1 will increase miR-29a expression, and thus, weaken the invasion, migration, and proliferation of HCC cells and enhance their apoptosis. miR-29a can affect the occurrence and progression of liver cancer through IFITM3. It was found that TUG1 regulates IFITM3 in HCC cells via miR-29a, and its expression affects cell invasion, migration, proliferation, and apoptosis.Conclusion: As a CeRNA, TUG1 competitively binds 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, and TUG1 is expected to serve as a key gene to improve the prognosis of patients.

CLTRN, regulated by NRF1/RAN/DLD protein complex, enhances radiation sensitivity of hepatocellular carcinoma cells through ferroptosis pathway

2020 ◽  
Author(s):  
Yin Yuan ◽  
Wen Cao ◽  
Hongbing Zhou ◽  
Haixin Qian ◽  
Honggang Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factor ◽  
Radiation Sensitivity ◽  
Migration And Invasion ◽  
Glutathione Metabolism ◽  
Rna Seq ◽  
X Ray ◽  
Hcc Cells

Abstract Background Radiotherapy is a viable treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, radiation resistance is an issue that needs to be addressed. In this context, cumulative evidence supports the functional roles of a variety of RNA or proteins in radioresistance, and suggests that the modulation of their expression may constitute a novel radiosensitization approach. Here, we investigated the ability of collectrin (CLTRN) to enhance the radiosensitivity in HCC patients for the first time. Methods Transcriptome sequencing technology (RNA-seq technology) was used to analyze the transcription-level changes in the genes from the HepG2 cells before and after X-ray irradiation. Combining the results with the HCC tissue RNA-seq data, we determined the ultimate target gene through bioinformatics analysis and cellular verification. A series of cellular and molecular biology techniques were applied in vitro and in vivo to confirm whether CLTRN can enhance radiosensitivity in HCC cells. Subsequently, the downstream action mechanism, the upstream transcription factor, and the interaction proteins of CLTRN were determined. Results First, we confirmed the association between CLTRN and radiosensitivity. We observed that CLTRN overexpression led to a significant reduction in the proliferation, migration, and invasion potential of X-ray-irradiated HCC cells, whereas no observable effect was exerted on cell cycle and apoptosis. The same results were observed in nude mice in vivo. Investigation of the gene regulatory mechanism revealed that the genes analyzed at transcriptome level after CLTRN overexpression were mostly enriched in the glutathione metabolic pathway. As glutathione metabolism forms a vital link in ferroptosis, we surmised that CLTRN is associated with ferroptosis. This was confirmed through the detection of cellular iron, ROS level determination, transmission electron microscopy, and monitoring of ferroptosis-related protein indicators. Lastly, we investigated whether nuclear respiratory factor 1 (NRF1) is the upstream transcription factor of CLTRN, and whether dihydrolipoamide dehydrogenase (DLD) and members of the RAS oncogene family (RAN) are its interacting proteins. Conclusion Our results indicate that CLTRN is a vital regulator of radiation sensitivity and could serve as a novel therapeutic target or prognostic marker in HCC treatment.

scholarly journals FOXC1 promotes HCC proliferation and metastasis by Upregulating DNMT3B to induce DNA Hypermethylation of CTH promoter

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhuoying Lin ◽  
Wenjie Huang ◽  
Qin He ◽  
Dongxiao Li ◽  
Zhihui Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Target Genes ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Dna Hypermethylation ◽  
Cysteine Metabolism ◽  
Proliferation And Metastasis ◽  
Dnmt3b Expression ◽  
Hcc Cells

Abstract Background Forkhead box C1 (FOXC1), as a member of the FOX family, is important for promote HCC invasion and metastasis. FOX family protein lays a pivotal role in metabolism. ROS is involved in tumor progression and is associated with the expression of lots of transcription factors. We next explored the mechanism underlying FOXC1 modulating the metabolism and ROS hemostasis in HCC. Methods We used amino acids arrays to verify which metabolism is involved in FOXC1-induced HCC. The kits were used to detect the ROS levels in HCC cells with over-expression or down-expression of FOXC1. After identified the downstream target genes and candidate pathway which regulated by FOXC1 during HCC progression in vitro and in vivo, we used western blot, immunohistochemistry, bisulfite genomic sequencing, methylation-specific PCR, chromatin immunoprecipitation analysis and luciferase reporter assays to explore the relationship of FOXC1 and downstream genes. Moreover, the correlation between FOXC1 and target genes and the correlation between target genes and the recurrence and overall survival were analyzed in two independent human HCC cohorts. Results Here, we reported that FOXC1 could inhibit the cysteine metabolism and increase reactive oxygen species (ROS) levels by regulating cysteine metabolism-related genes, cystathionine γ-lyase (CTH). Overexpression of CTH significantly suppressed FOXC1-induced HCC proliferation, invasion and metastasis, while the reduction in cell proliferation, invasion and metastasis caused by the inhibition of FOXC1 could be reversed by knockdown of CTH. Meanwhile, FOXC1 upregulated de novo DNA methylase 3B (DNMT3B) expression to induce DNA hypermethylation of CTH promoter, which resulted in low expression of CTH in HCC cells. Moreover, low levels of ROS induced by N-acetylcysteine (NAC) which is an antioxidant inhibited the cell proliferation, migration, and invasion abilities mediated by FOXC1 overexpression, whereas high levels of ROS induced by L-Buthionine-sulfoximine (BSO) rescued the suppression results mediated by FOXC1 knockdown. Our study demonstrated that the overexpression of FOXC1 that was induced by the ROS dependent on the extracellular regulated protein kinases 1 and 2 (ERK1/2)- phospho-ETS Transcription Factor 1 (p-ELK1) pathway. In human HCC tissues, FOXC1 expression was positively correlated with oxidative damage marker 8-hydroxy-2′-deoxyguanosine (8-OHdG), p-ELK1 and DNMT3B expression, but negatively correlated with CTH expression. HCC patients with positive co-expression of 8-OHdG/FOXC1 or p-ELK1/FOXC1 or FOXC1/DNMT3B had the worst prognosis, whereas HCC patients who had positive FOXC1 and negative CTH expression exhibited the worst prognosis. Conclusion In a word, we clarify that the positive feedback loop of ROS-FOXC1-cysteine metabolism-ROS is important for promoting liver cancer proliferation and metastasis, and this pathway may provide a prospective clinical treatment approach for HCC.

scholarly journals LncRNA DLGAP1-AS2 SiRNA Silencing Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Up-regulating MiR-154-5p Through Methylation

2020 ◽  
Author(s):  
Kai Chen ◽  
Zhuqing Zhang ◽  
Aijun Yu ◽  
Jian Li ◽  
Jinlong Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Migration ◽  
Migration And Invasion ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
Specific Pcr ◽  
Tumor Tissues ◽  
Sirna Silencing ◽  
And Migration ◽  
Hcc Cells

Abstract Background:DLGAP1-AS2 has been characterized as an oncogenic lncRNA in glioma. This study was performed to explore the role of DLGAP1-AS2 in hepatocellular carcinoma (HCC). Methods:Expression of DLGAP1-AS2 and miR-154-5p in paired HCC and non-tumor tissues from 62 HCC patients was determined by RT-qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1-AS2 for HCC. DLGAP1-AS2 siRNA silencing and miR-154-5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR-154-5p was analyzed by methylation-specific PCR. Cell proliferation was analyzed by CCK-8 assay.Results: DLGAP1-AS2 was upregulated in HCC and predicted poor survival. MiR-154-5p was downregulated in HCC and inversely correlated with DLGAP1-AS2. In HCC cells, DLGAP1-AS2 siRNA silencing resulted in the upregulation of miR-154-5p and decreased methylation of miR-154-5p gene. Transwell assay showed that, DLGAP1-AS2 siRNA silencing and miR-154-5p overexpression inhibited cell invasion and migration, and the combination of LGAP1-AS2 siRNA silencing and miR-154-5p overexpression showed stronger effects.Conclusion: DLGAP1-AS2 siRNA silencing may inhibit HCC cell migration and invasion by up-regulating miR-154-5p through methylation.

scholarly journals Long non-coding RNA linc-ITGB1 promotes cell proliferation, migration, and invasion in human hepatoma carcinoma by up-regulating ROCK1

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Lei Huang ◽  
Xinyu Li ◽  
Weijie Gao
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Serum Levels ◽  
Migration And Invasion ◽  
Healthy Controls ◽  
Human Hepatoma ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Long Non Coding Rna ◽  
Hcc Cells

Background: Linc-ITGB1 is a newly identified long non-coding RNA (lncRNA) involved in the regulation of cell migration and invasion of gallbladder cancer cell lines, while its involvement in human hepatoma carcinoma (HCC) is unknown. Methods: In the present study, HCC patient tumor tissues, adjacent healthy tissues and whole blood were collected from both HCC patients and healthy controls. Expression of LINC-ITGB1 was examined by qRT-PCR. Diagnostic value of serum LINC-ITGB1 for HCC was evaluated by receiver operating characteristic (ROC) curve analysis. Correlation between the serum LINC-ITGB1 and basic clinical information of patients was analyzed by chi-square test. LINC-ITGB1 overexpression HCC cell lines were established and the effects on cell proliferation, migration, and invasion were explored by CCK-8 assay and Transwell assay. Effects of LINC-ITGB1 overexpression on Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) expression were investigated by Western blot. Results: We found that LINC-ITGB1 was up-regulated in tumor tissues than in adjacent healthy tissues. Serum levels of LINC-ITGB1 were higher in HCC patients than in healthy controls. Serum levels of LINC-ITGB1 were significantly correlated with tumor size and distant tumor metastasis. LINC-ITGB1 overexpression promoted the proliferation, migration, and invasion of HCC cells and the expression of ROCK1. ROCK1 inhibitor reduced the effects of LINC-ITGB1 overexpression on cell proliferation, migration, and invasion. Conclusion: We conclude that lncRNA LINC-ITGB1 can promote the proliferation, migration, and invasion of HCC cells by up-regulating ROCK1.

scholarly journals 6-Phosphogluconolactonase Promotes Hepatocellular Carcinogenesis by Activating Pentose Phosphate Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Changzheng Li ◽  
Jie Chen ◽  
Yishan Li ◽  
Binghuo Wu ◽  
Zhitao Ye ◽  
...  
Keyword(s):  
Pentose Phosphate Pathway ◽  
Poor Prognosis ◽  
Pentose Phosphate ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Sequencing Data ◽  
Rapid Disease Progression ◽  
Cancer Genome Atlas ◽  
Proliferation And Metastasis ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) has a poor prognosis due to the rapid disease progression and early metastasis. The metabolism program determines the proliferation and metastasis of HCC; however, the metabolic approach to treat HCC remains uncovered. Here, by analyzing the liver cell single-cell sequencing data from HCC patients and healthy individuals, we found that 6-phosphogluconolactonase (PGLS), a cytosolic enzyme in the oxidative phase of the pentose phosphate pathway (PPP), expressing cells are associated with undifferentiated HCC subtypes. The Cancer Genome Atlas database showed that high PGLS expression was correlated with the poor prognosis in HCC patients. Knockdown or pharmaceutical inhibition of PGLS impaired the proliferation, migration, and invasion capacities of HCC cell lines, Hep3b and Huh7. Mechanistically, PGLS inhibition repressed the PPP, resulting in increased reactive oxygen species level that decreased proliferation and metastasis and increased apoptosis in HCC cells. Overall, our study showed that PGLS is a potential therapeutic target for HCC treatment through impacting the metabolic program in HCC cells.

scholarly journals LncRNA FGD5-AS1 functions as an oncogene to upregulate GTPBP4 expression by sponging miR-873-5p in hepatocellular carcinoma

2021 ◽  
Vol 65 (4) ◽  
Author(s):  
Nuobei Zhang ◽  
Hao Shen ◽  
Shenan Huang ◽  
Fenfen Wang ◽  
Huifang Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Downstream Target ◽  
Tumor Tissues ◽  
Induced Apoptosis ◽  
Hcc Cells

The long non-coding FGD5-AS1 (LncFGD5-AS1) has been reported to be a novel carcinogenic gene and participant in regulating tumor progression by sponging microRNAs (miRNAs). However, the pattern of expression and the biological role of FGD5-AS1 in hepatocellular carcinoma (HCC) remains largely unknown. The expression level of FGD5-AS1 in tumor tissues and cell lines was measured by RT-qPCR. CCK-8, EdU, flow cytometry, wound healing, and transwell chamber assays were performed to investigate the role of FGD5-AS1 in cell proliferation, apoptosis, migration, and invasion in HCC. Dual luciferase reporter, and RNA pull-down assays were performed to identify the regulatory interactions among FGD5-AS1, miR-873-5p and GTP-binding protein 4 (GTPBP4). We found that the expression of FGD5-AS1 was upregulated in HCC tissues and cell lines. Moreover, the knockdown of FGD5-AS1 suppressed cell proliferation, migration and invasion, and induced apoptosis in HCC cells. Further studies demonstrated that FGD5-AS1 could function as a competitive RNA by sponging miR-873-5p in HCC cells. Moreover, GTPBP4 was identified as direct downstream target of miR-873-5p in HCC cells and FGD5-AS1mediated the effects of GTPBP4 by competitively binding with miR-873-5p. Taken together, this study demonstrated the regulatory role of FGD5-AS1 in the progression of HCC and identified the miR-873-5p/GTPBP4 axis as the direct downstream pathway. It represents a promising novel therapeutic strategy for HCC patients.

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