scholarly journals AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoling Liu ◽  
Chenyu Wang ◽  
Qing Yang ◽  
Yue Yuan ◽  
Yunjian Sheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Biological Function ◽  
Cell Metabolism ◽  
Hub Genes ◽  
Invasion And Migration ◽  
And Migration

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.

scholarly journals miR-206 inhibits cell proliferation, invasion, and migration by down-regulating PTP1B in hepatocellular carcinoma

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Qian Yang ◽  
Lunli Zhang ◽  
Yuanbin Zhong ◽  
Lingling Lai ◽  
Xiaopeng Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tyrosine Phosphatase ◽  
Tumor Development ◽  
Luciferase Reporter ◽  
Mice Model ◽  
Invasion And Migration ◽  
Huh7 Cells ◽  
And Migration

Abstract Protein tyrosine phosphatase 1B (PTP1B) has been reported as an oncogene in hepatocellular carcinoma (HCC). However, how PTP1B is regulated in HCC remains unclear. MicroRNAs (miRNAs) are a class of small non-coding RNAs involved many biological processes including tumorigenesis. In this study, we investigated whether miRNA participated in the regulation of PTP1B in HCC. We found that miR-206, which was down-regulated during tumorigenesis, inhibited HCC cell proliferation and invasion. Overexpression of miR-206 inhibited proliferation, invasion, and migration of HCC cell lines HepG2 and Huh7. Mechanistically, we demonstrated that miR-206 directly targeted PTP1B by binding to the 3′-UTR of PTP1B mRNA as demonstrated by the luciferase reporter assay. Overexpression miR-206 inhibited PTP1B expression while miR-206 inhibition enhanced PTP1B expression in HepG2 and Huh7 cells. Functionally, the regulatory effect on cell proliferation/migration/invasion of miR-206 was reversed by PTP1B overexpression. Furthermore, tumor inoculation nude mice model was used to explore the function of miR-206 in vivo. Our results showed that overexpression of miR-206 drastically inhibited tumor development. In summary, our data suggest that miR-206 inhibits HCC development by targeting PTP1B.

scholarly journals MiR-188-3p and miR-133b Suppress Cell Proliferation in Human Hepatocellular Carcinoma via Post-Transcriptional Suppression of NDRG1

2021 ◽  
Vol 20 ◽  
pp. 153303382110330
Author(s):  
Zhenzhao Luo ◽  
Yue Fan ◽  
Xianchang Liu ◽  
Shuiyi Liu ◽  
Xiaoyu Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Growth ◽  
Suppressive Effect ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
And Migration ◽  
Cancer Tissues ◽  
Suppress Cell Proliferation

Background: Previous studies reported that N-myc downstream-regulated gene 1 (NDRG1) was upregulated in various cancer tissues and decreased expression of miR-188-3p and miR-133b could suppress cell proliferation, metastasis, and invasion and induce apoptosis of cancer cells. However, the molecular mechanism of NRDG1 involved in hepatocellular carcinoma (HCC) tumorigenesis is still unknown. Methods: The expressions of miR-188-3p, miR-133b, and NRDG1 in HCC tissues and cells were quantified by qRT-PCR and Western blot. MTT assay and transwell invasion assay were performed to evaluate cell growth and cell migration, respectively. Luciferase reporter assay were performed to determine whether miR-188-3p and miR-133b could directly bind to NRDG1 in HCC cells. Results: The results showed that NRDG1 was upregulated and these 2 microRNAs were downregulated in HCC tissues. NRDG1 was negatively correlated with miR-188-3p and miR-133b in HCC tissues. MiR-188-3p and miR-133b were demonstrated to directly bind to 3′UTR of NRDG1 and inhibit its expression. Upregulation of miR-188-3p and miR-133b reduced NRDG1 expression in hepatocellular carcinoma cell lines, which consequently inhibited cell growth and cell migration. Conclusions: Our finding suggested that miR-188-3p and miR-133b exert a suppressive effect on hepatocellular carcinoma proliferation, invasion, and migration through downregulation of NDRG1.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

scholarly journals Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruoyu Wang ◽  
Dong Zhang ◽  
Kewei Sun ◽  
Jianping Peng ◽  
Wenfang Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cell Viability ◽  
Caspase 3 ◽  
Invasion And Migration ◽  
Ifn Γ ◽  
And Migration ◽  
Cellular Immune

Abstract Background Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. Methods The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. Results We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. Conclusion Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

miR-340 Inhibits the Development of Hepatocellular Carcinoma by Down-Regulating Akt Signaling Pathway

2021 ◽  
Vol 11 (9) ◽  
pp. 1785-1791
Author(s):  
Tangpeng Xu ◽  
Changli Ruan ◽  
Xu Bin ◽  
Mengxue Hu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Pathological Grade ◽  
Akt Signaling Pathway ◽  
Invasion And Migration ◽  
Proliferation Ability ◽  
And Migration ◽  
Cancer Tissues

Hepatocellular carcinoma (HCC) is a serious threat to human health. miR-340 participates in HCC pathogenesis, but its specific mechanism is not completely clear. Therefore, our study assessed the mechanism by how miR-340 involves in HCC. The cancer tissues and paracancerous tissues of HCC patients were collected. miR-340 mimics/NC and Akt siRNA were transfected into HepG2 cells followed by analysis of miR-304 and EMT-related molecules expression by Real-time PCR, cell invasion and migration by Transwell assay, cell proliferation ability by CCK8 assay as well as p-Akt and p-mTOR level by Western blot. miR-340 in HCC tissues was significantly downregulated compared to adjacent tissues (P <0.001). With increased pathological grade, miR-340 expression was decreased gradually. p-Akt and p-mTOR in HCC tissues was significantly upregulated and elevated gradually with increased pathological grade. p-Akt and p-mTOR was negatively associated with miR-340 (P <0.001). After overexpression of miR-340, HepG2 cell proliferation, invasion, migration and epithelialization were significantly inhibited, and p-Akt and p-mTOR was reduced. When Akt expression was interfered with siRNA, cell proliferation and epithelialization was further inhibited. miR-340 inhibits the development of hepatocellular carcinoma through Akt signaling pathway.

scholarly journals Long non-coding RNA LINC00152 regulates cell proliferation and migration by epigenetically repressing LRIG1 expression in cholangiocarcinoma

2020 ◽  
Author(s):  
Ni Wang ◽  
Yang Yu ◽  
Boming Xu ◽  
Chunmei Zhang ◽  
Jie Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Biological Function ◽  
Rna Seq ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Proliferation And Migration

Abstract Background: Recently, long non-coding RNAs (lncRNAs) have been verified to have significant regulatory roles in multiple human cancer processes. Long non-coding RNA LINC00152, located on chromosome 2p11.2, was identified as an oncogenic lncRNA in various cancers. However, the biological function and molecular mechanism of LINC00152 in cholangiocarcinoma (CCA) are still unknown.Methods: Bioinformatic analysis was performed to determine LINC00152 expression levels in the CCA and normal tissues by using raw microarray data downloaded from Gene Expression Omnibus (GSE76297) and The Cancer Genome Atlas (TCGA). Quantitative reverse transcription PCR (qRT-PCR) was used to validate LINC00152 expression in the CCA tissues compared with that in the paired normal tissues. CCK8, colony formation, Edu assays, transwell assays, flow cytometry, and in vivo tumor formation assays were performed to investigate the biological function of LINC00152 on CCA cell phenotypes. RNA-seq was carried out to identify the downstream target gene which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays were performed to reveal the factors involved in the mechanism of LINC00152 functions in CCA.Results: LINC00152 is significantly upregulated in cholangiocarcinoma. LINC00152 regulated the proliferation and migration of cholangiocarcinoma cells both in vitro and in vivo. RNA-seq revealed that LINC00152 knockdown preferentially affected genes linked with cell proliferation, cell differentiation and cell adhesion. Furthermore, mechanistic investigation validated that LINC00152 could bind EZH2 and modulate the histone methylation of promoter of leucine rich repeats and immunoglobulin like domains 1 (LRIG1), thereby affecting cholangiocarcinoma cells growth and migration.Conclusion: Taken together, these results demonstrated the significant roles of LINC00152 in cholangiocarcinoma and suggested a new diagnostic and therapeutic direction of cholangiocarcinoma.

scholarly journals MiR-18a-5p Promotes NPC Cell Proliferation, Invasion, Migration, and EMT by Targeting SMAD2

2020 ◽  
Author(s):  
Pengcheng Li ◽  
Junhui Xing ◽  
Jianwu Jiang ◽  
Xinyu Tian ◽  
Xuemeng Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Invasion And Migration ◽  
Metastasis Model ◽  
And Migration ◽  
Dual Luciferase Reporter Assay

Abstract Background: Nasopharyngeal carcinoma (NPC) is the most common malignant tumor in the head and neck that is characterized by high local malignant invasion and distant metastasis. miR-18a-5p reportedly plays an important role in tumorigenesis and development. However, little is known about the mechanism underlying miR-18a-5p’s role in NPC.Methods：Quantitative real-time PCR was used to detect the expression of miR-18a-5p in NPC tissues and cell lines. MTT assay and plate clone formation assay were used to detect the effect of miR-18a-5p on NPC cell proliferation. Woundhealing assays and Transwell assays were used to detect the effect of miR-18a-5p on NPC cell invasion and migration. The expressions of epithelialmesenchymal transition (EMT)-related proteins N-cadherin, Vimentin, and E-cadherin were detected by Westernblot. Bioinformatics and dual-luciferase reporter assay were used to detect the targeting interaction between miR-18a-5p and SMAD2. Xenotransplantation and metastasis model were used to detect the effect of miR-18a-5p on NPC growth and metastasis in vivo.Results:miR-18a-5p was highly expressed in NPC tissues and cell lines. Overexpression of miR-18a-5p promotedNPC cell proliferation, invasion, migration, and EMT process, whereas inhibition of miR-18a-5p expression led to the oppositeresults. Results of dual-luciferase reporter assay showed that SMAD2 was the target gene of miR-18a-5p, and SMAD2 could reverse the effect of miR-18a-5p on NPC cell line. Xenotransplantation and metastasis model experiments in nude mice showed that miR-18a-5p promotesNPC growth and metastasis in vivo.Conclusions:Targeting SMAD2 downregulated miR-18a-5p expression, thereby promoting NPC cell proliferation, invasion, migration, and EMT.

scholarly journals ATF2-Induced Overexpression of lncRNA LINC00882, as a Novel Therapeutic Target, Accelerates Hepatocellular Carcinoma Progression via Sponging miR-214-3p to Upregulate CENPM

2021 ◽  
Vol 11 ◽  
Author(s):  
Hua Ren ◽  
Zhi-cheng Wei ◽  
Yan-xia Sun ◽  
Chun-yan Qiu ◽  
Wen-jue Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Promoter Region ◽  
Tumor Xenograft ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Protein Coding ◽  
Invasion And Migration ◽  
And Migration ◽  
Hcc Cells

BackgroundLong intergenic non-protein coding RNA 882 (LINC00882) are abnormally expressed in several tumors. Our research aimed to uncover the functions and the potential mechanisms of LINC00882 in hepatocellular carcinoma (HCC) progression.MethodsRT-qPCR was applied to identify LINC00882 and miR-214-3p levels in HCC specimens and cells. Luciferase reporter was applied for the exploration of whether activating transcription factor 2 (ATF2) could bind to the promoter region of LINC00882. Cell proliferation, invasion, and migration were evaluated. In vivo tumor xenograft models were constructed to assess tumorigenicity. RT-PCR, Western blot and Luciferase reporter assays were conducted to examine the regulatory relationships among LINC00882, miR-214-3p and ATF2.ResultsLINC00882 was markedly upregulated in HCC cells and clinical specimens. Additionally, ATF2 could bind directly to the LINC00882 promoter region and activate its transcription. Loss-of-function studies further demonstrated that LINC00882 knockdown inhibited proliferation, invasion, and migration of HCC cells. Mechanistically, LINC00882 adsorbed miR-214-3p, thus promoting the expressions of CENPM. Rescue assays demonstrated that functions of LINC00882 deficiency in HCC cells were reversed through suppressing miR-214-3p.ConclusionOur group identified a novel regulatory axis of ATF2/LINC00882/miR-214-3p/CENPM, which may provide potential therapeutic targets for HCC.

scholarly journals MicroRNA-517c Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Downregulation of KPNA2 and Inhibition of PI3K/AKT Pathway

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Limin Ma ◽  
Changming Tao ◽  
Yingying Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Analysis ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
And Migration

Objective. Hepatocellular carcinoma (HCC) is a kind of solid and highly aggressive malignant tumor with poor prognosis. MicroRNA (miRNA/miR) has been confirmed to be involved in HCC development. The current study focused on the functions and mechanisms of miR-517c in HCC. Methods. Expressions of miR-517c and Karyopherin α2 (KPNA2) mRNA in HCC cell lines and tissue samples were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was conducted for detections of epithelial-to-mesenchymal transition (EMT) and PI3K/AKT markers. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell assays were utilized to investigate the influence of miR-517c on HCC cell proliferation, invasion, and migration. TargetScan and luciferase reporter assay were performed to search for the potential target gene of miR-517c. Results. We demonstrated that miR-517c expressions were decreased in HCC tissues and cells. Moreover, the clinical analysis showed that decreased miR-517c expressions in HCC tissues correlated with shorter overall survival and malignant clinicopathologic features of HCC patients. MTT assay showed that miR-517c upregulation prominently repressed HCC cell proliferation. In addition, miR-517c restoration could significantly suppress HCC cell invasion and migration as demonstrated by Transwell assays. We also found that miR-517c directly targeted KPNA2 and regulated the PI3K/AKT pathway and EMT, exerting prohibitory functions in HCC. Conclusion. Taken together, this study stated that miR-517c inhibited HCC progression via regulating the PI3K/AKT pathway and EMT and targeting KPNA2 in HCC, providing a novel insight into HCC treatment.

Sign in / Sign up

Export Citation Format

Share Document