scholarly journals Combined Chibby and β-Catenin Predicts Clinical Outcomes in Patients with Hepatocellular Carcinoma

2020 ◽  
Vol 21 (6) ◽  
pp. 2060
Author(s):  
Ming-Chao Tsai ◽  
Chao-Cheng Huang ◽  
Yu-Ching Wei ◽  
Ting-Ting Liu ◽  
Ming-Tsung Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Genetic Manipulation ◽  
Expression Patterns ◽  
D1 Protein ◽  
Disease Free Survival ◽  
Clinicopathological Parameters ◽  
Advanced Tumor ◽  
Low Expression

Chibby is an antagonist of β-catenin and is considered a potential tumor suppressor protein, but the role of Chibby in hepatocellular carcinoma (HCC) has not been characterized. The expression patterns of Chibby and β-catenin in HCC specimens and paired adjacent noncancerous tissues were measured by Western blotting and immunohistochemistry. The correlations between Chibby expression and clinicopathological parameters were analyzed. Then the biological functions of Chibby were analyzed in vitro. The Chibby protein was significantly downexpressed in human primary HCC tissues compared to that in matched adjacent normal liver tissue and is a risk factor for HCC recurrence and shorter survival. Furthermore, we found that in HCC tissues the high expression of β-catenin with low expression of Chibby in the nuclei was an independent predictor for disease-free survival (DFS) (p = 0.012) and overall survival (OS) (p = 0.005). Subsequent genetic manipulation in vitro studies revealed that Chibby knockdown induced the expression of β-catenin and C-myc, cyclin D1 protein, which promoted cell proliferation and invasiveness. In contrast, overexpression of Chibby decreased β-catenin expression and inhibited the cell proliferation and invasiveness. Our results suggest that low expression of Chibby was associated with advanced tumor-node-metastasis (TNM) stage and poor differentiation. Furthermore, the combination of Chibby and β-catenin can predict poor prognosis in patients with HCC. Chibby inhibited HCC progression by blocking β-catenin signaling in vitro. Chibby is a biomarker and may be a potential therapeutic target for HCC.

scholarly journals HOX Antisense lincRNA HOXA-AS2 Promotes Tumorigenesis of Hepatocellular Carcinoma

2016 ◽  
Vol 40 (1-2) ◽  
pp. 287-296 ◽  
Author(s):  
Fuqiang Wang ◽  
Huili Yang ◽  
Zhigang Deng ◽  
Yongjie Su ◽  
QinLiang Fang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Biological Function ◽  
Human Cancer ◽  
Rank Test ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Hcc Cells

Background: Recent studies reveal that long non-coding RNAs (LncRNAs) play critical roles in the proliferation and migration of human cancer. Previous report has shown that LncRNA HOXA-AS2 was involved in carcinoma processes. However, the expression and biological function of HOXA-AS2 in hepatocellular carcinoma (HCC) are poorly understood. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of HOXA-AS2 in HCC tissues and cell lines. The relation between lncRNA HOXA-AS2 expression and clinicopathological characteristics was assessed by chi-square test. The prognosis was analyzed using Kaplan-Meier method, and compared differences between the two groups by log-rank test. The biological function of HOXA-AS2 on HCC cells were determined both in vitro and in vivo. Results: In the present study, we found that HOXA-AS2 expression was increased in HCC tissues and adjacent normal tissues and high HOXA-AS2 expression was associated with bigger tumor size, advanced tumor stage, and shorter survival time. Knockdown of HOXA-AS2 significantly inhibited HCC cell proliferation and invasion and resulted in an increase of apoptosis. Furthermore, inhibition of HOXA-AS2 in HCC cells significantly repressed tumorigenicity in nude mice. Conclusion: Our results indicated that the inhibition of HOXA-AS2 in HCC cells significantly inhibited cell proliferation in vitro and in vivo, which might provide a potential possibility for targeted therapy of HCC.

scholarly journals The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 574
Author(s):  
Ming-Chao Tsai ◽  
Chih-Che Lin ◽  
Ding-Wei Chen ◽  
Yueh-Wei Liu ◽  
Yi-Ju Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Histological Grade ◽  
Significant Risk ◽  
Disease Free Survival ◽  
Tnm Stage ◽  
Clinicopathological Parameters ◽  
Advanced Tumor ◽  
Protease Activated Receptor 2

Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

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 Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transmembrane Domain ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Chi Square ◽  
Tumor Tissues ◽  
The Relationship ◽  
Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

scholarly journals Cyclin-Dependent Kinase Regulatory Subunit 2 Indicated Poor Prognosis and Facilitated Aggressive Phenotype of Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Jie Zhang ◽  
Qianqian Song ◽  
Jinxia Liu ◽  
Lina Lu ◽  
Yuqing Xu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Regulatory Subunit ◽  
Mrna Levels ◽  
Cyclin Dependent Kinase ◽  
Normal Tissues ◽  
Hcc Cells

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a member of the cell cycle-dependent protein kinase subunit family, which is implicated as an oncogene in various malignancies. However, the clinical significance, oncogenic functions, and related mechanisms of CKS2 in hepatocellular carcinoma (HCC) remain largely unclear. In the present study, expression features and prognostic value of CKS2 were evaluated in the bioinformatic databases and HCC tissues. The effects of CKS2 on the malignant phenotypes of HCC cells were explored in vitro. According to the analyses of three bioinformatic databases, mRNA levels of CKS2 were elevated in HCC tissues compared with the normal tissues. Immunohistochemical assays found that high CKS2 expression was closely associated with liver cirrhosis (P=0.019), poor differentiation (P=0.02), portal vein invasion (P<0.001), TNM stage (P=0.019), tumor metastasis (P=0.008), and recurrence (P=0.003). The multivariate regression analyses suggested that CKS2 was an independent prognostic factor for overall survival (HR=2.088, P=0.014) and disease-free survival (HR=2.511, P=0.002) of HCC patients. Moreover, the bioinformatic analyses indicated that CKS2 might be associated with the malignant phenotypes in HCC progression. In addition, in vitro assays showed that CKS2 expression was higher in HCC cell lines than in normal liver cells. Knockdown of CKS2 remarkably repressed the proliferation, colony formation (P=0.0003), chemoresistance, migration (P=0.0047), and invasion (P=0.0012) of HCC cells. Taken together, overexpression of CKS2 was significantly correlated with poor prognosis of HCC patients and the malignant phenotypes of HCC cells, suggesting that it was a novel prognostic biomarker and potential target of HCC.

miR-369-3p serves as prognostic factor and regulates cancer progression of hepatocellular carcinoma

2021 ◽  
Author(s):  
Can Chen ◽  
Yi Zong ◽  
Jiaojiao Tang ◽  
Ruisheng Ke ◽  
Lizhi Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Reverse Transcription Pcr ◽  
Huh7 Cells

Background: The aim of this study was to investigate the role of miR-369-3p in hepatocellular carcinoma (HCC). Materials & methods: The expression levels of miR-369-3p were detected using the quantitative real-time reverse transcription-PCR analysis. The cell counting kit-8 and transwell assays were used to explore the effects of miR-369-3p on cell proliferation, migration and invasion of HCC cells. Results: The miR-369-3p expression was downregulated in HCC tissues and cell lines, in comparison to the normal controls, respectively. In vitro, overexpression of miR-369-3p in Hep 3B and Huh7 cells inhibited cell proliferation, migration and invasion. SOX4 was a direct target of miR-369-3p. Conclusion: Our results suggested that miR-369-3p may be a tumor suppressor in HCC by targeting SOX4.

scholarly journals ACTN1 Supports Tumor Growth by Inhibiting Hippo Signaling in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Qian Chen ◽  
Xiao-Wei Zhou ◽  
Ai-Jun Zhang ◽  
Kang He
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Expression Pattern ◽  
Cytoskeletal Proteins ◽  
Gene Set Enrichment Analysis ◽  
Hippo Signaling ◽  
Hcc Cells

Abstract Background: Alpha actinins (ACTNs) are major cytoskeletal proteins and exhibit many non-muscle functions. Emerging evidence have uncovered the regulatory role of ACTNs in tumorigenesis, however, the expression pattern, biological functions, and underlying mechanism of ACTN1 in hepatocellular carcinoma (HCC) remain largely unexplored.Methods: Immunohistochemical analysis of a HCC tissue microarray (n = 157) was performed to determine the expression pattern and prognostic value of ACTN1 in HCC. In vitro loss-of-function study in HCC cells were carried out to investigate ACTN1 knockdown on cell proliferation. In vivo subcutaneous xenograft model and intrahepatic transplantation model were generated to decipher the contribution of ACTN1 in the tumor growth of HCC. Gene set enrichment analysis, quantitative real-time PCR, Co-immunoprecipitation, immunofluorescence and western blotting were performed to identify the underlying molecular mechanism.Results: It was found that ACTN1 was significantly upregulated in HCC tissues and closely related to llpha-fetoprotein level, tumor thrombus, tumor size, TNM stage and patient prognoses. Knockdown of ACTN1 suppressed in vitro cell proliferation and in vivo tumor growth of HCC cells. Mechanistically, knockdown of ACTN1 increased Hippo signaling pathway activity and decrease Rho GTPases activities. Mechanistically, ACTN1 could competitively interact with MOB1 and decrease the phosphorylation of LATS1 and YAP. The growth-promoting effect induced by ACTN1 was significantly abrogated by pharmacological inhibition of YAP with verteporfin or super-TDU.Conclusions: ACTN1 is highly expressed in HCC tissues and acts as a tumor promoter by suppressing Hippo signaling via physical interaction with MOB1. ACTN1 may serve as a potential prognostic marker and therapeutic target for HCC.

scholarly journals CTPS1 promotes malignant progression of triple-negative breast cancer with transcriptional activation by YBX1

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuxiang Lin ◽  
Jie Zhang ◽  
Yan Li ◽  
Wenhui Guo ◽  
Lili Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Triple Negative Breast Cancer ◽  
Transcriptional Activation ◽  
Triple Negative ◽  
Pearson Correlation ◽  
Disease Free Survival ◽  
Luciferase Reporter

Abstract Background Cytidine nucleotide triphosphate synthase 1 (CTPS1) is a CTP synthase which play critical roles in DNA synthesis. However, its biological regulation and mechanism in triple-negative breast cancer (TNBC) has not been reported yet. Methods The expression of CTPS1 in TNBC tissues was determined by GEO, TCGA databases and immunohistochemistry (IHC). The effect of CTPS1 on TNBC cell proliferation, migration, invasion, apoptosis and tumorigenesis were explored in vivo and in vitro. In addition, the transcription factor Y-box binding protein 1 (YBX1) was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. Pearson correlation analysis was utilized to assess the association between YBX1 and CTPS1 expression. Results CTPS1 expression was significantly upregulated in TNBC tissues and cell lines. Higher CTPS1 expression was correlated with a poorer disease-free survival (DFS) and overall survival (OS) in TNBC patients. Silencing of CTPS1 dramatically inhibited the proliferation, migration, invasion ability and induced apoptosis of MDA-MB-231 and HCC1937 cells. Xenograft tumor model also indicated that CTPS1 knockdown remarkably reduced tumor growth in mice. Mechanically, YBX1 could bind to the promoter of CTPS1 to promote its transcription. Furthermore, the expression of YBX1 was positively correlated with CTPS1 in TNBC tissues. Rescue experiments confirmed that the enhanced cell proliferation and invasion ability induced by YBX1 overexpression could be reversed by CTPS1 knockdown. Conclusion Our data demonstrate that YBX1/CTPS1 axis plays an important role in the progression of TNBC. CTPS1 might be a promising prognosis biomarker and potential therapeutic target for patients with triple-negative breast cancer.

scholarly journals LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yue Luo ◽  
Junhao Lin ◽  
Jiakang Zhang ◽  
Zhenghui Song ◽  
Dayong Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Rna Sequencing ◽  
Expression Pattern ◽  
Cell Lines ◽  
Disease Free Survival ◽  
Loss Of Function ◽  
Poor Overall Survival ◽  
Apoptotic Pathway ◽  
Qrt Pcr

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines. The effect of SNHG17 on proliferation, migration, and apoptosis of HCC was investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets, and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion, and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation and migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation, and apoptotic pathway; among them, 92 were overlapped with SNHG17-related genes in the TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2, and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival, and ERH and PDK4 also played a marked role in the prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.

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