WNT7A Overexpression Inhibits Growth and Migration of Hepatocellular Carcinoma via the β-Catenin Independent Pathway

Background/Aims. Hepatocellular carcinoma (HCC) is the lethal digestive cancer and the second leading cause of cancer death in men worldwide. Wnt7a, a 39Kd secreted glycoprotein composed of 349 amino acids, was reported to be related to various diseases. However, its role in HCC has not been studied yet. In this study, using gene expression data and clinical information obtained from the Oncomine and KMplot database, we acknowledged that WNT7A was underexpressed in HCC cancer tissue compared with normal tissue, and WNT7A underexpression was correlated with the decreased survival rate of HCC patients. The function of Wnt7a in cell viability, apoptosis, and migration was evaluated by biological behavior assay and molecular analysis. The findings revealed that WNT7A overexpression significantly restrained cell viability and migration while enhancing apoptosis. In addition, WNT7A overexpression promoted cell apoptosis by strengthening Caspase-3 activity and inhibited migration by downregulating EMT transcriptional factor Snail. Furthermore, the expression level of SKP2 was significantly downregulating in the WNT7A overexpression group. In conclusion, this study illustrated that overexpression of WNT7A inhibited cell viability and migration, which was likely attributed to the regulation of SKP2/P21.

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

BMC Infectious Diseases ◽

10.1186/s12879-020-05713-0 ◽

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.

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

10.21203/rs.2.17888/v3 ◽

2020 ◽

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.

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

10.21203/rs.2.17888/v2 ◽

2020 ◽

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.

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MicroRNA‐27a‐3p inhibits cell viability and migration through down‐regulating DUSP16 in hepatocellular carcinoma

Journal of Cellular Biochemistry ◽

10.1002/jcb.26526 ◽

2018 ◽

Vol 119 (7) ◽

pp. 5143-5152 ◽

Cited By ~ 12

Author(s):

Jin‐Mao Li ◽

Jun Zhou ◽

Zhen Xu ◽

Hai‐Jin Huang ◽

Min‐Jiang Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Viability ◽

And Migration

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Zingiberensis Newsaponin Inhibits the Malignant Progression of Hepatocellular Carcinoma via Suppressing Autophagy Moderated by the AKR1C1-Mediated JAK2/STAT3 Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/4055209 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Keqing He ◽

Xing Liu ◽

Shiping Cheng ◽

Pingsheng Zhou

Keyword(s):

Oxidative Stress ◽

Hepatocellular Carcinoma ◽

Protein Expression ◽

Cell Viability ◽

Underlying Mechanism ◽

Anticancer Effect ◽

Stat3 Pathway ◽

Stress Markers ◽

And Migration ◽

Hcc Cells

Objective. Saponins are a group of compounds from various plants, which exhibit an anticancer activity. This study aimed to explore the anticancer effect of zingiberensis newsaponin (ZnS) against hepatocellular carcinoma (HCC) and the underlying mechanism involving autophagy. Methods. HCC cells (Huh7 and SMMC7721) were treated with ZnS and/or 3-MA. The cell viability, migration, and apoptosis were determined using CCK-8 assay, transwell assay, and flow cytometry, respectively. The levels of oxidative stress markers (ROS, SOD, and MDA) were measured by ELISA assay. Autophagy was monitored using MDC assay, immunofluorescence staining, and transmission electron microscopy. The relative protein expression of LC3II/LC3I, P62, AKR1C1, p-JAK2, p-STAT3, JAK2, and STAT3 was determined using Western blot. Results. ZnS or 3-MA inhibited the cell viability and migration, and it promoted cell apoptosis and oxidative stress in HCC. MDC-positive cells and autophagosomes were reduced by ZnS or 3-MA treatment. The expression of autophagy-related proteins LC3 (LC3II/LC3I) and P62 was, respectively, downregulated and upregulated after ZnS or 3-MA treatment. In addition, ZnS or 3-MA suppressed the protein expression of AKR1C1, p-JAK2, and p-STAT3 in HCC cells. Furthermore, the above phenomena were evidently enhanced by ZnS combined 3-MA treatment. AKR1C1 overexpression weakened the effect of ZnS on inhibiting the expression of AKR1C1, p-JAK2, and p-STAT3. Conclusion. ZnS exerts an anticancer effect on HCC via inhibiting autophagy moderated by the AKR1C1-mediated JAK2/STAT3 pathway. ZnS and 3-MA exert a synergistic effect on inhibiting HCC.

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Role of ADP Ribosylation Factor Guanylate Kinase 1 in the Malignant Biological Behavior of Gastric Cancer

10.21203/rs.3.rs-699733/v1 ◽

2021 ◽

Author(s):

Qiong Luo ◽

Suyun Zhang ◽

Fan Yang ◽

Rui Feng ◽

Qian Xu ◽

...

Keyword(s):

Gastric Cancer ◽

Nude Mice ◽

Caspase 3 ◽

Cell Counting ◽

Biological Behavior ◽

Guanylate Kinase ◽

Invasion And Migration ◽

Adp Ribosylation ◽

And Migration ◽

Adp Ribosylation Factor

Abstract Objectives: To study the effects of ADP ribosylation factor guanylate kinase 1 gene (ASAP1) on the biological behavior of malignant gastric cancer (GC), and explore its possible molecular mechanisms in tumorigenesis and tumor progression.Methods: Quantitative PCR and western blotting (WB) were performed to measure ASAP1 mRNA and protein expression in the GES-1 epithelial cell line, which is derived from normal human mucosa, and three GC cell lines. Molecular biology techniques such as lentivirus packaging, infection, and screening were used to obtain BGC823 GC cells overexpressing ASAP1 and BGC823 and MKN45 cells with ASAP1 knocked down. The Cell Counting Kit-8 assay, colony formation assay, flow cytometry using Annexin V/propidium iodide, Transwell migration and invasion assays, and scratch assay were used to assess the malignant biological behavior of GC cells with ASAP1 overexpression and knockdown. WB was conducted to evaluate the effects of ASAP1 expression on angiogenesis, as well as on the expression of matrix metalloproteinases (MMPs), apoptotic proteins, and epithelial-mesenchymal transition (EMT)-related proteins. Nude mice bearing transplanted tumors were evaluated to determine the effect of ASAP1 knockdown on BGC823 GC cells.Results: ASAP1 expression in GC cells was greater than that in GES-1 normal gastric mucosal epithelial cells. ASAP1 overexpression significantly enhanced the proliferation, invasion, and migration of GC cells and reduced apoptosis; whereas ASAP1 knockdown significantly reduced the proliferation, invasion, and migration of GC cells and promoted apoptosis. In the ASAP1-knockdown group, expression of cleaved-caspase 3, cleaved-poly-ADP-ribose polymerase (PARP), and the epithelial marker E-cadherin increased significantly, whereas the expression of MMP2, MMP9, vascular endothelial growth factor A (VEGFA), and the mesenchymal markers N-cadherin, and vimentin decreased significantly (P<0.01). Knockdown of ASAP1 inhibited the growth of subcutaneously implanted tumors in nude mice.Conclusions: ASAP1 overexpression strongly promotes—whereas knockdown of ASAP1 effectively weakens—the malignant biological behavior of GC cells, possibly by reducing VEGFA expression and thus reducing angiogenesis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP, and reducing the activity of MMPs and EMT.

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The Diagnostic Efficacy and Biological Effects of microRNA-29b for Colon Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533034615604797 ◽

2016 ◽

Vol 15 (6) ◽

pp. 772-779 ◽

Cited By ~ 12

Author(s):

Leping Li ◽

Ying Guo ◽

Yuezhi Chen ◽

Jinshen Wang ◽

Lei Zhen ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Viability ◽

Early Stage ◽

Biological Effects ◽

Characteristic Curve ◽

Potential Effect ◽

Cancer Tissue ◽

Diagnostic Efficacy ◽

Incidence And Mortality ◽

And Migration

Background: Colorectal cancer is one of the most common cancers worldwide in terms of both incidence and mortality. The associations of expressions of tissue and plasma miR-29b were not detected in this study. Methods: There are 400 healthy age- and gender-matched controls enrolled in this study in a rate of 1:2. The receiver operating characteristic curve analysis was undertaken using the expression level for miR-29b in the colorectal cancer specimens from patients with cancer and healthy controls to assess the diagnostic accuracy of both tissue and plasma miR-29b levels. Results: It was found that the expression of plasma miR-29b is associated with the tissue miR-29b. Advanced study showed that aberrant miR-29b expression in both cancer tissues and plasma is associated with the clinicopathological data of patients with colorectal cancer. Tissue miR-29b showed an AUC of 0.883, with a sensitivity of 81.6% and a specificity of 84.9%. However, the AUC for plasma miR-29b was 0.743, with a sensitivity of 61.4% and a specificity of 72.5%. The analyses of the biological effects of miR-29b for colorectal cancer showed that miR-29b could inhibit the cell viability and migration. Conclusion: In summary, our data suggest that both the tissue and the plasma miR-29b levels have some value as a diagnostic tool for colorectal cancer. Advanced biological effects were conducted to detect the potential effect on the cell viability and migration. Future investigations including larger patient populations and patients with early-stage colorectal cancer are needed to confirm the potential diagnostic value of miRNA-29b in colorectal cancer.

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

10.21203/rs.2.17888/v1 ◽

2019 ◽

Author(s):

Ruoyu Wang ◽

Dong Zhang ◽

Kewei Sun ◽

Jianping Peng ◽

Wenfang Zhu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

T Cells ◽

T Cell ◽

Cell Viability ◽

Invasion And Migration ◽

Protein Levels ◽

Ifn Γ ◽

And Migration ◽

Cellular Immune

Abstract Purpose 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, and JAK2 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.

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Circ_0000190 favors gastric cancer patients potentially via inhibiting miR-1252/PAK3 pathway

10.21203/rs.3.rs-29489/v1 ◽

2020 ◽

Author(s):

Gui Jun Wang ◽

Tian Yu Yu ◽

Yan Rong Li ◽

Yang Jun Liu ◽

Bei-Bei Deng

Keyword(s):

Gastric Cancer ◽

Cell Viability ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Luciferase Reporter ◽

Circular Rnas ◽

Cancer Tissue ◽

Human Gastric Cancer ◽

Rt Pcr ◽

And Migration

Abstract Background Gastric cancer accounts for 8.3% of all cancer death and is demonstrated associated with aberrant circular RNAs (circRNAs) expressions.Circ_0000190 has been noted with prognostic role in gastric cancer. We aim to investigate the role and the underlying mechanism of circ_0000190 in gastric cancer.Methods Circ_0000190 expressions were examined in gastric cancer and adjacent normal tissues by RT-PCR. With gastric cancer cell lines, circ_0000190 expression was detected by FISH and RT-PCR. After forced expression, the role of the circRNA in gastric cancer cell viability, apoptosis, proliferation, cell cycle and migration was observed. The potential effector of circ_0000190 was predicted by computational screen and validated by luciferase reporter assay. The association of the effectors with circ_0000190’s effects above mentioned were examined. Mice model of human gastric cancer was established to observe the underlying mechanisms of circ_0000190.Results Circ_0000190 was down-regulated in gastric cancer tissue and cells, with a major location in cytoplasm. After transfection, circ_0000190 inhibited gastric cancer cell viability, proliferation and migration, and induced apoptosis and cycle, which was correlated with increased capase-3 and p27 expression, and decreased cyclinD expression. The circRNA was validated as a sponge of miR-1252, which directly targeted PAK3. The effects by circ_0000190 on the cellular processes above mentioned were blocked by miR-1252 mimics, and this was rescued after further overexpression of PAK3.Conclusions Our results revealed that circ_0000190 protected against gastric cancer, and this was via directly targeting miR-767-5p/PAK3 axis. Therefore, employing circ_0000190 might be a promising therapeutic strategy for treatment of gastric cancer.

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