scholarly journals Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5792
Author(s):  
Laura Francesca Pisani ◽  
Gian Eugenio Tontini ◽  
Carmine Gentile ◽  
Beatrice Marinoni ◽  
Isabella Teani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Expression Regulation ◽  
Gastric Epithelium ◽  
Cell Cycle Gene ◽  
Dependent Manner

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.

scholarly journals Pro-Inflammatory Interlekin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

2021 ◽  
Author(s):  
Laura Francesca Pisani ◽  
Gianeugenio Tontini ◽  
Carmine Gentile ◽  
Beatrice Marinoni ◽  
Isabella Teani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Gene Expression Regulation ◽  
Ex Vivo ◽  
Gastric Epithelium ◽  
Epithelial Cell Line ◽  
Cell Cycle Gene

Background: Interleukin (IL)-33 is a member of interleukin (IL)-1 family of cytokines which has been linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has direct effect on human gastric epithelial cells (GES-1) and on human gastric adenocarcinoma cell line (AGS) and gastric carcinoma cell line (NCI-N87), assessing its role in regulation of cell proliferation and cell cycle, apoptosis and necrosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Methods: cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assay, we also evaluated apoptosis by Caspase 3/8 Activity assay and Annexin V assays. Cell cycle were analyzed by means of Propidium Iodine assay and gene expression regulation was assessed by RT-PCR Profiling. Results: we found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell line, while it can stimulate proliferation and reduce apoptosis in normal epithelial cell line. These effects are also confirmed by the analysis of cell cycle gene expression which showed a reduced expression of proproliferative genes in cancer cells, in particular genes involved in G0/G1 and G2/M checkpoint. These results are confirmed by the gene expression analysis on surgical and bioptic specimens. Conclusions: the aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell type-dependent fashion.

Pro-Inflammatory Interlekin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

2020 ◽  
Author(s):  
Laura Francesca Pisani ◽  
Gianeugenio Tontini ◽  
Carmine Gentile ◽  
Beatrice Marinoni ◽  
Isabella Teani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Gastric Epithelium ◽  
Epithelial Cell Line ◽  
Cell Cycle Gene ◽  
Propidium Iodine ◽  
Apoptosis And Necrosis

Background: Interleukin (IL)-33 is a member of interleukin (IL)-1 family of cytokines which has been linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has direct effect on human gastric epithelial cells (GES-1) and on human gastric adenocarcinoma cell line (AGS), assessing its role in regulation of cell proliferation and cell cycle, apoptosis and necrosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Methods: cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assay, we also evaluated apoptosis and necrosis by Caspase 3/8 Activity assay and Propidium Iodine/Annexin V assays. Cell cycle were analyzed by means of Propidium Iodine assay and gene expression regulation was assessed by RT-PCR Profiling. Results: we found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell line, while it can stimulate proliferation and reduce apoptosis in normal epithelial cell line. These effects are also confirmed by the analysis of cell cycle gene expression which showed a reduced expression of proproliferative genes in AGS cells, in particular genes involved in G0/G1 and G2/M checkpoint. These results are confirmed by the gene expression analysis on surgical and bioptic specimens. Conclusions: the aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell type-dependent fashion.

Molecular and Functional Effects of the Novel MEK Inhibitor PD0325901 in Preclinical Models of Human Leukemias.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 254-254
Author(s):  
Michele Milella ◽  
Maria Rosaria Ricciardi ◽  
Chiara Gregorj ◽  
Fabiana De Cave ◽  
Steven L. Abrams ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Hematological Malignancies ◽  
Mek Inhibitor ◽  
Sensitive Cell ◽  
Fold Reduction

Abstract The Raf/MEK/ERK signaling module plays a pivotal role in the regulation of cell proliferation, survival, and differentiation. Our group, among others, has recently demonstrated that this pathway is frequently dysregulated in hematological malignancies and may constitute an attractive therapeutic target, particularly in AML. Here we investigated the effects of PD0325901, a novel MEK inhibitor, on phospho-protein expression, gene expression profiles, cell proliferation, and apoptosis in cell line models of AML, ALL, multiple myeloma (MM), ex vivo-cultured primary AML blasts, and oncogene-transformed hematopoietic cells. AML cell lines (OCI-AML2, OCI-AML3, HL-60) were strikingly sensitive to PD0325901 (IC50: 5–19 nM), NB4 (APL) and U266 (MM) showed intermediate sensitivity (IC50: 822 and 724 nM), while all the lymphoid cell lines tested and the myeloid cell lines U937 and KG1 were resistant (IC50 > 1000 nM). Cell growth inhibition was due to inhibition of cell cycle progression and induction of apoptosis. A statistically significant reduction in the proportion of S-phase cells (p=0.01) and increase in the percentage of apoptotic cells (p=0.019) was also observed in 18 primary AML samples in response to 100 nM PD0325901. Analysis of the correlation between sensitivity/resistance to PD0325901 and Ras/Raf mutation status is currently ongoing. PD0325901 effects were also examined in a panel of IL-3-dependent murine myeloid FDC-P1 cell lines transformed to grow in response to 11 different oncogenes in the absence of IL-3. Fms-, Ras-, Raf-1-, B-Raf-, MEK1-, IGF-1R-, and STAT5a-transformed FDC-P1 cells were very sensitive to PD0325901 (IC50: ~ 1 nM), while A-Raf-, BCR-ABL-, EGFR- or Src-transformed cells were 10 to 100 fold less sensitive (IC50: 10 to 100 nM); the parental, IL-3 dependent FDC-P1 cell line had an IC50 > 1000 nM. Analysis of the phosphorylation levels of 18 different target proteins after treatment with 10 nM PD0325901 showed a 5- to 8-fold reduction in ERK-1/2, observed only in sensitive cell lines, and a 2-fold reduction in JNK and STAT3 phosphorylation. PD0325901 (10 nM) treatment also profoundly altered the gene expression profile of the sensitive cell line OCI-AML3: 96 genes were modulated after 24 h (37 up- and 59 down-regulated), most of which involved in cell cycle regulation. Changes in cyclin D1 and D3, cyclin E, and cdc 25A were also validated at the protein level. Overall, PD0325901 shows potent growth-inhibitory and pro-apoptotic activity, indicating that MEK may be an appropriate therapeutic target in an array of different hematological malignancies. Further preclinical/clinical development of this compound is warranted, particularly in myeloid leukemias.

scholarly journals The Association of HOTAIR with the Diagnosis and Prognosis of Gastric Cancer and Its Effect on the Proliferation of Gastric Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Zhiying Xu ◽  
Hui Chen ◽  
Bin Yang ◽  
Xiangfeng Liu ◽  
Xiaoli Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Overall Survival ◽  
Cell Growth ◽  
Cell Lines ◽  
Roc Curve ◽  
Gastric Epithelium ◽  
Expression Levels ◽  
Qrt Pcr

Background. Long noncoding RNAs (lncRNAs) are a group of noncoding RNA with the length of more than 200nt. They have been identified as important diagnostic and prognostic molecules for many cancers and play an important role in the development of cancers. However, their clinical value and roles in gastric cancer (GC) remain unclear.Methods. The expression levels of HOTAIR in 54 GC tissues and their matched adjacent nontumor tissues from GC patients and 24 normal mucosa or those with minimal gastritis as healthy controls were determined by qRT-PCR. The expression levels of HOTAIR in human GC cell lines and a normal gastric epithelium cell line were also assessed by qRT-PCR. The potential relationships between its level in GC tissues and the clinicopathological features were analyzed. Furthermore, a receiver operating characteristic (ROC) curve was constructed. Additionally, the correlation between this lncRNA and overall survival (OS) was analyzed. SiRNA transfection was used to silence the expression of HOTAIR in GC cells. And cell proliferation and cell cycle assays were employed to determine the effect of HOTAIR on GC cell growth. Western blot was performed for the detection of the P53, P21, and Bcl2 proteins.Results. The expression levels of HOTAIR were significantly upregulated in GC tissues and cell lines. Increased HOTAIR was associated with tumor differentiation, lymph node and distant metastasis, and clinical stage. Furthermore, the area under the ROC curve (AUC) was up to 0.8416 (95 % CI=0.7661 to 0.9170, P<0.0001). The sensitivity and specificity were 66.67 and 87.04%, respectively. The correlation between HOTAIR expression and overall survival (OS) was statistically significant. The hazard ratio was 2.681, and 95% CI of ratio was 1.370 to 5.248. In addition, knockdown of HOTAIR can inhibit GC cell growth and affect cell cycle distribution. And knockdown of HOTAIR could enhance the protein levels of P21 and P53.Conclusion. The present study demonstrated that HOTAIR was highly expressed in GC tissues and may serve as a potential diagnostic and prognostic biomarker for GC. And HOTAIR promoted GC cell proliferation.

Effects of Uwhangchungsimwon on Cell Viability, Proliferation, and Gene Expression of Human Neuronal Cell line IMR32

2001 ◽  
Vol 29 (03n04) ◽  
pp. 445-458 ◽  
Author(s):  
Keun Song ◽  
Young-Suk Kim ◽  
Sang-Kwan Moon ◽  
Chang-Nam Ko ◽  
Ki-Ho Cho ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cell Line ◽  
Flow Cytometric Analysis ◽  
Neuronal Cell ◽  
Human Neuroblastoma Cell ◽  
Dependent Manner ◽  
Human Neuroblastoma

Uwhangchungsimwon (pill, UC) is one of the traditional Korean medical prescription that has been most frequently used for stroke. To Characterize the effects of UC on human neuronal cells, the human neuroblastoma cell line IMR32 was treated with UC, and cell viability, cell proliferation, apoptosis, and gene expression were analyzed. The effect of UC on recovery of cell viability was analyzed following stress induction by nutrient depletion or cold shock. Flow cytometric analysis of the cell cycle showed that UC inhibits cell cycle progression of IMR32 in a dose- and time-dependent manner. UC was also identified to increase cell viability and suppress apoptosis induction by a DNA-damaging agent, etoposide. Quantitative RT-PCR analysis revealed that expressions of the p53 tumor suppressor gene and its downstream effect, Waf1, are stimulated whereas expressions of positive cell cycle regulators, c-Myc, c-Fos, and Cyclin D1 were repressed by UC treatment. Moreover, while expression levels of apoptosis inhibitors, Bcl-2 and Bcl-XL were icreased following UC treatment, that of an apoptosis promoter, Bax, was decreased. In addition, expression of BMP-7, which has been recently demonstrated to improve the motor neuron recovery from stroke, was induced by UC while it was not detected in untreated cells. Taken together, our data suggest that the pharmacoclinical effects of UC might be derived in part from its negative regulation of cell proliferation and apoptosis through the transcriptional control of related genes.

scholarly journals Antileukemic Cell Proliferation of Active Compounds from Kaffir Lime (Citrus hystrix) Leaves

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1300 ◽  
Author(s):  
Songyot Anuchapreeda ◽  
Fah Chueahongthong ◽  
Natsima Viriyaadhammaa ◽  
Pawaret Panyajai ◽  
Riki Anzawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Wilms Tumor ◽  
Leukemic Cell ◽  
Dependent Manner ◽  
Wt1 Gene ◽  
Active Compounds ◽  
Trypan Blue Exclusion Method ◽  
Wt1 Protein

Kaffir lime (Citrus hystrix) is a plant member of family Rutaceae, and its leaves are commonly used in folk medicine. The present study explores antileukemic effects of the extracts and purified active compounds from the leaves. The antileukemic activity was investigated via inhibition of Wilms’ tumor 1 (WT1), which is a protein that involves in leukemic cell proliferation. In addition, the compounds were investigated for their effects on WT1 gene expression using real time RT-PCR and Western blotting. Cell cycle arrest and total cell number were investigated using flow cytometry and trypan blue exclusion method, respectively. The results demonstrated that the hexane fractionated extract had the greatest inhibitory effect on WT1 gene expression of many leukemic cell lines and significantly decreased WT1 protein levels of K562 cells (representative of the leukemic cells), in a dose- and time-dependent manner. Subfraction No. 9 (F9) after partial purification of hexane fractioned extract showed the highest suppression on WT1 protein and suppressed cell cycle at G2/M. The organic compounds were isolated from F9 and identified as phytol and lupeol. The bioassays confirmed antiproliferative activities of natural products phytol and lupeol. The results demonstrated anticancer activity of the isolated phytol and lupeol to decrease leukemic cell proliferation.

scholarly journals A Novel Gene RNF138 Expressed in Human Gliomas and Its Function in the Glioma Cell Line U251

2012 ◽  
Vol 35 (3) ◽  
pp. 167-178 ◽  
Author(s):  
You-xin Zhou ◽  
San-song Chen ◽  
Ting-feng Wu ◽  
Da-dong Ding ◽  
Xiong-hui Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Line ◽  
Brain Tissue ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Glioma Cell ◽  
Glioma Cell Line ◽  
Glioma Tissue ◽  
Glioma Cell Lines

Background: The gliomas represent the most common primary malignant brain tumors; however, little is known about the molecular pathogenesis of these tumors. Recent research reveals that the oncogenesis and development of gliomas have a close relation to the overexpression of several oncogenes and the inactivation of tumor suppressor genes. Whether the RING finger protein, RNF138, a newly discovered protein, plays a role in glioma oncogenesis is unknown. The present study investigates the expression levels of RNF138 mRNA in glioma samples and noncancerous brain samples and its function in the human glioma cell line U251.Methods: RT-PCR was used to ascertain the expression of RNF138 mRNA in the glioma cell lines U251, SHG44, U87, A172, and U373. The RNF138 mRNA expression levels of 35 pathological confirmed glioma samples (Grade I – 4 cases, Grade II – 13 cases, Grade III – 11 cases, and Grade IV – 7 cases) and five noncancerous brain tissue samples were analyzed by real-time quantitative PCR. By RNA interference (RNAi) with the lentivirus vector system, the expression of RNF138 was inhibited in the human astrocytomas-glioblastoma multiforme cell line U251. The effects of RNF138-knockdown on cell proliferation were assessed by Cellomics, and cell cycle and cell apoptosis were assessed by FACS.Results: The RNF138 mRNA is expressed in the five glioma cell lines, and its expression level is significantly higher in glioma tissue than in noncancerous brain tissue. By down-regulation of RNF138 expression, U251 cell proliferation was inhibited and cell apoptosis increased. At the same time, S stage cells lessened and G2 stage cells increased.Conclusion: The RNF138 gene is highly expressed in glioma tissue and glioma cell lines. It plays an important role in glioma cell proliferation, apoptosis, and cell cycle.

CYC065, a Potent Derivative of Seliciclib Is Active In Multiple Myeloma In Preclinical Studies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2999-2999 ◽  
Author(s):  
Samantha Pozzi ◽  
Diana Cirstea ◽  
Loredana Santo ◽  
Doris M Nabikejje ◽  
Kishan Patel ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Multiple Myeloma ◽  
Cell Line ◽  
Board Of Directors ◽  
Cell Lines ◽  
Preliminary Data ◽  
Research Funding ◽  
Preclinical Studies ◽  
Dependent Manner ◽  
Advisory Committees

Abstract Abstract 2999 Multiple myeloma (MM) is a treatable but incurable hematological malignancy and novel targeted therapies are under investigation. MM is characterized by dysregulation of the cell cycle, consequent to the overexpression of cyclins and their related kinases, the cyclins dependent kinases (CDK), a group of Ser/Thr proteine kinases. CDKs represent a promising therapeutic target, and inhibitors have been developed for anticancer treatment. We have previously studied seliciclib in the context of MM. CYC065, a second generation CDK inhibitor is the more potent derivative of seliciclib. It is mainly active on CDK 2, 5 and 9, involved in progression of the cell cycle and protein transcription. It has already shown promising results in preclinical studies in breast cancer and acute leukemia. We tested CYC065 in in vitro experiments in MM. Our preliminary data in 7 MM cell lines showed cytotoxicity of CYC065, both in MM cell lines sensitive as well as resistant to conventional chemotherapy, with an IC50 ranging between 0.06 and 2μ M, at 24 and 48h. Tritiated thymidine uptake assay confirmed the antiproliferative effects of CYC065 in MM, and its ability to overcome the growth advantage conferred by co-culture with bone marrow stromal cells derived from MM patients, and cytokines like interleukin 6 (10ng/ml) and insulin like growth factor-1 (50ng/ml). The anti-proliferative effect was evident both at 24 and 48h, starting at concentrations as low as 0.015μ M. The AnnexinV/PI assay in the MM1.s cell line confirmed CYC065's ability to induce apoptosis in a time dependent manner starting at 9 hours of treatment, at a concentration of 0.125 μ M, inducing 82% of apoptosis after 48h of exposure. Cell cycle analysis in the same MM1.s cell line showed an increase of subG1 phase, starting at 9 hours of treatment, at 0.125 μ M of CYC065. Preliminary results of western blot analysis confirmed the apoptotic effect of CYC065 in the MM1s cell line, highlighted by the cleavage of caspase 3, 8, 9 and PARP. The compound was tested in primary CD138+ cells isolated from three refractory MM patients, confirming its efficacy at 0.125 μ M, both at 24 and 48h. Comparative analysis in PBMCs from normal donors, for the evaluation of the drug toxicity is ongoing and will be presented. In conclusion our preliminary data confirm the efficacy of CYC065 in MM cell lines and primary MM cells, at nanomolar concentrations. Ongoing mechanistic and in vivo studies will delineate its role in the now increasing spectrum of CDK inhibitors in MM and better define its potential for clinical development in MM. Disclosures: Green: Cyclacel: Employment. Anderson:Millennium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Scadden:Fate Therapeutics: Consultancy, Equity Ownership, Patents & Royalties. Raje:Celgene: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Acetylon: Research Funding.

The role of HNF4A in GATA4-deficiency phenotypes of hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 284-284
Author(s):  
Yu Bin Tan ◽  
Timothy Shuen ◽  
Han Chong Toh
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Correlation Analysis ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Transgenic Mouse ◽  
Cell Lines ◽  
Downstream Target ◽  
Cycle Arrest

284 Background: Hepatocellular carcinoma (HCC) is the 2nd leading global cause of cancer death. Recently, we have discovered previously undescribed deletion and germline mutation of GATA4 and showed that GATA4 is a key differentiation driver and metabolic regulator in HCC. However, as GATA4 is mostly deleted in HCC, targeting GATA4-downstream molecules is ideal. In this study, proof-of-concept experiments were conducted to show that introduction of HNF4A, which is a GATA4-regulated downstream target, could partially rescue the impaired phenotypes in GATA4-deficient HCC cell line. Methods: Correlation analysis using gene expression microarray of human HCC samples was conducted to identify the genes that are positively correlated with GATA4. A transgenic mouse model with a liver-specific conditional GATA4 knockout was designed to identify liver morphology and gene expression changes which are correlated with the loss of Gata4 in the mouse liver. CRISPR-mediated knockout of GATA4 and lentiviral HNF4A overexpression was carried out in a GATA4-deficient HCC cell lines, PLC/PRF/5 and Hep3B, followed by proliferation, apoptosis, cell cycle and senescence functional assays. Results: Pearson correlation analysis from human HCC samples showed that expression of HNF4A is positively correlated with that of GATA4. Livers from conditional Gata4 knockout mice had lower Hnf4a gene expression when compared to age-matched control mice. Loss of function analysis by CRISPR-mediated GATA4 knockout further showed downregulation of HNF4A in GATA4-deficient PLC/PRF/5 cell line. Lentiviral HNF4A overexpression in PLC/PRF/5 and Hep3B demonstrated reduced proliferation and increased apoptosis while PLC/PRF/5 also showed cell cycle arrest at G2/M phase when compared to control. However, no senescence induction was detected in HNF4A-overexpressing cells. Conclusions: Transgenic mouse data, CRISPR-mediated knockout and analysis of HCC samples showed that HNF4A is a key GATA4-downstream target. HNF4A overexpression decreases proliferation, increases apoptosis and cell cycle arrest in GATA4-deficient HCC cell lines, thus representing a possible therapeutic target for HCC.

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