Proliferation Of Liver Cancer Cells Research Articles

Transcriptomic and network pharmacology approaches revealed possible mechanisms underlying the 5-fluorouracil (5-FU)-sensitizing effect of Xuan-Fu-Hua decoction treatment on liver cancer cells.

BackgroundXuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action.MethodsThe impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches.ResultsXuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo. Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1, and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF, and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment.ConclusionsXuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery.

CircKIF5B Promotes Hepatocellular Carcinoma Progression by Regulating the miR-192 Family/XIAP Axis.

BackgroundThe long-term prognosis of HCC (hepatocellular carcinoma) with metastasis remains extremely poor. CircRNAs are promising as critical biological markers in identifying disease mechanisms and developing new effective treatments. However, the role of the aberrant expression of circRNAs in HCC progression remains largely unknown.MethodsCircKIF5B location was investigated by RNA fluorescence in situ hybridization (RNA-FISH). For circRNA determination, RNase R treatment and Real-Time Quantitative RT-PCR (qRT-PCR) were performed. Transwell chamber assays examined the chemotactic migration and invasion of liver cancer cells.ResultsThis study identified the circRNA circKIF5B originating from exons 1, 2, and 3 of the KIF5B gene. Importantly, we found that circKIF5B circRNA, rather than KIF5B linear mRNA, was notably upregulated in liver cancer cell lines and tissues. Moreover, we found that silencing circKIF5B markedly reduced the proliferation, invasion, and metastasis of liver cancer cells by sponging the miR-192 family, thus decreasing the expression of X-linked inhibitor of apoptosis (XIAP).ConclusionOur data demonstrate that circKIF5B can regulate XIAP expression by sponging miR-192 and miR-215 competing for the ceRNA mechanism, indicating that circKIF5B may act as an essential upstream regulator and providing mechanistic evidence to support the view that circKIF5B/miR-192s/XIAP is a promising therapeutic target for treating liver cancer.

Synergetic HepG2 cells suppression efficacy of Tripterygium wilfordii and Scutellaria barbata through EGFR/PI3K/Akt pathway

Traditional Chinese medicines (TCMs) Tripterygium wilfordii Hook. f. (TW) and Scutellaria barbata D. Don (SB) are reported to have anticancer activity. However, the synergetic anti-liver cancer efficacy is still unknown. Herein, we demonstrated that the combination of TW and fermentation product of SB by yeast (TW+SB) could markedly improve the HepG2 cell suppression capacity as compared to individual TW or SB. Hence, synergetic mechanisms of TW+SB combination were further investigated by systems pharmacology, LC-MS, etc. The results showed that fermentation increases the concentration of active components of SB rather than those of TW, leading to the increase of HepG2 cell inhibition efficacy of SB. TW+SB combination effectively suppresses proliferation, migration, and invasion of liver cancer cells by inducing EGFR/PI3K/Akt signaling pathway mediated apoptosis. In conclusion, TW+SB combination showed outstanding synergetic anti-liver cancer effect, and it might offer a promising treatment option for cancer patients.

New Insights Into the Persistent Effects of Acute Exposure to AFB1 on Rat Liver.

Aflatoxin B1 (AFB1) has mutagenesis, carcinogenesis and teratogenesis effects and mainly found in food crops and their processed foods. AFB1 exposure can cause acute or chronic liver poisoning, but there were few studies on the persistent effects of acute AFB1 exposure on the liver. In this study, rat liver injury models were established 2 and 7 days after single exposure to high and low doses of AFB1. The persistent effects of AFB1 single acute exposure (ASAE) on rat liver were analyzed from the phenotypic and genetic levels. The results showed that compared with the control group, liver function indexes, MDA content in liver and the number of apoptotic hepatocytes in model groups increased to the highest on the 2nd day after ASAE (p < 0.001). However, the changes of liver coefficient were most significant on the 7th day after ASAE (p < 0.01). The results of liver pathology showed that the liver injury was not alleviated and the activities of antioxidant enzymes GSH-Px and SOD were the lowest on the 7th day (p < 0.001). RNA-Seq results indicated that there were 236, 33, 679, and 78 significantly differentially expressed genes (DEGs) in the model groups (LA-2d, LA-7d, HA-2d, HA-7d) compared with the control group. Among them, the Gtse1 gene related to the proliferation, differentiation and metastasis of liver cancer cells, the Lama5 and Fabp4 gene related to the inflammatory response were significantly DEGs in the four model groups, and the differential expression of the immune system-related Bcl6 gene increased with the prolonged observation time after ASAE. In conclusion, ASAE can cause persistent liver damage in rats. The persistently affected genes Lama5, Gtse1, Fabp4, and Bcl6 possess the potential to be therapeutic targets for liver disease induced by AFB1.

Abstract 6295: Grape seed procyanidins inhibit cell proliferation &amp; induce apoptosis in both human breast &amp; liver cancer cell lines

Abstract As a potential anticancer agent, grape seed procyanidins (GSPs) have been shown to be effective in treating and preventing various cancer types, but the mechanistic inhibitory effect at cellular and molecular levels in most of the cancer types remains unclear. The objective of the present study was to investigate the potential influence of GSPs on both liver and breast cancers. The anticancer efficacy of GSPs was investigated in vitro, using two human cancer cell lines; human hepatocellular carcinoma (HepG2) and human breast carcinoma, Zr-75-1.The potential influence of extracted GSPs was examined on cell proliferation, clonogenic assays, morphological alteration, and western blot was used to analyze the expression of oncogenic signaling pathways of STAT3, β-catenin, T-ERK, and pERK, Bax, Bcl-2, mutant-p53, and caspase enzyme activity assay was measured by caspase colorimetric assay.Our data showed that GSPs treatment inhibits both cellular viability and proliferation in a concentration-and time-dependent fashion in both breast and liver cancer cell lines after 48h. Furthermore, mechanistic studies showed that GSPs induced late apoptosis by 72% that was associated with cell morphological changes, histone release from fragmented DNA, caspase-3 activation in a dose-dependent manner after 48h. Furthermore, GSPs down-regulated pERK, STAT3, β-catenin, and mutant p53 levels as well as increased p21and Bax, pro-apoptotic signal, in both breast and liver cancer cells as determined by western blot analysis. All in all, our findings suggest that GSPs inhibit breast and liver cancer cells proliferation and induce cell apoptosis by suppressing the oncogenic signaling pathways that play a role in cancer progression which in turn introduce GSPs as a promising phytochemical for cancer treatment. Citation Format: Rana Hamed Alneanaey, Nabil Taha, Mohammed Lebda, Aml Hashem, Ahmed Sultan. Grape seed procyanidins inhibit cell proliferation &amp; induce apoptosis in both human breast &amp; liver cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6295.

Abstract 4039: Cadmium modulates steatosis, fibrogenesis, and oncogenic signaling in hepatocellular carcinoma cells through activation of Notch/AKT/mTOR pathways

Abstract Cadmium (Cd) is an environmental pollutant that increases hepatotoxicity and the risk of liver diseases. In the current study, we investigated the effect of a physiologically relevant, low concentration of Cd on the regulation of liver cancer cell proliferation, steatosis, and fibrogenic/oncogenic signaling. Exposure of Cd (1 to 10 nM) increased endogenous reactive oxygen species (ROS) production and enhanced cell proliferation in non-tumor derived HepaRG liver cells and in hepatocellular carcinoma (HCC) cell lines. Exposure of Cd increased Jagged1 expression and activated Notch signaling in HepaRG and HCC cell lines. Cd activated AKT/mTOR signaling by increasing phosphorylation of AKT-S473 and mTOR-S-4448 residues. Moreover, a low concentration of Cd also promoted cell steatosis and induced fibrogenic signaling in HCC cells. Similarly chronic exposure of HCC cells to a low concentration of Cd activated Notch and AKT/mTOR signaling. Further RNA seq data revealed that chronic Cd exposure modulate cell steatosis/fibrogenic gene expression that involved in fatty liver disease development. Cd induced the expression of pro-inflammatory cytokines TNFα and its downstream oncogenic protein Tumor Necrosis Factor-alpha (TNF-α)-Induced Protein 8 (TNFAIP8). Collectively our data suggest that a low concentration of Cd modulates cell steatosis and fibrogenic/oncogenic signaling in HCC by activation of Notch/AKT/mTOR pathways. Citation Format: Suryakant Niture, Sashi Gadi, Minghui Lin, Qi Qi, John T. Moore, Deepak Kumar. Cadmium modulates steatosis, fibrogenesis, and oncogenic signaling in hepatocellular carcinoma cells through activation of Notch/AKT/mTOR pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4039.

The Role of Exosome MicroRNA-103 in the Proliferation and Invasion of Hepatoma Cells and Its Mechanism

Liver cancer (HCC) is a common malignant tumor whose incidence is increasing worldwide, but existing chemotherapeutic agents are not ideally effective drugs and have considerable resistance to chemotherapy. Exosome microRNA-103 plays an important role in the proliferation and invasion of liver cancer cells. The purpose of this article is to investigate the role and mechanism of exosome microRNA-103 in hepatocellular carcinoma cell proliferation and invasion. 84 patients with hepatocellular carcinoma diagnosed in a hospital from June 2017 to June 2020 were selected. The average age was 60.13±6.99 years. When the patient was fasting, 3 mL of peripheral venous blood was taken. And 50 healthy control groups were established, with an average age of 59.98±8.18 years old. 3 ml of peripheral venous blood was collected on an empty stomach to compare the cell proliferation rate and invasion rate. The results of the study showed that the number of stage III hepatocellular carcinoma cells invaded at 6h was 68.9, and it changed to 89.4 at 12h, and 106.4 at 24h; compared with that, the cell invasion rate in stage IV was higher. The number of stage IV hepatocellular carcinoma invasions at 6h was 68, which changed to 94.5 at 12h and 112.4 at 24h.

Ceramide synthase 3 affects invasion and metastasis of hepatocellular carcinoma via the SMAD6 gene.

Patients with hepatocellular carcinoma (HCC) have poor prognosis due to lack of early diagnosis and effective treatment. Therefore, there is an urgent need to better understand the molecular mechanisms associated with HCC and to identify effective targets for early diagnosis and treatment. This study is to explore the expression and biological role of ceramide synthase 3 (CerS3) in HCC. A total of 159 pairs of HCC tissues and adjacent non-tumor tissues were obtained from the patients underwent radical resection in Shenzhen People's Hospital, and the total RNA and proteins from HCC tissues and adjacent non-tumor tissues were obtained. The expression of CerS3 protein and mRNA in HCC was detected by immunohistochemistry, Western blotting and real-time PCR. In vitro experiments, Hep3B cells were divided into a control vector group and a CerS3 vector group, and the cells were transfected with retroviral vector containing control cDNA or CerS3 cDNA, respectively. HCCLM3 cells were divided into a normal control shRNA group and a CerS3 shRNA group, and the cells were transfected with lentiviral vectors containing normal control shRNA or CerS3 shRNA, respectively. MTT, EdU, Transwell and scratch method were used to detect cell proliferation, migration and invasion. RNA sequencing was performed to determine the downstream signal of CerS3. Compared with the corresponding adjacent tissues,the mRNA and protein levels of CerS3 were elevated in the HCC tissues, with significant difference (both P<0.05). The Univariate and multivariate analysis showed that the overall survival rate was significantly correlated with the presence of venous invasion (95% CI 1.8-9.2, P<0.01), TNM stage (95% CI 2.3-5.2, P<0.05), poor histological grade (95% CI 1.4-6.8, P<0.05), and CerS3 (95% CI 1.5-3.9, P<0.05). Furthermore, the high CerS3 expression levels in tumor tissues were significantly associated with shorter overall survival rates compared with the low CerS3 expression (P<0.05). Compared with the vector control group, the Hep3B cell viability, EdU positive cells, and migration and invasion cell numbers in the CerS3 vector group were significantly increased (all P<0.05). Compared with the shRNA normal control group, the HCCLM3 cell viability, EdU positive cells, and numbers of migrating and invasive cells in the CerS3 shRNA group were significantly lower (all P<0.05). The RNA sequencing confirmed that the small mothers against decapentaplegic family member 6 (SMAD6) gene as an oncogenic gene could promote the HCC metastasis. Clinically, the overexpression of CerS3 is closely related to poor clinical features and poor prognosis. Functionally, CerS3 participates in the proliferation, invasion and metastasis of liver cancer cells via activating SMAD6 gene.

MicroRNA214 expression inhibits HCC cell proliferation through PTK2b/ Pyk2.

MicroRNAs (miRNAs/miRs) are crucial regulatory molecules that act as the most significantly downregulated microRNAs in hepatocellular carcinoma (HCC). PTK2b/Pyk2 is a non-receptor protein tyrosine kinase, which plays an important role in the development and metastasis of cancer. In this study, we explored the expression level and functional relationship between MicroRNA-214 (miR-214) and PTK2b/ Pyk2 in liver cancer cells. For this purpose, we analyzed the expression of miR-214 and PTK2b/Pyk2 in 38 cases of HCC and paired non-neoplastic tissue specimens using real-time PCR. MTT, cell cycle and construct recombinant plasmids analysis were used to explore the effects of miR-214 and PTK2b/Pyk2 on liver cancer cell proliferation. Results showed that the expression level of mir-214 in liver cancer tissues and liver cancer cell lines was significantly lower than that in normal tissues and cells, while the expression of PTK2b/Pyk2 was significantly increased. The overexpression of mir-214 or inhibition PTK2b/Pyk2 inhibited the proliferation of HCC cells. This research showed that mir-214 has an inhibitory effect on liver cancer through the expression of PTK2b/Pyk2.

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway.

Objective To study the mechanism of curcumol affecting the proliferation and apoptosis of liver cancer cells through the DJ-1/PTEN/PI3K/AKT pathway. Method HepG2 cells were cultured in vitro, treated with curcumol at concentrations of 10, 30, and 100 μg/mL, and DMSO was used as a control. The levels of cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. RT-PCR and western blot were used to detect PTEN, p-AKT, DJ-1, and PI3K gene and protein expression changes. Result (1) Compared with the DMSO blank control group, the proliferation level of liver cancer cells in the 10 μg/mL curcumol group decreased, and the proportion of apoptosis increased (p <0.05). (2) Compared with the blank control group and the 10 and 30 μg/mL concentration groups, the proliferation level of liver cancer cells in the 100 μg/mL curcumol group was significantly reduced, and the proportion of cell apoptosis was significantly increased (p < 0.05). (3) Curcumol can significantly increase the expression of PTEN gene and protein in liver cancer cells and reduce the expression of DJ-1 and PI3K genes and protein in liver cancer cells (p < 0.05). Conclusion Curcumol can regulate DJ-1, PTEN, PI3K, and AKT signal transduction pathways, inhibit cell proliferation, and cause a significant increase in the proportion of cell apoptosis, and the pharmacodynamic effect of curcumol is dependent on the time and dose of action.

ApoM regulates PFKL through the transcription factor SREBF1 to inhibit the proliferation, migration and metastasis of liver cancer cells.

Apolipoprotein M (ApoM) is considered a protective factor that inhibits the occurrence and development of liver cancer, but the specific underlying mechanisms require further investigation. Previous studies have demonstrated that ApoM gene knockout promotes the expression of the transcription factor sterol regulatory element-binding protein 1 (SREBP1; also known as SREBF1) in the livers of mice. SREBF1 is closely associated with factors involved in fatty acid synthesis and has a role in the promotion of tumor progression. The present study initially confirmed that the expression levels of ApoM in cancer tissues were significantly decreased compared with those in normal tissue, while the expression levels of SREBF1 were significantly increased. In addition, ApoM gene knockout significantly increased the expression levels of SREBF1 and the key glycolytic enzyme ATP-dependent 6-phosphofructokinase, liver type (PFKL). Binding site prediction and a dual-luciferase reporter gene assay indicated that SREBF1 regulates the promoter region of PFKL. To the best of our knowledge, the present study was the first to propose the regulation of glycolytic enzyme transcription levels by SREBF1. Furthermore, cell proliferation and Transwell assays demonstrated that ApoM gene knockout increased the expression levels of SREBF1 and further enhanced the activity of the promoter region of PFKL, ultimately promoting the proliferation, migration and invasion of liver cancer cells.

Extracellular PKCδ signals to epidermal growth factor receptor for tumor proliferation in liver cancer cells.

Protein kinase C delta (PKCδ) is a multifunctional PKC family member and has been implicated in many types of cancers, including liver cancer. Recently, we have reported that PKCδ is secreted from liver cancer cells, and involved in cell proliferation and tumor growth. However, it remains unclear whether the extracellular PKCδ directly regulates cell surface growth factor receptors. Here, we identify epidermal growth factor receptor (EGFR) as a novel interacting protein of the cell surface PKCδ in liver cancer cells. Imaging studies showed that secreted PKCδ interacted with EGFR‐expressing cells in both autocrine and paracrine manners. Biochemical analysis revealed that PKCδ bound to the extracellular domain of EGFR. We further found that a part of the amino acid sequence on the C‐terminal region of PKCδ was similar to the putative EGFR binding site of EGF. In this regard, the point mutant of PKCδ in the binding site lacked the ability to bind to the extracellular domain of EGFR. Upon an extracellular PKCδ‐EGFR association, ERK1/2 activation, downstream of EGFR signaling, was apparently induced in liver cancer cells. This study indicates that extracellular PKCδ behaves as a growth factor and provides a molecular basis for extracellular PKCδ‐targeting therapy for liver cancer.

DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p.

Liver cancer is one of the most common and aggressive malignancies worldwide with poor prognosis. Studies on pathogenesis of liver cancer are urgently demanded to develop better treatment strategy. Here, we found that overexpression of DnaJ heat shock protein family (Hsp40) member A1 (DNAJA1) increased cell proliferation, invasion, and angiogenesis in Huh 7 and HepG2 cells, while depletion of DNAJA1 in MHCC-97H and HCC-M3 showed opposite effects. In vivo functional assays indicated that DNAJA1 promoted tumor growth and pulmonary metastasis in mice. Mechanistically, as a direct target of miR-205-5p, DNAJA1 promoted proliferation and metastasis of liver cancer cells by stabilizing eukaryotic elongation factor 1A1 (EF1A1). Moreover, DNAJA was markedly upregulated in liver cancer tissues (P < 0.05) and was significantly associated with poor prognosis. And its expression was correlated with differentiation (P < 0.001), dissemination (P < 0.001), and serum AFP (P = 0.029). The mRNA levels of miR-205-5p and DNAJA1 were negatively correlated in liver cancer. In conclusion, our study reveals that DNAJA1 acts as an oncogene in liver cancer via miR-205-5p/EF1A1 axis and might be a potential biomarker to predict the prognosis for liver cancer patients.

Tumor-matrix interaction induces phenotypic switching in liver cancer cells.

Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix. Liver cancer cells grown on collagen 1-coated plates showed upregulation of cholangiocytic marker expression but downregulation of hepatocytic marker expression. Three-dimensional sphere culture and Boyden chamber assay showed enhanced invasion and migration ability in collagen 1-conditioned liver cancer cells. Interaction with collagen 1 reduced liver cancer cell proliferation. RNA sequencing showed that in the liver cancer cells, collagen 1 upregulated cell cycle inhibitor expression and cell-matrix interaction, tumor migration, and angiogenesis pathways, but downregulated liver metabolic function pathways. Cholangiocytic differentiation and invasiveness induced by collagen 1 was mediated by the mitogen-activated protein kinase (MAPK) pathway, which was regulated by cell-matrix interaction-induced Src activation. Analysis of the Cancer Genome Atlas cohort showed that collagen 1 induced and suppressed genes were highly enriched in ICC and HCC, respectively. In HCC samples, collagen 1-regulated genes were strongly coexpressed and correlated with COL1A1 expression. Liver cancer cell-matrix interaction induces cholangiocytic differentiation and switches liver cancer cells from a proliferative to an invasive phenotype through the Src/MAPK pathway, which may partly explain the differences in the behaviors of HCC and ICC.

Circular RNA circRNA-0039459 promotes the migration, invasion, and proliferation of liver cancer cells through the adsorption of miR-432

ABSTRACT This study aimed to investigate the molecular mechanism of circular RNA circ-0039459 and its effects on the apoptosis, proliferation, invasion, and migration of hepatocellular carcinoma cells. The expression of circ-0039459, miR-432, and synoviolin 1 (SYVN1) mRNA was determined using real-time quantitative reverse transcription PCR. Cell proliferation was detected by cell counting kit-8 assay, and the apoptosis rate was detected using flow cytometry. Cell migration and invasion were detected using Transwell assay. The expression of E-cadherin, N-cadherin, and vimentin was detected using western blot. The targeting relationship between circ-0039459 and miR-432 as well as that between miR-432 and SYVN1 were detected using the dual-luciferase reporter and RNA pull-down assays. We found that circ-0039459 and SYVN1 mRNA were highly expressed, whereas miR-432 was lowly expressed in hepatocellular carcinoma cells and tissues. After treatment with ribonuclease R or actinomycin D, the expression of linear RNA was reduced, whereas that of circular RNA was not significantly changed. circ-0039459 knockdown or miR-432 overexpression can inhibit cell proliferation, invasion, and migration and the expression of N-cadherin and vimentin proteins in carcinoma cells as well as promote apoptosis and increase the E-cadherin level. circ-0039459 targeted and regulated miR-432, which targeted and regulated SYVN1. The decreased miR-432 expression reversed the effects of circ-0039459 knockout in cancer cells. Furthermore, SYVN1 overexpression reversed the effect of miR-432 overexpression in hepatoma cells. Hence, circ-0039459 can affect the proliferation, apoptosis, migration, and invasion of hepatocellular carcinoma cells through the adsorption of miR-432, thereby regulating the expression of SYVN1.

β-Patchoulene represses hypoxia-induced proliferation and epithelial-mesenchymal transition of liver cancer cells

ABSTRACT Hepatocellular carcinoma (HCC) is a malignant tumor originating from liver epithelial cells with a high clinical mortality rate. β-Patchoulene (β-PAE) is a compound extracted from patchouli, which has analgesic, anti-inflammatory and antioxidant effects. This research aims to probe the impacts of β-PAE on hypoxia-induced HCC cell proliferation and epithelial-mesenchymal transition (EMT). Firstly, hypoxic injury models were constructed in HCC Huh-7 and MHCC97 cells, and the hypoxic injury cell models were then treated with different concentrations of β-PAE. The cell viability, proliferation, migration, invasion and apoptosis were checked by the cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell assay, flow cytometry and terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression of Survivin protein, EMT markers and the NF-κB/HIF-1α pathway was gauged by Western blot (WB) or cellular immunofluorescence or reverse transcription-polymerase chain reaction (RT-PCR). The in-vivo experiment was conducted to confirm the anti-tumor role of β-PAE. As a result, β-PAE abated hypoxia-induced HCC cell growth, proliferation, migration, invasion and EMT and facilitated apoptosis in vitro and in vivo dose-dependently. Further mechanism studies displayed that β-PAE inactivated the NF-κB/HIF-1α pathway, and HIF-1α activation significantly reversed the β-PAE-mediated tumor inhibition. β-PAE repressed the proliferation and EMT of hypoxia-induced HCC cells by choking the NF-κB/HIF-1α pathway, suggesting that β-PAE was a potential drug for HCC treatment.

Anti-Liver Cancer Activity of a New Compound Extracted from Populus pruinosa and Phylogenetic Analysis

Populus pruinosa is a fragile poplar species separated from other poplar trees. It is specifically adapted to tropical areas and utilized as a conventional medicine. It is an important medicinal plant for the treatment of cancer. A new compound was extracted from P. pruinosa. Its application value for the treatment of liver cancer was then explored. The corresponding mechanism was also determined. After treatment with this compound, CCK-8 was detected and the proliferation of liver cancer cells was examined. Furthermore, the percentage of hepatocyte apoptosis was calculated via Annexin V-FITC/PI apoptosis analysis. The total sequence of the chloroplast genome of P. pruinosa was determined by terminal sequencing with Illumina. Neighbor-joining phylogenetic analysis suggested that P. cathayana and P. pruinosa cluster together as the sister groups to other poplar species.

Overexpression of SSR2 promotes proliferation of liver cancer cells and predicts prognosis of patients with hepatocellular carcinoma.

Signal Sequence Receptor Subunit 2 (SSR2) is a key endoplasmic reticulum gene involved in protein folding and processing. Previous studies found that it was upregulated in several cancers, but its precise role in hepatocellular carcinoma (HCC) remains unclear. To have a better understanding of this gene in HCC, we examined the expression of SSR2 in HCC tissues by analysing The Cancer Genome Atlas (TCGA) data and immunohistochemistry. We also assessed the association between SSR2 expression and clinicopathological characteristics of HCC patients and patient survival. Potential function of SSR2 was predicted through GSEA and protein–protein interaction analysis. MTT, flowcytometry, transwell and a nude mice xenograft model were employed to investigate the biological functions in vivo and in vitro. The results showed that the expression of SSR2 was significantly increased in HCC tissues, and SSR2 expression was associated with several clinical characteristics. In addition, patients with higher SSR2 expression had poorer survival. Enrichment analysis suggested that SSR2 was probably involved in biological process or signalling pathways related to G2/M checkpoint, passive transmembrane transporter activity, ATF2_S_UP. V1_UP and ncRNA metabolic process. Further experimental study showed that SSR2 knockdown inhibited cell proliferation, migration and invasion ability and promoted apoptosis and cell cycle arrest in vitro. Moreover, downregulation of SSR2 also repressed the growth of HepG2 cells in vivo. In conclusion, our study suggests that SSR2 may act as an oncogene in HCC.

BAP31 Promotes Proliferation, Invasion, and Metastasis of Liver Cancer Cells via Activating PI3K/AKT Pathway.

Background Many breakthroughs have been made in the clinical treatment of liver cancer, but there are still many liver cancer patients with limited treatment methods. Therefore, it is very important to find targets for early diagnosis and specific treatment of liver cancer. Methods During the operation, 32 pairs of tumor tissues and corresponding normal liver tissues were acquired from patients. The mRNA expression was measured by qPCR. The protein expression was evaluated via Western blot. Flow cytometry assay was performed to measure the cells apoptosis. CCK-8 assay was performed to detect cell proliferation. Transwell chamber assay was applied to detect migration and invasion of SNU-449 cells. Results BAP31 was upregulated in liver cancer tissues and cells. Knockdown of BAP31 repressed cell proliferation and enhanced cell apoptosis of liver cancer. Knockdown of BAP31 apparently upregulated apoptosis-related proteins (Bax and Caspase-3), while it downregulated antiapoptotic proteins (Bcl-2). Knockdown of BAP31 repressed migration and invasion of SNU-449 cells. In contrast with the control and si-NC group, protein expression of MMP-2 and MMP-9 was obviously lower after si-BAP31 transfection of cells. Knockdown of BAP31 repressed PI3K/AKT signaling pathways in liver cancer cells. Conclusion Knockdown of BAP31 repressed cell proliferation, migration, and invasion in liver cancer by suppressing PI3K/AKT/mTOR signaling pathways.

High expression of H2A histone family member Y promotes the proliferation and autophagy of hepatocellular carcinoma cells

ABSTRACT Hepatocellular carcinoma is a common malignant tumor and the third most common cause of cancer-related deaths. In this study, we selected H2AFY as a potential oncogene from three online databases, and verified differential expression between normal and liver cancer tissues. Moreover, H2AFY expression was significantly correlated with the clinical characteristics and the survival of liver cancer patients. H2AFY expression was correlated with poor prognosis of liver cancer patients. H2AFY expression was also significantly higher in liver cancer cells. Knockdown and overexpression of H2AFY in liver cancer cells showed that H2AFY promoted the proliferation and clone formation of liver cancer cells but had no significant effects on the migration and invasion ability of liver cancer cells. Western blot analysis, immunohistochemistry, and immunofluorescence double staining confirmed that H2AFY upregulated LC3 and p62 expression in liver cancer tissues and cells. In conclusion, H2AFY is highly expressed in liver cancer cells and tissues, and promotes the proliferation and autophagy of liver cancer cells. H2AFY is a potential target for liver cancer therapy. Abbreviations: APLF: aprataxin pnk-like factor; HCC: Hepatocellular carcinoma; H2AFY: H2A histone family member Y