S100 Calcium Binding Protein A10, A Novel Oncogene, Promotes the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma.
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ABSTRACT:
SUBMITTER: Zhou X
PROVIDER: S-EPMC8226228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The prognostic biomarkers and potential therapy targets are urgently needed in hepatocellular carcinoma (HCC). In this article, we report the expression of TUBA1C was significantly increased in HCC on mRNA and protein level, and this finding was further validated in another two independent datasets. Survival analysis was also implemented on these three datasets, and TUBA1C high expression group was detected to have relative shorter survival time. Furthermore, the metastatic ability is increased along with TUBA1C abundance, according to protein abundance evaluation of normal-tumor-portal vein tumor thrombus pairs, and mRNA comparison between metastasis-averse HCC and metastasis-incline HCC. Correlation analysis was implemented and TUBA1C expression was shown to be significantly associated with recurrence, embolus, and AFP level. Proliferation and migration assays following knock down of TUBA1C in two cell lines, HCCLM3 and PLC, revealed that down-regulation of TUBA1C significantly reduces proliferation and migration in HCC cells. in vivo study also showed the similar results. Gene Set Enrichment Analysis (GSEA) comparing the TUBA1C-low and TUBA1C-high group indicates that KEGG pathways including "cell cycle", "DNA replication", and "proteasome" were significantly enriched in TUBA1C-high group. In conclusion, prognostic biomarker and oncogene TUBA1C promotes migration and proliferation of hepatocellular carcinoma cells, probability via cell cycle signaling pathway.
| S-EPMC5707094 | biostudies-literature
Project description:Epidermal growth factor receptor (EGFR) is frequently aberrantly expressed in cancer, and abnormal signalling downstream of this receptor contributes to tumour growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. Aberrant signalling downstream of this receptor contributes to tumour invasion. We previously reported that EGFRvIII can promote hepatocellular carcinoma (HCC) invasion. However, little is known concerning the mechanisms underlying EGFRvIII-mediated increases in cell motility and invasion in HCC. In this study, we observed that S100A11 was significantly upregulated in Huh-7 cells that overexpressed EGFRvIII. Moreover, S100A11 expression was elevated in HCC tissue samples (68.6%; 35/51), and this elevation was correlated with EGFRvIII expression (p?=?0.0020; n?=?20). Furthermore, the overexpression of S100A11 can promote HCC cell invasiveness, whereas siRNA against S100A11 can suppress the invasiveness of HCC cells stably transfected with EGFRvIII. Additionally, STAT3 inhibitors can block S100A11 expression and S100A11 promoter activity in HCC cells with stable overexpression of EGFRvIII. Furthermore, mutation in STATx binding sites could abolish the S1000A11 promoter activity stimulation by EGFRvIII. Taken together, the results demonstrate that the EGFRvIII-STAT3 pathway promotes cell migration and invasion by upregulating S100A11.
| S-EPMC3869758 | biostudies-literature
Project description:The tumour susceptibility gene 101 (TSG101) is reported to play important roles in the development and progression of several human cancers. However, its potential roles and underlined mechanisms in human hepatocellular carcinoma (HCC) are still needed to be further clarified. In the present study, we reported that knock down of TSG101 suppressed the proliferation, migration and invasion of HCC cells, while overexpression of TSG101 facilitated them. Molecularly, the results revealed that knock down of TSG101 significantly decreased the cell cycle related regulatory factor p53 and p21. In another point, knock down of TSG101 also obviously decreased the level of metallopeptidase inhibitor TIMP1 (Tissue inhibitors of metalloproteinases 1), which results in inhibition of MMP2, MMP7 and MMP9. In contrast, overexpression of TSG101 had opposite effects. The iTRAQ proteomics analysis identified that oncogenic protein PEG10 (Paternally expressed gene 10) might be a potential downstream target of TSG101. Further investigation showed that TSG101 interacted with PEG10 and protected it from proteasomal degradation thereby regulating the expression of p53, p21 and MMPs. Finally, we found that both TSG101 and PEG10 proteins are up-regulated and presented a direct correlation in HCC patients. In conclusion, these results suggest that TSG101 is up-regulated in human HCC patients, which may accelerate the proliferation, migration and invasion of HCC cells through regulating PEG10.
| S-EPMC6307771 | biostudies-literature
Project description:BackgroundIn recent years, microRNA-1-3p (miR-1-3p) has been linked to the progression of multiple cancers, whereas little is known about its role in hepatocellular carcinoma (HCC). Herein, we investigated the function of miR-1-3p in HCC, and its regulatory function on origin recognition complex subunit 6 (ORC6).MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was performed for detecting the expression levels of miR-1-3p and ORC6 mRNA in HCC samples and cell lines. ORC6 expression at the protein level was quantified by Western blot. After gain-of-function and loss-of-function models were established, cell counting kit-8 (CCK-8) assays, Transwell assays, flow cytometry, and 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed for examining cell proliferation, migration, invasion, cell cycle, and apoptosis. The targeting relationship between miR-1-3p and ORC6 was confirmed with bioinformatic analysis and dual-luciferase reporter assays.ResultsThe expression of miR-1-3p was reduced in HCC samples and cell lines. Overexpression of miR-1-3p suppressed the proliferation, migration, and invasion, and induced cell-cycle arrest and apoptosis of HCC cells, whereas the opposite effects were induced by miR-1-3p inhibition. ORC6 is identified as a novel target of miR-1-3p, the expression of which is negatively correlated with miR-1-3p expression in HCC tissues. ORC6 overexpression facilitated the proliferation, migration, invasion, and cell cycle progression, and reduced apoptosis of HCC cells, whereas the opposite effects were induced by ORC6 knockdown. What is more, ORC6 overexpression counteracted the biological functions of miR-1-3p in HCC cells.ConclusionMiR-1-3p targets ORC6 to suppress the proliferation, migration, invasion, and cell cycle progression, and promote apoptosis of HCC cells.
| S-EPMC8358308 | biostudies-literature
Project description:BackgroundHigh RSPH14 expression appears to be related to poor prognosis of hepatocellular carcinoma (HCC). This study aimed to investigate the possible roles of RSPH14 in the proliferation, apoptosis, and invasion of HCC cells.MethodsThe UALCAN database and Kaplan-Meier Plotter were used to evaluate the expression level and prognostic role of RSPH14 in HCC. Lentiviral vectors containing shRNA against RSPH14 were constructed to transfect the BEL-7404 and SMMC-7721 HCC cell lines. Cell proliferation was investigated by BrdU, MTT, and colony-formation assays. Apoptosis was detected using flow cytometry. Cell migration and invasion were evaluated using the scratch wound-healing and Transwell assays. Immunohistochemistry and western blot were used to determine the expression levels of the proteins. The function of RSPH14 in vivo was evaluated using a xenograft mouse model.ResultsThe expression of RSPH14 was higher in HCC tumor tissues than in adjacent normal tissues and was closely related to unfavorable prognostic factors and poorer survival (all P < 0.05). Knockdown of RSPH14 inhibited the cell proliferation, migration, and invasion of HCC cells and promoted apoptosis (all P < 0.05). Knockdown of RSPH14 inhibited tumor growth in vivo (P < 0.05). RSPH14 knockdown led to decreased expression of RelA (NF-κBp65), CDH2, and AKT1, thereby affecting the functions of the HCC cells (all P < 0.05). RelA overexpression could abate the inhibitory effect of BEL-7404 cell proliferation caused by RSPH14 depletion.ConclusionKnockdown of RSPH14 could decrease cell proliferation, migration, and invasion and increase apoptosis of HCC cells by inhibiting RelA expression. RSPH14 could be a new treatment target for HCC.
| S-EPMC8933878 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is a highly metastatic tumor that occurs frequently in Southeast Asia, particularly including southern China. Epstein-Barr virus infection is well established as a primary cause of NPC; nevertheless, the mechanisms underlying NPC pathogenesis remain largely unknown. In our previous study, we conducted whole-genome sequencing to screen for genomic variations that were associated with NPC. Of the resultantly identified variations, glypican-6 (GPC6), was shown, for the first time, to be frequently mutated in NPC. In the present study, we verified this finding and conducted a series of functional experiments, which demonstrated that GPC6 promotes the migration, invasion, and proliferation of NPC cells in vitro. Thus, the present study identified novel biological functions for GPC6 in NPC, and thus, showed that GPC6 may be a promising potential therapeutic target for this disease.
| S-EPMC6692608 | biostudies-literature
Project description:Exportin-T (XPOT) belongs to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up-regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expression of XPOT in HCC indicated worse prognosis via bioinformatics analysis. Consistently, immunohistochemical staining of 95 pairs of tumors and adjacent normal liver tissues (ANLT) also showed up-regulation of XPOT. Small interfering (si) RNA transfection was used to down-regulate XPOT in HepG2 and 7721 cell lines. Cell Counting Kit-8 (CCK8) assays were performed to analyze cell proliferation. Cell migration and invasion were measured by scratch wound healing assays and migration assays. Subcutaneous xenograft models were using to explore the role of XPOT in tumor formation in vivo. Down-regulation of XPOT significantly inhibited tumor proliferation and invasion in vitro and vivo. Gene set enrichment analysis (GSEA) results indicated that XPOT may affect tumor progression through cell cycle and ubiquitin-mediated proteolysis. Furthermore, knockdown of XPOT caused a block in G0/G1 phase as evidenced by down-regulation of cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), CyclinA1 (CCNA1), CyclinB1 (CCNB1), CyclinB2 (CCNB2), and CyclinE2 (CCNE2) in HCC cells. In conclusion, our findings indicate that XPOT could serve as a novel biomarker for prognoses and a potential therapeutic target for patients with HCC.
| S-EPMC6587849 | biostudies-literature
Project description:Background:Taurine upregulated gene 1 (TUG1) has been recognized as a novel oncogenic gene. The current study was established to explore the function and regulatory mechanism of TUG1 in hepatocellular carcinoma (HCC). Methods:Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of TUG1, miR-29c-3p, and COL1A1 in tissues and cell lines. MTT assay, wound-healing and transwell assay were utilized for the detection of cell viability, migration and invasion, respectively. The interactions between miR-29c-3p and TUG1/COL1A1 were predicted by starBase v2.0 (http://starbase.sysu.edu.cn/) and verified by the dual-luciferase reporter or RNA immunoprecipitation assay. Western blot assay was performed to determine the protein levels of COL1A1, cyclin D1, E-cadherin, N-cadherin, Bcl-2, and Bax. Results:Dramatically increased expression of TUG1 was noticed in HCC tissues and cell lines. TUG1 knockdown restrained the proliferation, migration, and invasion, and promoted the apoptosis of HCC cells. TUG1 targeted miR-29c-3p and inhibited miR-29c-3p expression. Overexpression of miR-29c-3p inhibited the proliferation, migration and invasion of HCC cells. MiR-29c-3p directly targeted COL1A1 and down-regulated COL1A1 expression. In addition, downregulation of miR-29c-3p and upregulation of COL1A1 both reversed the effects of TUG1 knockdown on the proliferation, apoptosis, migration, and invasion of HCC cells. Conclusion:TUG1 could promote the proliferation, migration and invasion of HCC cells through regulating miR-29c-3p/COL1A1 axis. This novel finding might provide a latent target for the treatment of HCC.
| S-EPMC7425090 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC), with life-threatening malignant behaviours, often develops distant metastases and is the fourth most common primary cancer in the world, having taken millions of lives in Asian countries such as China. The novel miR-3677-3p is involved in a high-expression-related poor prognosis in HCC tissues and cell lines, indicating oncogenesis functions in vitro and in vivo. Initially, we confirmed the inhibition of proliferation, migration and invasion in miR-3677-3p knock-down MHCC-97H and SMMC-7721 cell lines, which are well known for their high degree of invasiveness. Then, we reversed the functional experiments in the low-miR-3677-3p-expression Hep3B cell line via overexpressing miR-3677-3p. In nude mice xenograft and lung metastasis assays, we found suppressor behaviours, smaller nodules and low density of organ spread, after injection of cells transfected with shRNA-miR-3677-3p. A combination of databases (Starbase, TargetScan and MiRgator) illustrated miR-3677-3p targets, and it was shown to suppress the expression of SIRT5 in a dual-luciferase reporter system. To clarify the conclusions of previous ambiguous research, we up-regulated SIRT5 in Hep3B cells, and rescue tests were established for confirmation that miR-3677-3p suppresses SIRT5 to enhance the migration and invasion of HCC. Interestingly, we discovered hypoxia-induced miR-3677-3p up-regulation benefited HCC malignancy and invasiveness. In conclusion, the overexpression of miR-3677-3p mediated SIRT5 inhibition, which could increase proliferation, migration and invasion of HCC in hypoxic microenvironments.
| S-EPMC7412699 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a common malignancy that is associated with a poor prognosis. The extensively studied TGF-β pathway is mediated by SMAD proteins. FXR1, a protein-coding gene belonging to the fragile X-related (FXR) family, is involved in the TGF-β pathway. Previous studies have shown that FXR1 promotes the proliferation, invasion, and migration of colorectal cancer cells. The aim of the present study was to explore the effects of FXR1 on HCC via the TGF-β/SMAD signaling pathway. Immunohistochemical analysis was used to detect the expression of FXR1 in HCC and normal tissues. Western blotting was used to detect protein expression levels in the HCC cell lines, cell migration and invasion were assessed using Transwell assays, and cell proliferation was assessed using a colony formation assay. The ability of the liver cancer cells to grow in vivo was investigated using a nude mouse tumor-bearing model. The results showed that FXR1 expression was upregulated in HCC tissues compared with normal tissues. Knockdown of FXR1 resulted in reduced expression of SMAD2/3 and EMT-related proteins in HCC cells. In addition, FXR1 knockdown inhibited the proliferation, migration, and invasion of HCC cells. FXR1 knockdown also reversed the promoting effect of TGF-β on the invasive ability of HCC cells. Knockdown of SMAD2/3 reversed the increase in HCC cell invasion induced by FXR1 overexpression. Finally, upregulated FXR1 expression was associated with a poorer prognosis in patients with HCC. In conclusion, FXR1 promoted HCC proliferation, migration, and invasion through the regulation of SMAD2/3.
| S-EPMC9713760 | biostudies-literature