DLX6-AS1 promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1.
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ABSTRACT:
SUBMITTER: Wu Q
PROVIDER: S-EPMC7012178 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Gastric cancer (GC) is the fourth most common malignant neoplasm and the second leading cause of cancer death. Identification of key molecular signaling pathways involved in gastric carcinogenesis and progression facilitates early GC diagnosis and the development of targeted therapies for advanced GC patients. Emerging evidence has revealed a close correlation between forkhead box (FOX) proteins and cancer development. However, the prognostic significance of forkhead box S1 (FOXS1) in patients with GC and the function of FOXS1 in GC progression remain undefined. In this study, we found that upregulation of FOXS1 was frequently detected in GC tissues and strongly correlated with an aggressive phenotype and poor prognosis. Functional assays confirmed that FOXS1 knockdown suppressed cell proliferation and colony numbers, with induction of cell arrest in the G0/G1 phase of the cell cycle, whereas forced expression of FOXS1 had the opposite effect. Additionally, forced expression of FOXS1 accelerated tumor growth in vivo and increased cell migration and invasion through promoting epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, the core promoter region of FOXS1 was identified at nucleotides -660~ +1, and NFKB1 indirectly bind the motif on FOXS1 promoters and inhibit FOXS1 expression. Gene set enrichment analysis revealed that the FOXS1 gene was most abundantly enriched in the hedgehog signaling pathway and that GLI1 expression was significantly correlated with FOXS1 expression in GC. GLI1 directly bound to the promoter motif of FOXS1 and significantly decreased FOXS1 expression. Finally, we found that miR-125a-5p repressed FOXS1 expression at the translational level by binding to the 3' untranslated region (UTR) of FOXS1. Together, these results suggest that FOXS1 can promote GC development and could be exploited as a diagnostic and prognostic biomarker for GC.
| S-EPMC6437149 | biostudies-literature
Project description:Purpose:Gastric cancer (GC) is the fifth most common tumor in the world, and most patients with GC have a poor prognosis. This study aimed to explore the biological influence and mechanism of LINC01272 in GC. Materials and Methods:Using bioinformatic analyses, we investigated the expression of LINC01272 in TCGA database and predicted the biological functions and mechanism of LINC01272 in GC. Then, we detected the expression of LINC01272 in GC cell lines, GC tissues, and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Finally, we explored the migration and invasion ability of LINC01272 by wound-healing and Transwell assays and examined the expression of epithelial-mesenchymal transition (EMT)-related proteins through Western blotting. Results:We found that LINC01272 was upregulated in GC and was associated with GC staging and lymph node metastasis. The results of wound-healing and Transwell assays revealed that the LINC01272 was closely related to GC cell migration and invasion. LINC01272 knockdown inhibited the migration and invasion ability of GC cells by reducing the expression of EMT-related proteins. Overexpression of LINC01272 had the opposite effect. Conclusion:Together, our results showed that LINC01272 promoted GC metastasis ability by regulating the expression of EMT-related proteins and could serve as a potential diagnostic biomarker for GC.
| S-EPMC7184168 | biostudies-literature
Project description:TAFA chemokine like family member 5 (TAFA5), a TAFA family member that encodes small secreted proteins in the central nervous system, has been demonstrated to have increased expression in human malignancies. However, the expression and function of TAFA5 in gastric cancer (GC) remains unclear. In the present study, public datasets and human GC samples were used to determine the TAFA5 expression levels. The results revealed that TAFA5 was upregulated in GC when compared with adjacent normal tissues. Overexpression of TAFA5 in GC was associated with poor differentiation, and worse tumor, nodal and metastasis stages. In addition, high TAFA5 expression was correlated with unfavorable patient prognoses. In vitro experiments indicated that downregulation of TAFA5 inhibited the proliferation and migration of GC cell lines. Finally, the results from gene set enrichment analysis using data from The Cancer Genome Atlas revealed that TAFA5 expression was significantly correlated with genes associated with epithelial?mesenchymal transition, which was further confirmed by western blot analysis. In conclusion, the results of the present study suggested that TAFA5 had significant effects on GC progression, suggesting that it may serve as a potential therapeutic target for GC therapy.
| S-EPMC6797941 | biostudies-literature
Project description:BackgroundThe crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gastric cancer (GC) remained a riddle.MethodsRT-qPCR was used to examine the expression of NFIC/LBX2-AS1/miR-491-5p/ZNF703 in GC cell lines. The functions of LBX2-AS1 in GC were appraised by colony formation, EdU, flow cytometry analysis, transwell and wound healing assays. Luciferase reporter, ChIP and RNA pull down assays were utilized to evaluate the interactions among genes.ResultsLBX2-AS1 was up-regulated in GC cell lines. Knockdown of LBX2-AS1 repressed the proliferative, migratory, and invasive abilities of GC cells. Moreover, LBX2-AS1 was transcriptionally activated by NFIC. And LBX2-AS1 could bind with miR-491-5p. Besides, miR-491-5p depletion or ZNF703 upregulation could counteract the repressing effects of LBX2-AS1 silence on GC progression.ConclusionIn a word, LBX2-AS1 up-regulated by NFIC promoted GC progression via targeting miR-491-5p/ZNF703, implying LBX2-AS1 was an underlying treatment target for GC patients.
| S-EPMC7183605 | biostudies-literature
Project description:Previous research has found that miRNA-20b is highly expressed in gastric cancer (GC), however, its function and underlying mechanism are not clear. Wnt signaling pathway, implicated in tumorigeneisis, is activated in more than 30% of GC. We would like to characterize the biological behavior of miRNA-20b in terms of modulating Wnt/β-catenin signaling and EMT. We showed that miRNA-20b inhibitors suppressed Topflash/Fopflash dependent luciferase activity and the β-catenin nuclear translocation, resulting in inhibition of Wnt pathway activity and EMT. SUFU, negatively regulating Wnt and Hedgehog signaling pathway, was proved to be targeted by miRNA-20b. Moreover, additional knockdown of SUFU alleviated the inhibitory effect on Wnt pathway activity, EMT, cell proliferation/migration and colony formation caused by miRNA-20b inhibition. In summary, miRNA-20b is an oncogenic miRNA and promoted cell proliferation, migration and EMT in GC partially by activating Wnt pathway via targeting SUFU.
| S-EPMC8065298 | biostudies-literature
Project description:BackgroundAt present, gastric cancer (GC) is a serious threat to human life and health. Non-coding circular RNAs (circRNAs) have been found abnormal expression in multiple tumors. However, circRNAs remain largely unknown in tumor progression. In the present study, we mainly examined the expression, function, and molecular mechanisms of a new circRNAs (hsa_circ_101882) in GC.Materials and methodsThe expression of hsa_circ_101882 in GC tissue, corresponding adjacent normal tissues, and GC cell lines was examined by RT-PCR. The function of hsa_circ_101882 in GC was evaluated by MTT assay, cell migration, and invasion assay, colony formation assay, and flow cytometric assay. The effect of hsa_circ_101882 on epithelial-to-mesenchymal transition (EMT)-related gene expression was detected by RT-PCR and Western blot.ResultsHsa_circ_101882 expression levels were significantly increased in GC tissue and GC cell lines. Functionally, low expression of hsa_circ_101882 revealed anti-tumor effects via inhibiting cell growth, migration, and invasion and promoting cell apoptosis. Mechanically, the dysregulated expression of hsa_circ_101882 affects EMT signaling pathway, which was examined by detecting E-cadherin, N-cadherin, vimentin, and Snail expression levels.ConclusionsTherefore, our research reveals that hsa_circ_101882 is considered a metastasis promoter by activating EMT and may serve as a critical oncogene and potential new biomarker in GC.
| S-EPMC6868453 | biostudies-literature
Project description:BackgroundStructural maintenance of chromosomes protein 1 A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participates in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC).Materials and methodsRT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed. Furthermore,the mechanism of SMC1A action was investigated.ResultsSMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS cells remarkably promoted cell proliferation in vitro and in vivo, migration and invasion, Conversely, knockdown of SMC1A in HGC27 cells inhibited cell proliferation, migration and invasion. Moreover, it's observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAIL.ConclusionOur study revealed that SMC1A promotes EMT process by upregulating SNAIL, which contributes to gastric cancer cell proliferation, migration and invasion. Therefore, targeting SMC1A may be a potential strategy to improve GC therapy.
| S-EPMC10401881 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions and targets of lncRNAs in neuroblastoma (NB) progression still remain to be determined. In this study, we aimed to investigate the effect of lncRNA DLX6 antisense RNA 1 (DLX6-AS1) on NB and the underlying mechanism involved.MethodsThrough mining of public microarray datasets, we identify aberrantly expressed lncRNAs in NB. The gene expression levels were determined by quantitative real-time PCR, and protein expression levels were determined by western blot assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, wound-healing assay, transwell invasion assays and flow cytometry analysis were utilized to examine cell proliferation, migration, invasion and apoptosis. Luciferase reporter assay was performed to confirm the interaction between DLX6-AS1and its potential targets. Tumor xenograft assay was used to verify the role of DLX6-AS1 in NB in vivo.ResultsWe identified DLX6-AS1 was upregulated in NB by using a public microarray dataset. The expression of DLX6-AS1 was increased in NB tissues and derived cell lines, and high expression of DLX6-AS1 was positively correlated with advanced TNM stage and poor differentiation. Knockdown of DLX6-AS1 induced neuronal differentiation, apoptosis and inhibited the growth, invasion, and metastasis of NB cells in vitro and impaired tumor growth in vivo. MiR-107 was the downstream target of DLX6-AS1. MiR-107 was found to target brain-derived neurotrophic factor (BDNF) which is an oncogene in NB. Knockdown of miR-107 or overexpression of BDNF reversed the suppression of NB progression caused by DLX6-AS1 silence.ConclusionOverall, our finding supports that DLX6-AS1 promotes NB progression by regulating miR-107/BDNF pathway, acting as a novel therapeutic target for NB.
| S-EPMC6880520 | biostudies-literature
Project description:Eukaryotic translation elongation factor 1δ (EEF1D), a subunit of the elongation factor 1 complex of proteins, mediates the elongation process of protein synthesis. Besides this canonical role, EEF1D was found overexpressed in many tumors, like hepatocarcinomas and medulloblastomas. In the present study, we demonstrated for the first time that EEF1D may interact with other putative proteins to regulate cell proliferation, migration, and invasion through PI3K/Akt and EMT pathways in glioma. Furthermore, knockdown of EEF1D could reduce cell proliferation and impaired epithelial-mesenchymal transition (EMT) phenotypes, including cell invasion. Taken together, these results indicate that EEF1D and its partner proteins might play a critical role in glioma and serve as a potential therapeutic target of glioma.
| S-EPMC7533006 | biostudies-literature
Project description:BackgroundBladder cancer is the most common human urological malignancies with poor prognosis, and the pathophysiology of bladder cancer involves multi-linkages of regulatory networks in the bladder cancer cells. Recently, the long noncoding RNAs (lncRNAs) have been extensively studied for their role on bladder cancer progression. In this study, we evaluated the expression of DLX6 Antisense RNA 1 (DLX6-AS1) in the cancerous bladder tissues and studied the possible mechanisms of DLX6-AS1 in regulating bladder cancer progression.MethodsGene expression was determined by qRT-PCR; protein expression levels were evaluated by western blot assay; in vitro functional assays were used to determine cell proliferation, invasion and migration; nude mice were used to establish the tumor xenograft model.ResultsOur results showed the up-regulation of DLX6-AS1 in cancerous bladder cancer tissues and bladder cell lines, and high expression of DLX6-AS1 was correlated with advance TNM stage, lymphatic node metastasis and distant metastasis. The in vitro experimental data showed that DLX6-AS1 overexpression promoted bladder cancer cell growth, proliferation, invasion, migration and epithelial-to-mesenchymal transition (EMT); while DLX6-AS1 inhibition exerted tumor suppressive actions on bladder cancer cells. Further results showed that DLX6-AS1 overexpression increased the activity of Wnt/β-catenin signaling, and the oncogenic role of DLX6-AS1 in bladder cancer cells was abolished by the presence of XAV939. On the other hand, DLX6-AS1 knockdown suppressed the activity of Wnt/β-catenin signaling, and the tumor-suppressive effects of DLX6-AS1 knockdown partially attenuated by lithium chloride and SB-216763 pretreatment. The in vivo tumor growth study showed that DLX6-AS1 knockdown suppressed tumor growth of T24 cells and suppressed EMT and Wnt/β-catenin signaling in the tumor tissues.ConclusionCollectively, the present study for the first time identified the up-regulation of DLX6-AS1 in clinical bladder cancer tissues and in bladder cancer cell lines. The results from in vitro and in vivo assays implied that DLX6-AS1 exerted enhanced effects on bladder cancer cell proliferation, invasion and migration partly via modulating EMT and the activity of Wnt/β-catenin signaling pathway.
| S-EPMC6880345 | biostudies-literature