Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 inhibits cell proliferation and invasion in human colorectal cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Ye K
PROVIDER: S-EPMC5556637 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Gliomas are the most common and aggressive type of primary adult brain tumor. Although high expression and prognostic value of TMEM45A has been recently reported in various types of human tumors, the association of TMEM45A expression and glioma is still unknown. Here, we reported that TMEM45A was significantly overexpressed in glioma tissues compared to non-tumorous brain tissues. Furthermore, TMEM45A mRNA levels were gradually increased with the increasing severity of histological grade of glioma. Moreover, high TMEM45A expression level was correlated with short survival time of glioma patients. Down-regulation of TMEM45A in two glioma cell lines, U251 and U373 by transected with TMEM45A siRNA resulted in a significant reduction of cell proliferation and G1-phase arrest. Additionally, we found that suppressing of TMEM45A expression in glioma cells remarkably suppressed cell migration and cell invasion. More importantly, TMEM45A siRNA treatment significantly down-regulated the proteins promoting cell cycles transition (Cyclin D1, CDK4 and PCNA) and cell invasion (MMP-2 and MMP-9), which indicted a possible mechanism underlying its functions on glioma. In summary, our study suggests that TMEM45A may work as an oncogene and a new effective therapeutic target for glioma treatment.
| S-EPMC4680400 | biostudies-literature
Project description:Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, which has the second highest incidence among gastrointestinal tumors. At present, due to the limitations of current CRC treatment strategies, there is an urgent need for developing more effective therapies. B7 family member H4 (B7-H4) is associated with the progression of a wide spectrum of cancers, but its functional role in CRC is unknown. The purpose of this study is to clarify the role of B7-H4 in CRC and the underlying mechanisms in controlling the progression of CRC. Our data showed that B7-H4 expression in CRC tissues and cell lines was significantly upregulated as compared with normal tissues and normal cell lines. High B7-H4 expression was correlated with a poor prognosis of CRC patients. B7-H4 overexpression promoted the proliferation and invasion of CRC cells, which could be suppressed by Wnt signaling inhibitor. In a mouse xenograft model, silencing B7-H4 suppressed tumor growth and epithelial-mesenchymal transition (EMT) of CRC cells. Collectively, our study demonstrated the oncogenic roles of B7-H4 in regulating the proliferation, EMT as well as the migration of CRC cells through Wnt signaling pathway. The heightened expression of B7-H4 could serve as a prognostic marker for CRC patients.
| S-EPMC8805878 | biostudies-literature
Project description:B cell-specific moloney murine leukemia virus integration site 1 (BMI1) is a transcriptional repressor of polycomb repressive complex 1, which is involved in the proliferation, senescence, migration, and tumorigenesis of cancer. Experimental researchers have convincingly linked BMI1 to tumorigenesis. However, there is no study about the issue on the role of BMI1 in the proliferation, apoptosis, and migration of bladder cancer. To address this question, we examined the expression of BMI1 in bladder cancer tissues and used siRNA to knockdown BMI1 expression in bladder cancer T24 cells. Then we tested the cell proliferation by CCK8 assay and soft agar colony formation assay, apoptosis by flow cytometry assay, and cell invasiveness by transwell migration assay. Our results revealed that BMI1 promoted proliferation, migration, invasion, and progression in bladder cancer. Over-expression of BMI1 was correlated with tumor clinic-pathological features. BMI1 siRNA effectively inhibited bladder cancer cell proliferation and migration in vitro, and it promoted bladder cancer invasion, maybe by causing epithelial-to-mesenchymal transition. Our findings suggested that BMI1 may represent a novel diagnostic marker and a therapeutic target for bladder cancer, and deserves further investigation.
| S-EPMC3771375 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Recent studies have demonstrated that SOX18 is highly expressed in various types of cancer. In the present study, we found that SOX18 mRNA was overexpressed in HCC compared with non-tumorous tissues. We aimed to explore the effects of SOX18 siRNA on the proliferation, invasion and migration of two HCC cell lines, MHCC97H and HepG2, which overexpress SOX18. We found that SOX18 siRNA significantly inhibited the proliferation and induced cell cycle arrest at the G0/G1 phase. Results of the Transwell assay showed that the migration and invasion of the HCC cells were markedly impaired in the SOX18-knockdown cells. Gene set enrichment analysis (GSEA) showed that KEGG focal adhesion and chemokine signaling pathways were correlated with SOX18 expression. Furthermore, the mRNA and protein levels of RhoA, PDGFB, IGF1R, CCL2, CCL3 and CCL5 were decreased in the SOX18-knockdown cells. Importantly, we demonstrated that upregulation of SOX18 was associated with a poor outcome in HCC patients. These results indicate that SOX18 may serve as a prognostic factor and a promising therapeutic strategy for HCC.
| S-EPMC4530902 | biostudies-literature
Project description:As a newly identified oncogenic long noncoding RNA (lncRNA), prostate cancer-associated transcript 6 (PCAT6) promoted cellular proliferation and colony formation of prostate cancer. However, the biological function of PCAT6 in lung cancer is still largely unknown. In this study, we found that PCAT6 is significantly increased in cancer tissues compared to normal tissues and positively correlates with metastasis of lung cancer in patients. We then examined PCAT6 expression in lung cancer cell lines and identified that PCAT6 expression was significantly elevated in lung cancer cells compared to normal human bronchial epithelial (NHBE) cells, especially in CL1-5 and H446 cells. PCAT6 knockdown significantly inhibited cellular proliferation and metastasis, as well as induced early apoptosis of lung cancer cells. Molecular analysis revealed that PCAT6 regulated the expression of two pivotal cancer-related proteins, c-Myc and p53, in lung cancer cells. However, PCAT6 was not directly combined with c-Myc and p53 as confirmed by RNA immunoprecipitation. Finally, a retrospective study further revealed that PCAT6 negatively correlates with overall survival of lung cancer patients. In conclusion, these results suggest that PCAT6 could play an oncogenic role in lung cancer progression and may serve as a biomarker for prognosis of lung cancer patients.
| S-EPMC7838661 | biostudies-literature
Project description:E2F3a, as a member of the E2F family, is essential for cell division associated with the progression of many cancers. However, the biological effect of E2F3a on glioma is not understood as well. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissue and cell lines. We found that E2F3a was upregulated in glioma tissue compared with adjacent tissue, and this was associated with a poor survival rate. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines. Knockdown of E2F3a significantly inhibited cell proliferation, promoted G0/G1 phase arrest, elevated apoptosis rates, and suppressed cell migration and invasion. However, overexpression of E2F3a markedly promoted cell proliferation, migration, and invasion and inhibited apoptosis. Moreover, in vivo studies showed that knockdown of E2F3a expression dramatically inhibited U373 tumor growth in a nude mouse model. Results of real-time PCR and Western blot showed that the depletion of E2F3a upregulated the expression levels of cell apoptosis-related proteins and downregulated migration-related proteins. Conversely, E2F3a overexpression downregulated the expression levels of cell apoptosis-related proteins and upregulated migration-related proteins. In conclusion, our results highlight the importance of E2F3a in glioma and provide new insights into the diagnostics and therapeutics of gliomas.
| S-EPMC7841128 | biostudies-literature
Project description:Thiol oxidation is a probable outcome of cellular oxidative stress and is linked to degenerative disease progression. In addition, protein thiol redox reactions are increasingly identified as a mechanism to regulate protein structure and function. We assessed the effect of hypothiocyanous acid on the cytoskeletal protein tubulin. Total cysteine oxidation by hypothiocyanous and hypochlorous acids was monitored by labeling tubulin with 5-iodoacetamidofluorescein and by detecting higher molecular weight inter-chain tubulin disulfides by Western blot under nonreducing conditions. Hypothiocyanous acid induced nearly stoichiometric oxidation of tubulin cysteines (1.9 mol cysteine/mol oxidant) and no methionine oxidation was observed. Because disulfide reducing agents restored all the polymerization activity that was lost due to oxidant treatment, we conclude that cysteine oxidation of tubulin inhibits microtubule polymerization. Hypothiocyanous acid oxidation of tubulin cysteines was markedly decreased in the presence of 4% glycerol, a component of the tubulin purification buffer. Due to its instability and buffer- and pH-dependent reactivity, hypothiocyanous acid studies require careful consideration of reaction conditions.
| S-EPMC3885989 | biostudies-literature
Project description:Colorectal cancer (CRC) is the third most common malignant tumor worldwide and is a serious threat to human health. MicroRNAs (miRNAs) play a key role in oncogenesis and cancer progression. MiRNA-125 (miR-125) is an important miRNA that is dysregulated in several kinds of cancers. Thus, we investigated the expression and effects of miR-125 and Transcriptional co-activator with PDZ-binding motif (TAZ) for a better understanding of the underlying mechanism of tumor progression in CRC, which may provide an emerging biomarker for diagnosis and treatment of CRC. We measured the expression levels of miR-125 in CRC tissues, adjacent tissues, and cell lines (e.g. HCT116, SW480, FHC) by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-125 on proliferation and invasion in CRC cells was detected by Cell Counting Kit-8 (CCK-8), clone formation assay, and transwell assay. Western blotting and qRT-PCR were used to investigate the expression of TAZ after knocking down miR-125 in HCT116 cells or overexpressing miR-125 in SW480 cells. MiR-125 was significantly down-regulated in CRC compared with pericarcinomatous tissue from 18 patients. An miR-125 inhibitor promoted CRC cell proliferation and invasion, while miR-125 mimic had the opposite effect. Moreover, we found that TAZ was an miR-125 target and the siRNA knockdown of TAZ could reverse the effect of the miR-125 inhibitor on proliferation and invasion in HCT116 cells. The present study shows that miR-125 suppresses CRC proliferation and invasion by targeting TAZ.
| S-EPMC6911154 | biostudies-literature
Project description:Expression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K-AKT-mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K-AKT-mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role in PCa via activation of the PI3K-AKT-mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa.
| S-EPMC7985494 | biostudies-literature
Project description:ObjectiveTo investigate the role of selenocysteine-tRNA specific eukaryotic elongation factor (EEFSEC) in regulating the proliferation, migration, and invasion of human prostate cancer 22Rv1 cells.MethodsWe detected EEFSEC mRNA expression levels in human normal prostate cell line RWPE1 and human prostate cancer cell lines 22Rv1, LNCaP, Vcap and PC-3 using qRT-PCR and EEFSEC protein expression in surgical specimens of prostate cancer and adjacent tissues using Western blotting. 22Rv1 cells were infected with a lentiviral vector carrying EEFSEC shRNA or a control lentivirus and the interference efficiency was determined using Western blotting. XTT assay was used to assess the changes in the viability of the infected cells, and Transwell chamber assay was used to examine the changes in cell migration and invasion. The effect of EEFSEC knockdown on cell cycle progression was determined with flow cytometry and by detecting the expressions of cell cycle proteins using qRT-PCR.ResultsEEFSEC was significantly upregulated in prostate cancer cells (P < 0.05), and a high expression of EEFSEC was associated with a poor prognosis of the patients with prostate cancer. In 22Rv1 cells, EEFSEC knockdown significantly suppressed the proliferation (P < 0.001), migration (P < 0.001) and invasion (P < 0.001) of the cells, resulted in cell cycle arrest in G0/G1 phase, obviously inhibited the expression of C-myc and CCNB1, and significantly increased the expression of p15.ConclusionEEFSEC knockdown can inhibit the proliferation, migration, and invasion of prostate cancer cells in vitro possibly by down-regulating the expression of C-myc.
| S-EPMC8752429 | biostudies-literature