In Vivo and In Vitro Effects of Tracheloside on Colorectal Cancer Cell Proliferation and Metastasis.
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ABSTRACT:
SUBMITTER: Shin MK
PROVIDER: S-EPMC8064450 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposePrevious studies have reported that the levels of PRDX2 were correlated with tumorigenicity, recurrence, and prognosis of patients with different cancers. We investigated the association between PRDX2 levels and the prognosis of lung cancer patients. We also measured PRDX2 expression of non-small cell lung cancer (NSCLC) cells and examined its roles in the proliferation and migration in vitro and in vivo.MethodsWe used the Kaplan-Meier plotter to analyze the survival of different levels of PRDX2 in lung cancer patients. The expression of PRDX2 in normal bronchial epithelial cell line and NSCLC cell lines was measured by qRT-PCR and western blot assays. Biological functions of NSCLC cells were detected by CCK8 and Transwell assays. We constructed tumor growth model using subcutaneously injection of nude mice and metastasis model by tail vein injection in vivo. The protein levels of proliferation related markers were measured by immunohistochemistry assay. Immunofluorescence method was used to detected EMT-related proteins.ResultsThe high levels of PRDX2 were associated with bad prognosis in lung cancer patients, especially in patients with adenocarcinoma. The expression of PRDX2 in NSCLC cell lines was higher than normal bronchial epithelial cells. Knockdown of PRDX2 inhibited the proliferation, migration, and invasion in A549 cells, while overexpression of PRDX2 promoted the malignancy in NCI-H1299 cells in vitro. Silencing PRDX2 restrained tumor growth and repressed lung metastasis by EMT in vivo.ConclusionOur data indicates that PRDX2 functions as a protumor regulator and is involved in tumorigenesis and tumor progression of lung cancer.
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Project description:Emerging evidence indicates that the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is associated with tumourigenesis in various types of cancer. However, its specific effects on the proliferation, invasion and metastasis of colorectal cancer (CRC) are still poorly understood. The present study aimed to investigate PVT1 expression in CRC and explore its role in CRC pathogenesis. The reverse transcriptase?quantitative polymerase chain reaction (RT?qPCR) technique was used to assess PVT1 expression in CRC cell lines. Gene Expression Omnibus (GEO) database analysis and measurement of clinical samples was used to analyse the correlation between PVT1 expression, CRC metastasis and overall survival (OS). In addition, knockdown of PVT1 expression was performed using short interfering RNA (siRNA) and RT?qPCR, western blotting, CCK?8 assays, tumour cell clone?formation and Matrigel invasion assays were used to observe its biological functions in HCT116 cells. The present study demonstrated that the expression of PVT1 in CRC cell lines was higher than that in normal colon mucosal cell lines. Using GEO database analysis and the measurement of clinical samples, it was revealed that CRC patients with high PVT1 expression demonstrated poor OS. Multivariate analysis indicated that high PVT1 expression is an independent risk factor for patients with CRC. In addition, PVT1 knockdown suppressed the proliferation, invasion and metastasis of CRC cells in vitro, which were associated with decreasing vimentin, cyclin D1 and cyclin?dependent kinase 4 expression and enhanced E?cadherin expression. The results of the present study suggest that PVT1 may serve a critical role in CRC progression and metastasis and may serve as a potential prognostic biomarker for CRC.
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Project description:Background:Dysregulation of long non-coding RNAs (lncRNAs) is closely related with the progression of cancer in humans. The functional and regulatory roles of lncRNAs in colorectal cancer (CRC) are still largely unclear. The purpose of this study is to explore the function of lncRNA STARD13-AS in CRC. Methods:The bioinformatics tool "GEPIA" was used to predict the potential expression of STARD13-AS in CRC. qRT-PCR was used to evaluate the relative expression level of STARD13-AS in CRC cells lines and tissues samples. The functional involvement of STARD13-AS in the CRC cells was assessed using MTT assay, ?ow cytometry, and Transwell assay. The expression levels of cyclin D, cyclin E, E-cadherin, N-cadherin, and vimentin were assessed using Western blot. Results:Bioinformatics prediction and qRT-PCR results showed that STARD13-AS expression was decreased in CRC tissues. Patients with low STARD13-AS expression exhibited distant and lymphatic metastasis as well as enhancement in tumor size. STARD13-AS expression was downregulated in CRC cell lines compared to normal human colon mucosal epithelial cell line NCM460 and STARD13-AS expression in SW620 and LoVo cell lines was lowest. Moreover, we observed that while STARD13-AS overexpression suppressed the cell cycle, proliferation, migration, and invasion, while promoted apoptosis both in LoVo and SW620 cells. In addition, STARD13-AS overexpression inhibited Cyclin E, Cyclin D, N-cadherin and vimentin expression, and promoted E-cadherin expression both in LoVo and SW620 cells. Conclusion:Expression of STARD13-AS suppresses cell proliferation and metastasis in CRC, suggesting that STARD13-AS might act as a potential target for CRC treatment.
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Project description:BackgroundWe have recently reported an inverse relationship between colon cancer progression and tumour proliferative activity. Here, we extend our findings by evaluating the proliferative activity of liver metastatic lesions and primary colorectal cancers (CRC) that differ in their metastatic potential.MethodsUsing an earlier established multi-gene proliferation signature (GPS), proliferative levels were analysed in 73 primary CRCs and 27 liver metastases.ResultsCompared with primary CRCs, we observed a significantly lower expression of the GPS in liver metastases and confirmed their lower proliferative levels by quantitative RT-PCR and Ki-67 immunostaining. No difference could be detected in apoptotic indices as assessed by M30 immunostaining, indicating that the net growth rate is lower in metastases relative to primary tumours. Notably, relapsed primaries or those with established metastases had significantly lower proliferative activity than CRCs that were non-metastatic and did not relapse.ConclusionOur results suggest that slow proliferation is a biological characteristic of both liver metastases and those primary tumours with the ability to metastasise. The delineation of the mechanisms underlying the inverse association between proliferation and CRC aggressiveness may be important for the development of new therapeutic strategies.
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Project description:BackgroundFeminization-1 (FEM-1) is considered a substrate recognition subunit of CUL2-RING E3 ubiquitin ligase complexes, which refers to sex determination by modulating TRA-1 stability in C. elegans. The function of mammalian orthologous gene of FEM-1 remains to be elucidated.MethodsThe expression of FEM1C in colorectal cancer (CRC) cells was interfered by small interference RNA (siRNA) transfection, and Cell counting kit-8 (CCK-8) assay, colony formation assay and transwell assay were performed. In order to estimate the function on metastasis, stable knockdown FEM1C cells were used to established liver and lung metastasis models. In addition, the expression of FEM1C in normal tissues, adenomas and tumor tissues were analyzed, and the relationship between FEM1C expression level and prognosis was analyzed by Kaplan-Meier method.ResultsHere, we report that the elimination of FEM1C, one of the members of FEM-1, significantly promoted the migration and invasion of colorectal cancer (CRC) cells in vitro and promoted liver and lung metastases in vivo. It also showed that the removal of FEM1C improved the proliferation ability of CRC cells. In particular, the cell shape changed from epithelial to fibroblast-like morphology. The tight cell monolayer was transformed into a dispersed distribution. Furthermore, it was demonstrated that FEM1C is down-regulated in tissues of CRC compared to normal tissues, and the high expression of FEM1C positively correlates with a good prognosis in patients with CRC. GSEA analysis showed that EMT signatures was enriched in FEM1C knockdown groups.ConclusionsDown-regulation of FEM1C promotes proliferation and metastasis, and FEM1C may be a tumor suppressor in the development of CRC.
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