scholarly journals Expression and prognosis of microliposome maintenance proteins family in liver cancer

2020 ◽  
Author(s):  
Xiao-Han Cui ◽  
Bei Zhu ◽  
Li Fu ◽  
Yuan-Xiang Lao ◽  
Chun-Fu Zhu ◽  
...  

Abstract Cancer is the leading cause of death worldwide, despite advances in the treatment of cancer, mortality of liver cancer remains high. The Microliposome maintenance (MCM) family has been reported to be involved in a variety of diseases. However, little is known about its expression and prognostic value in liver cancer. In this study, we analyzed the expression of the MCM family in liver cancer tissues and normal liver tissues. Oncomine and GEPIA were used to analyze the mRNA expression level of MCM family in liver cancer and other cancers. We observed that the mRNA expression levels of MCM1-8 and MCM10 are higher than normal tissues in most cancers. In addition, the expression levels of MCM1-10 were highly expressed in liver cancer cell lines, analyzed by Cancer Cell Line Encyclopedia (CCLE) and European Bioinformatics Institute (EMBL-EBI) databases. Furthermore, LinkedOmics and GEPIA databases were used to evaluate correlation between MCM1-10 and overall survival of patients. In the LinkedOmics-based survival analysis, high expressions of MCM2-8 and MCM10 were associated with worse patient prognosis (OS). The results showed that there was no correlation between the expression levels of MCM1 and MCM9 and prognosis of patients’ prognosis. The GEPIA dataset was also used for overall survival analysis, and the results also support the results of LinkedOmics.In conclusion, the MCM family has the potential to become a biomarker, especially MCM2-8 and MCM10 are probably the most promising biomarkers for liver cancer prognosis.

2021 ◽  
Vol 43 (3) ◽  
pp. 2199-2209
Author(s):  
Muhammed M. Salahuddin ◽  
Gamal A. Omran ◽  
Maged W. Helmy ◽  
Maha E. Houssen

Background: Breast cancer is the most common malignancy in women worldwide. P2X7 is a transmembrane receptor expressed in breast cancer and activated by the ATP tumor microenvironment, driving cell proliferation, angiogenesis, and metastasis via different signaling pathways. The role of the P2X7 receptor, hypoxia, and autophagy in regulating tumor progression is controversial. The multikinase inhibitor regorafenib prevents the activation of numerous kinases involved in angiogenesis, proliferation, and metastasis. The present study aimed to evaluate the modulatory effect of regorafenib on the hypoxia/angiogenesis/P2X7R/autophagy axis on the MCF7 breast cancer cell line and its impact on different signaling pathways involved in breast cancer pathogenesis. Methods: The levels of VEGF, VEGFR, PI3K, NF-κB, HIF-1α, and LC3-II were analyzed using ELISA, and caspase-3 activity was also assessed colorimetrically. Phosphorylated (p)-p38 MAPK and purinergic ligand-gated ion channel 7 (P2X7) receptor protein expression levels were analyzed via Western blotting. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of Beclin 1 (BECN1), LC3-II, and sequestosome 1 (p62). Results: Regorafenib reduced MCF7 cell viability in a dose-dependent manner. Furthermore, regorafenib significantly reduced levels of PI3K, NF-κB, VEGF, VEGFR, P2X7 receptor, and p-p38 MAPK protein expression, and markedly reduced p62 mRNA expression levels. However, regorafenib significantly increased caspase-3 activity, as well as BECN1 and LC3-II mRNA expression levels. Conclusions: Regorafenib was demonstrated to possibly exhibit antitumor activity on the breast cancer cell line via modulation of the P2X7/HIF-1α/VEGF, P2X7/P38, P2X7/ERK/NF-κB, and P2X7/beclin 1 pathways.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Radosław Januchowski ◽  
Piotr Zawierucha ◽  
Marcin Ruciński ◽  
Michał Nowicki ◽  
Maciej Zabel

Ovarian cancer is the leading cause of death among gynaecological malignancies. Extracellular matrix (ECM) can affect drug resistance by preventing the penetration of the drug into cancer cells and increased resistance to apoptosis. This study demonstrates alterations in the expression levels of ECM components and related genes in cisplatin-, doxorubicin-, topotecan-, and paclitaxel-resistant variants of the A2780 ovarian cancer cell line. Affymetrix Gene Chip Human Genome Array Strips were used for hybridisations. The genes that had altered expression levels in drug-resistant sublines were selected and filtered by scatter plots. The genes that were up- or downregulated more than fivefold were selected and listed. Among the investigated genes, 28 genes were upregulated, 10 genes were downregulated, and two genes were down- or upregulated depending on the cell line. Between upregulated genes 12 were upregulated very significantly—over 20-fold. These genes included COL1A2, COL12A1, COL21A1, LOX, TGFBI, LAMB1, EFEMP1, GPC3, SDC2, MGP, MMP3, and TIMP3. Four genes were very significantly downregulated: COL11A1, LAMA2, GPC6, and LUM. The expression profiles of investigated genes provide a preliminary insight into the relationship between drug resistance and the expression of ECM components. Identifying correlations between investigated genes and drug resistance will require further analysis.


2013 ◽  
Vol 28 (8) ◽  
pp. 579-587 ◽  
Author(s):  
Rongrong Zhu ◽  
Xianzheng Wu ◽  
Yu Xiao ◽  
Bo Gao ◽  
Qian Xie ◽  
...  

2017 ◽  
Vol 25 (4) ◽  
pp. 207-13 ◽  
Author(s):  
Paramita Paramita ◽  
Melva Louisa ◽  
Nafrialdi Nafrialdi

Background: Epithelial mesenchymal transition (EMT) plays a significant role in the development of cancer cell resistance to drugs. Vimentin, a type III intermediate filament protein, is a marker of EMT. Vimentin's over-expression in cancer correlates well with increased tumor growth, change in cell shape and poor prognosis. Endoxifen is an active metabolite of tamoxifen  and has become a new potent agent in the treatment of breast cancer. This is a study that aimed to investigate the effect of endoxifen exposure with or without estradiol on cell viability, cell morphology and EMT progression through the analysis of vimentin mRNA expression after 4-week treatment. Methods: Endoxifen, 100 nM or 1,000 nM, with or without beta-estradiol were given repeatedly to MCF-7 cells. Cells treated with dimethyl sulfoxide (DMSO) 0.001% were used as control. After 2- and 4-week exposure, the cells were counted, analyzed for mRNA vimentin expression, and observed for morphological changes. Results: Compared to control, there were significant decreases in vimentin mRNA expressions in endoxifen and endoxifen+β-estradiol treated cells after 2-weeks, which then significantly increased after 4-week compared with the 2-week exposure. We found no change in morphology of MCF-7 cells. Conclusion: Repeated exposure of endoxifen might induce EMT progression through increased expression of vimentin in MCF-7 breast cancer cell line.


2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.


Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 273 ◽  
Author(s):  
Stephanie Holst ◽  
Jennifer Wilding ◽  
Kamila Koprowska ◽  
Yoann Rombouts ◽  
Manfred Wuhrer

The caudal-related homeobox protein 1 (CDX1) is a transcription factor, which is important in the development, differentiation, and homeostasis of the gut. Although the involvement of CDX genes in the regulation of the expression levels of a few glycosyltransferases has been shown, associations between glycosylation phenotypes and CDX1 mRNA expression have hitherto not been well studied. Triggered by our previous study, we here characterized the N-glycomic phenotype of 16 colon cancer cell lines, selected for their differential CDX1 mRNA expression levels. We found that high CDX1 mRNA expression associated with a higher degree of multi-fucosylation on N-glycans, which is in line with our previous results and was supported by up-regulated gene expression of fucosyltransferases involved in antenna fucosylation. Interestingly, hepatocyte nuclear factors (HNF)4A and HNF1A were, among others, positively associated with high CDX1 mRNA expression and have been previously proven to regulate antenna fucosylation. Besides fucosylation, we found that high CDX1 mRNA expression in cancer cell lines also associated with low levels of sialylation and galactosylation and high levels of bisection on N-glycans. Altogether, our data highlight a possible role of CDX1 in altering the N-glycosylation of colorectal cancer cells, which is a hallmark of tumor development.


2020 ◽  
Vol 48 (12) ◽  
pp. 030006052093604
Author(s):  
Yi Jin ◽  
Tian-xi Wang ◽  
Hao Li ◽  
Peng Guo ◽  
Qing-qing Wang

Background Clear cell renal cell carcinoma (ccRCC) is a common urological disease. Expression of the protein tyrosine phosphatase 12 gene ( PTPN12) is decreased in many cancers; however, the relationship between PTPN12 gene function and renal cancer remains unclear. Methods We detected PTPN12 protein expression in ccRCC and corresponding normal tissues from 64 patients with ccRCC by immunohistochemistry, and relative PTPN12 mRNA levels by real-time quantitative polymerase chain reaction. The relationships between the relative expression levels of PTPN12 mRNA and the patients’ clinical data were analyzed. Results PTPN12 protein and mRNA expression levels were significantly lower in ccRCC compared with the corresponding normal tissues. The mRNA expression levels in the ccRCC and corresponding normal tissues from the 64 patients with ccRCC were 0.459±0.445 and 1.001±0.128, respectively, compared with the control (glyceraldehyde 3-phosphate dehydrogenase). There was a significant correlation between relative expression of PTPN12 mRNA in ccRCC tissues and tumor diameter and clinical stage. Conclusion The expression levels of PTPN12 protein and mRNA were significantly lower in ccRCC tissues compared with normal tissues. The role of PTPN12 may provide new insights and evidence to aid the diagnosis and targeted therapy of ccRCC.


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