Excavating the pathogenic gene of breast cancer based on high throughput data of tumor and somatic reprogramming

Cell Cycle ◽  
2021 ◽  
pp. 1-15
Author(s):  
Lian Duan ◽  
Zhendong Wang ◽  
Xin Zheng ◽  
Junjian Li ◽  
Huamin Yin ◽  
...  
2019 ◽  
Author(s):  
Yun Zhang ◽  
Gautam Bandyopadhyay ◽  
David J. Topham ◽  
Ann R. Falsey ◽  
Xing Qiu

AbstractBackgroundFor many practical hypothesis testing (H-T) applications, the data are correlated and/or with heterogeneous variance structure. The regressiont-test for weighted linear mixed-effects regression (LMER) is a legitimate choice because it accounts for complex covariance structure; however, high computational costs and occasional convergence issues make it impractical for analyzing high-throughput data. In this paper, we propose computationally efficient parametric and semiparametric tests based on a set of specialized matrix techniques dubbed as the PB-transformation. The PB-transformation has two advantages: 1. The PB-transformed data will have a scalar variance-covariance matrix. 2. The original H-T problem will be reduced to an equivalent one-sample H-T problem. The transformed problem can then be approached by either the one-sample Studentst-test or Wilcoxon signed rank test.ResultsIn simulation studies, the proposed methods outperform commonly used alternative methods under both normal and double exponential distributions. In particular, the PB-transformedt-test produces notably better results than the weighted LMER test, especially in the high correlation case, using only a small fraction of computational cost (3 versus 933 seconds). We apply these two methods to a set of RNA-seq gene expression data collected in a breast cancer study. Pathway analyses show that the PB-transformedt-test reveals more biologically relevant findings in relation to breast cancer than the weighted LMER test․.ConclusionsAs fast and numerically stable replacements for the weighted LMER test, the PB-transformed tests are especially suitable for “messy” high-throughput data that include both independent and matched/repeated samples. By using our method, the practitioners no longer have to choose between using partial data (applying paired tests to only the matched samples) or ignoring the correlation in the data (applying two sample tests to data with some correlated samples).


2021 ◽  
Vol 11 ◽  
Author(s):  
Huayao Li ◽  
Chundi Gao ◽  
Qing Liang ◽  
Cun Liu ◽  
Lijuan Liu ◽  
...  

Background: Resistance to endocrine therapy has hampered clinical treatment in patients with ER-positive breast cancer (BRCA). Studies have confirmed that cryptotanshinone (CPT) has cytotoxic effects on BRCA cells and can significantly inhibit the proliferation and metastasis of ER-positive cancer cells.Methods: We analyzed the gene high-throughput data of ER-positive and negative BRCA to screen out key gene targets for ER-positive BRCA. Finally, the effects of CPT on BRCA cells (MCF-7 and MDA-MB-231) were examined, and quantitative RT-PCR was used to evaluate the expression of the key targets during CPT intervention.Results: A total of 169 differentially expressed genes were identified, and revealed that CPT affects the ER-positive BRCA cells by regulating CDK1, CCNA2, and ESR1. The overall experimental results initially show that MCF-7 cells were more sensitive to CPT than MDA-MB-231 cells, and the expression of ESR1 was not affected in the BRCA cells during CPT intervention, while the expression of CDK1 and CCNA2 were significantly down-regulated.Conclusion: CPT can inhibit the proliferation and migration of BRCA cells by regulating CDK1, CCNA2, and ESR1, especially in ER-positive BRCA samples. On the one hand, our research has discovered the possible mechanism that CPT can better interfere with ER+ BRCA; on the other hand, the combination of high-throughput data analysis and network pharmacology provides valuable information for identifying the mechanism of drug intervention in the disease.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Débora Ferreira ◽  
Joaquim Barbosa ◽  
Diana A. Sousa ◽  
Cátia Silva ◽  
Luís D. R. Melo ◽  
...  

AbstractTriple-negative breast cancer is the most aggressive subtype of invasive breast cancer with a poor prognosis and no approved targeted therapy. Hence, the identification of new and specific ligands is essential to develop novel targeted therapies. In this study, we aimed to identify new aptamers that bind to highly metastatic breast cancer MDA-MB-231 cells using the cell-SELEX technology aided by high throughput sequencing. After 8 cycles of selection, the aptamer pool was sequenced and the 25 most frequent sequences were aligned for homology within their variable core region, plotted according to their free energy and the key nucleotides possibly involved in the target binding site were analyzed. Two aptamer candidates, Apt1 and Apt2, binding specifically to the target cells with $$K_{d}$$ K d values of 44.3 ± 13.3 nM and 17.7 ± 2.7 nM, respectively, were further validated. The binding analysis clearly showed their specificity to MDA-MB-231 cells and suggested the targeting of cell surface receptors. Additionally, Apt2 revealed no toxicity in vitro and showed potential translational application due to its affinity to breast cancer tissue sections. Overall, the results suggest that Apt2 is a promising candidate to be used in triple-negative breast cancer treatment and/or diagnosis.


Author(s):  
Yongjoo Kim ◽  
Jongeun Lee ◽  
A. Shrivastava ◽  
J. W. Yoon ◽  
Doosan Cho ◽  
...  

Amino Acids ◽  
2008 ◽  
Vol 35 (3) ◽  
pp. 517-530 ◽  
Author(s):  
Xing-Ming Zhao ◽  
Luonan Chen ◽  
Kazuyuki Aihara

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