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Gene network exploration of crosstalk between apoptosis and autophagy in chronic myelogenous leukemia.

Wang F, Cho WC, Chan LW, Wong SC, Tsui NB, Siu PM, Yip SP, Yung BY - Biomed Res Int (2015)

Bottom Line: Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus.The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks.The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Technology and Informatics, Hong Kong Polytechnic University, Lee Shau Kee Building, Hung Hom, Kowloon, Hong Kong.

ABSTRACT

Background: Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear.

Results: Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks.

Conclusion: The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.

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Related in: MedlinePlus

Cumulative distribution functions of coexpression levels for the normal and the CML groups with the candidate thresholds from 0 to 1.
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fig1: Cumulative distribution functions of coexpression levels for the normal and the CML groups with the candidate thresholds from 0 to 1.

Mentions: Among 20 genes considered in this work (see Table S1 in Supplementary Material available online at http://dx.doi.org/10.1155/2015/459840), the coexpression levels of 190 gene pairs were computed for the normal group and the CML group independently. Gene pairs can be dichotomized into strong and weak coexpression classes, which characterized the corresponding groups. The threshold for the dichotomy was determined by two-sample KS test. The CDFs for the normal and the CML groups were numerically evaluated at every possible threshold value from 0 to 1 (Figure 1). It was found that the evaluated cumulative fractions were optimally deviated by D, 0.2789, at the coexpression level C, 0.4233 (optimal threshold). The KS test indicated that the two distributions were significantly different (P value < 0.01 for the statistic D = 0.2789). The contingency table of the gene pair counts at the optimal threshold is shown in Table 2. At the optimal threshold, the dichotomy of gene pairs was significantly associated with the disease as the Chi-square statistic was 31.4957 (P value < 0.01). The differential coexpression distribution suggested that the genes related to apoptosis and autophagy, in overall, exhibited more robust functional links in the normal group than the CML group.


Gene network exploration of crosstalk between apoptosis and autophagy in chronic myelogenous leukemia.

Wang F, Cho WC, Chan LW, Wong SC, Tsui NB, Siu PM, Yip SP, Yung BY - Biomed Res Int (2015)

Cumulative distribution functions of coexpression levels for the normal and the CML groups with the candidate thresholds from 0 to 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4363532&req=5

fig1: Cumulative distribution functions of coexpression levels for the normal and the CML groups with the candidate thresholds from 0 to 1.
Mentions: Among 20 genes considered in this work (see Table S1 in Supplementary Material available online at http://dx.doi.org/10.1155/2015/459840), the coexpression levels of 190 gene pairs were computed for the normal group and the CML group independently. Gene pairs can be dichotomized into strong and weak coexpression classes, which characterized the corresponding groups. The threshold for the dichotomy was determined by two-sample KS test. The CDFs for the normal and the CML groups were numerically evaluated at every possible threshold value from 0 to 1 (Figure 1). It was found that the evaluated cumulative fractions were optimally deviated by D, 0.2789, at the coexpression level C, 0.4233 (optimal threshold). The KS test indicated that the two distributions were significantly different (P value < 0.01 for the statistic D = 0.2789). The contingency table of the gene pair counts at the optimal threshold is shown in Table 2. At the optimal threshold, the dichotomy of gene pairs was significantly associated with the disease as the Chi-square statistic was 31.4957 (P value < 0.01). The differential coexpression distribution suggested that the genes related to apoptosis and autophagy, in overall, exhibited more robust functional links in the normal group than the CML group.

Bottom Line: Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus.The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks.The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Technology and Informatics, Hong Kong Polytechnic University, Lee Shau Kee Building, Hung Hom, Kowloon, Hong Kong.

ABSTRACT

Background: Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear.

Results: Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks.

Conclusion: The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.

Show MeSH
Related in: MedlinePlus