A novel regulatory event-based gene set analysis method for exploring global functional changes in heterogeneous genomic data sets

Tung, Chien Yi; Jen, Chih Hung; Hsu, Ming; Wang, Hsei Wei; Lin, Chi

doi:10.1186/1471-2164-10-26

Cited by 11 publications

(6 citation statements)

References 34 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, this study showed that TCD triggered the ER stress-signaling pathway in both Mahlavu and Hep-J5 cells. Our finding is in accordance with several earlier reports that processes involving microtubule-based action and cytoskeletal organization are important biological functions in HCC [ 32 , 33 ].…”

Section: Discussionsupporting

confidence: 94%

A Novel Microtubule-Disrupting Agent Induces Endoplasmic Reticular Stress-Mediated Cell Death in Human Hepatocellular Carcinoma Cells

Chang

Yang

et al. 2015

PLoS ONE

View full text Add to dashboard Cite

Here, we present evidence of a novel microtubule-disrupting agent, N-deacetyl-N-(chromone-2-carbonyl)-thiocolchicine (TCD), exhibiting potent antitumor activity (with IC50 values in the nanomolar range) against hepatocellular carcinoma cell lines. Cell cycle analysis revealed that TCD induced G2/M cell-cycle arrest in a dose- and time-dependent manner in both Hep-J5 and Mahlavu HCC cell lines. TCD also induced a decrease in mitochondrial membrane potential (ΔΨm) and caused DNA damage. Mechanistically, TCD activated protein kinase RNA-like endoplasmic reticular kinase and several transcription factors, including activating transcription factor (ATF) 6, ATF4, ATF3, and the CCAAT-enhancer binding protein homologous protein. These data clearly demonstrate that the antitumor activity of TCD is mechanistically linked to its capacity to trigger both intrinsic and extrinsic apoptotic cell death via endoplasmic reticular stress pathway. The potent antitumor activity of TCD was similarly demonstrated in a hepatocellular carcinoma xenograft model, where 5 and 10 mg/kg doses of TCD significantly arrested Hep-J5 and Mahlavu tumor growth. Our finding suggests that TCD is a promising therapeutic agent against hepatocellular carcinoma; further translational assessment of its clinical usage is warranted.

show abstract

Section: Discussionsupporting

confidence: 94%

A Novel Microtubule-Disrupting Agent Induces Endoplasmic Reticular Stress-Mediated Cell Death in Human Hepatocellular Carcinoma Cells

Chang

Yang

et al. 2015

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Using this approach, we found that the cellular assembly and organization through the microtubule functional networks ranked the most significant cellular event in HCC. Our finding is consistent with several earlier reports on expression profiling of HCC, which also suggested the microtubule-based processes and microtubule cytoskeletal organization to be important biological and cellular components in HCC (29,30). In line with our finding, other profiling studies also found the microtubule regulatory gene STMN1 to be commonly upregulated in HCC (31,32).…”

Section: Discussionsupporting

confidence: 83%

Novel therapeutic potential in targeting microtubules by nanoparticle albumin-bound paclitaxel in hepatocellular carcinoma

et al. 2011

View full text Add to dashboard Cite

Abstract. Hepatocellular carcinoma (HCC) shows low response to most conventional chemotherapies. To facilitate target identification for novel therapeutic development, we deployed gene expression profiling on 43 paired HCC tumors and adjacent non-tumoral liver, which is also considered as the pre-malignant liver lesion. In conjunction with ontology analysis, a major functional process found to play a role in the malignant transformation of HCC was microtubule-related cellular assembly. We further examined the potential use of microtubule targeting taxane drugs, including paclitaxel and docetaxel, and compared with findings to results from doxorubicin, a common chemotherapeutic agent used in HCC. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, the nanoparticle albumin-bound (nab)-paclitaxel was also examined. In a panel of HCC cell lines studied, a high sensitivity towards taxane drugs was generally found, although the effect from nab-paclitaxel was most profound. The nabpaclitaxel showed an effective IC 50 dose at 15-fold lower than paclitaxel alone or the derivative analogue docetaxel, and 450-fold less compared to doxorubicin. Flow cytometric analysis confirmed a cell cycle blockade at the G 2 /M phase and increased apoptosis following nab-paclitaxel treatment.In vivo animal studies also showed that nab-paclitaxel readily inhibited xenograft growth with less toxicity to host cells compared to other anti-microtubule drugs and doxorubicin. Gene silencing of the microtubule regulatory gene STMN1 by RNAi suggested a distinct synergistic effect in the combined treatment with nab-paclitaxel. Our findings in this study highly suggest that the microtubule assembly represents a promising therapeutic target development in HCC.

show abstract

“…The whole set of MMT-dependent transcriptomes (both of the up-and downregulated DEGs) was submitted for analysis, which considers all the consistently changed genes and every gene regulation of each sample to avoid the detection limit. 33 Interestingly, a unique Src-centric network that contains most of the MMT-associated DEGs resulted. We further demonstrated the involvement of Src in MMT, as its mRNA expression level was increased in the TGF-b1-stimulated BMDMs from 3 hours onward.…”

Section: Discussionmentioning

confidence: 99%

The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring

Tang

Zhou

et al. 2018

Kidney International

100

124

View full text Add to dashboard Cite

A novel regulatory event-based gene set analysis method for exploring global functional changes in heterogeneous genomic data sets

Cited by 11 publications

References 34 publications

A Novel Microtubule-Disrupting Agent Induces Endoplasmic Reticular Stress-Mediated Cell Death in Human Hepatocellular Carcinoma Cells

A Novel Microtubule-Disrupting Agent Induces Endoplasmic Reticular Stress-Mediated Cell Death in Human Hepatocellular Carcinoma Cells

Novel therapeutic potential in targeting microtubules by nanoparticle albumin-bound paclitaxel in hepatocellular carcinoma

The proto-oncogene tyrosine protein kinase Src is essential for macrophage-myofibroblast transition during renal scarring

Contact Info

Product

Resources

About