Overexpression of myocyte enhancer factor 2 and histone hyperacetylation in hepatocellular carcinoma

Bai, Xueli; Wu, Lianfeng; Liang, Tingbo; Liu, Zhiqiang; Li, Junjian; Li, Donglin; Xie, Haiyang; Yin, Shengyong; Yu, Jun; Qiu, Lin; Zheng, Shusen

doi:10.1007/s00432-007-0252-7

Cited by 79 publications

(57 citation statements)

References 45 publications

(51 reference statements)

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“…In prostate and ovarian tumors, decrease of H3K9ac has been linked with tumor progression. In fact, the H3K9ac expression level correlates with histological grading and the clinical stage (Bai et al, 2008;Mohamed et al, 2007;Zhen et al, 2010). In agreement, a decrease in H3K9ac is coupled with a poor prognosis for these patients (Seligson et al, 2005;Zhen et al, 2010).…”

Section: Acetylation/trimethylation Of H3k9mentioning

confidence: 60%

“…In agreement, a decrease in H3K9ac is coupled with a poor prognosis for these patients (Seligson et al, 2005;Zhen et al, 2010). In contrast, in hepatocellular carcinoma an increase in H3K9ac levels was reported (Bai et al, 2008). The decrease of H3K9Ac is required for the increase of H3K9me3, and similar to the acetylation status of H3K9, its methylation status has also been linked to cancer.…”

Section: Acetylation/trimethylation Of H3k9mentioning

confidence: 75%

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Histone onco-modifications

2011

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Post-translational modification of histones provides an important regulatory platform for processes such as gene expression, DNA replication and repair, chromosome condensation and segregation and apoptosis. Disruption of these processes has been linked to the multistep process of carcinogenesis. We review the aberrant covalent histone modifications observed in cancer, and discuss how these epigenetic changes, caused by alterations in histonemodifying enzymes, can contribute to the development of a variety of human cancers. As a conclusion, a new terminology 'histone onco-modifications' is proposed to describe post-translational modifications of histones, which have been linked to cancer. This new term would take into account the active contribution and importance of these histone modifications in the development and progression of cancer.

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Section: Acetylation/trimethylation Of H3k9mentioning

confidence: 60%

Section: Acetylation/trimethylation Of H3k9mentioning

confidence: 75%

Histone onco-modifications

2011

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“…FOXM1 is a potential therapeutic target in mature B cell tumors [49] and ATF2 has been recently found to be highly disregulated in lymphoma [50]. Besides BCL6 discussed above, the N/D list for DLBC contains genes (MEF2A [51], NCOA1 [52], TGIF1 [53], NFATC3 [54]) that are all known to have a functional role in cancer, even if they have not been associated to the specific Bcell cancer types we have considered. Our predictions are for the immortalized cell lines we have selected, some of which are commonly used for in-vitro testing in many laboratories.…”

Section: Discussionmentioning

confidence: 99%

“…MAP3K3 and MAP3K14 are in the MAPK/ERK pathway which is a target of many novel therapeutic agents [44], and SRC is a well known oncogene and a candidate target in lung cancer [45]. BCL6 (B-cell lymphoma 6) is the most common oncogene in DLBCL, and it is known that its excell tumors [49] and ATF2 has be highly disregulated in lympho discussed above, the N/D list fo (MEF2A [51], NCOA1 [52], TG that are all known to have a fu even if they have not been assoc Table! We! have!…”

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confidence: 99%

Attractor Signaling Models for Discovery of Combinatorial Therapies

Piermarocchi¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE 2. REPORT TYPE Annual DATES COVERED (From -To) TITLE AND SUBTITLEAttractor ignaling odels for iscovery of mbinatorial herapies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER AUTHOR(S)Carlo Piermarocchi 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Michigan State University AND ADDRESS(ES) Easy PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) SPONSOR/MONITOR'S ACRONYM(S) SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release SUPPLEMENTARY NOTES ABSTRACTThe objective of this project consists in demonstrating that attractor models increase the chances of discovering combinations of many drugs with strong synergistic effects in lung cancer. The approach will be tested using a high throughput screening facility to compare the therapeutic effectiveness of random combinations and combinations predicted to be effective by the model. !Drug-based!therapies!are!therefore!the! best!option,!but!intrinsic!and!acquired!drug!resistance!still!makes!the!5-year!survival!rate!for!this!disease! less!than!15%.!Over!the!years,!many!specific!mechanisms!associated!with!drug!resistance!in!lung!cancer! have! been! pinpointed,! but! we! are! still! far! from! understanding! how! to! overcome! it. Combination! drug! therapy!is!commonly!used!to!enhance!efficacy!and!overcome!drug!resistance!in!cancer,!but!at!present! the! choice! of! drugs! and! doses! is! based! on! empirical! clinical! experience! alone.! In! this! project! we! have! used! an! interdisciplinary! approach! based! on! the! mathematics! of! complex! networks! to! identify! drug! combinations!that!could!be!effective!in!the!therapy!of!lung!cancer.!! ! This! reports! describes! the! methods! used! and! presents! some! preliminary! computational! and! experimental! data! that! we! have! obtained! during! the! first! year! of! operations.! The! project! has! been! extended!to!August!14!2014!and!additional!details!and!data!will!be!included!in!the!final!report.! ! ! ! where!! !" !is!the!adjacency!matrix!of!the!lu...

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“…The sustained histone acetylation might in turn lead to transcriptional deregulation, which would partly explain why cirrhosis often results in hepatoma. 48,49 To prove directly that a small part of the liver can function as an intact one, we established a 70% PH mouse model in which liver regeneration was severely deprived by retrorsine pretreatment. Retrorsine is a well- .…”

Section: Discussionmentioning

confidence: 99%

Activation of Inactive Hepatocytes through Histone Acetylation

Shi

Sun

Bao

et al. 2011

The American Journal of Pathology

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The mechanisms by which hepatic function is maintained after extensive parenchymal loss are unclear. In this study, we propose a novel concept of "functional heterogeneity" of hepatocytes based on their different expression of acetylated histones, the markers of active gene transcription, to explain the powerful compensatory capability of the liver. In the healthy human liver, only a fraction of the hepatocytes were marked by acetylated histones (ac-H2AK5, ac-H2BK5, ac-H3K9, ac-H3K14, ac-H3K27, and ac-H3K9/14). With the progression of cirrhosis, the ratio of the positive cells was gradually elevated, accompanied by the gradual exhaustion of the negative cells. By examining the global transcriptome of the mouse hepatocytes, we observed that the primed genes in the positive cells were much more numerous than those in negative cells. In a 70% hepatectomized mouse, the remnant hepatocytes were extensively activated, and the liver function was well maintained even when regeneration was severely inhibited. The functional compensation was absolutely dependent on the elevated expression of acetyl-histones. Additionally, when liver regeneration was blocked, the metabolism-related genes seemed to be preferentially transcribed. In conclusion, we demonstrate that normally, part of the active hepatocytes are competent for routine physiological requirements. The inactive hepatocytes, delicately regulated by acetyl-histones, act as a functional reservoir for future activation to restore the liver func- The liver has a unique regenerative capacity that restores its mass and function after diverse injuries, including a 70% to 95% partial hepatectomy (PH) in rodents and humans, by the proliferation of differentiated hepatocytes.1-3 Liver regeneration is commonly considered to be the adaptive process by which liver structure and function are recovered. However, in some cases, rodents can survive for an extended period of time after a 70% PH even when liver regeneration is chemically disrupted. 4 -6 Similarly, despite the on-going decrement of hepatocytes, patients suffering from chronic cirrhosis can keep their liver function normal for many years. [7][8][9] This evidence suggests that the remnant liver can compensate for the initial loss of hepatic function independent of cell mass recovery. The powerful compensatory capability of the liver raises an interesting question: why does the body need so many hepatocytes when a minority of the liver mass seems competent? We hypothesize that only a subset of hepatocytes is functionally active at any given time, or each individual hepatocyte is only partially active. The subset of the inactive or the incompletely activated hepatocytes, therefore, acts as a functional reservoir that can be invoked for functional compensation. Molecular

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Overexpression of myocyte enhancer factor 2 and histone hyperacetylation in hepatocellular carcinoma

Abstract: These data showed a potential molecular mechanism that activated HSCs participate in the pathogenesis of HCCs by overexpression of MEF2 and its consequent impact on histone hyperacetylation. Further investigations aimed at interfering MEF2 expression are needed.

Cited by 79 publications

References 45 publications

Histone onco-modifications

Histone onco-modifications

Attractor Signaling Models for Discovery of Combinatorial Therapies

Activation of Inactive Hepatocytes through Histone Acetylation

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