Histone acetyltransferase PCAF Up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling

Zheng, Xin; Gai, Xiaowu; Ding, Feihu; Lu, Zhongxin; Tu, Kangsheng; Yao, Yingmin; Liu, Qingguang

doi:10.1186/1476-4598-12-96

Cited by 41 publications

(47 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An Annexin v-FLUOS Staining kit (Roche) was used to determine the level of cell apoptosis, according to the manufacturer's protocols. The caspase 3/7 activity assay was performed using an Apo-ONE ® Homogeneous Caspase-3/7 Assay (Promega, WI, USA), as described in a previous study (24).…”

Section: Quantitative Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

“…Multiple studies found that AKT signaling pathway is aberrantly hyperactivated in HCC, which results in the promotion of tumor progression (6,24). Furthermore, it has been reported that AKT signaling plays a key role in facilitating MMP2 and MMP9 expression (6).…”

Section: Overall Survival Ratementioning

confidence: 99%

“…Disease-free survival rate Previously, activated AKT signaling has been considered to facilitate tumor cell proliferation, invasion and migration (24). Multiple studies found that AKT signaling pathway is aberrantly hyperactivated in HCC, which results in the promotion of tumor progression (6,24).…”

Section: Overall Survival Ratementioning

confidence: 99%

“…Extensive research indicates that WWOX is downregulated in various tumor types including HCC (19)(20)(21)(22) (23). The AKT signaling pathway, is critical in promoting cell proliferation, invasion and migration, and is frequently dysregulated in multiply tumor types (24). Furthermore, it has been reported that AKT signaling plays a key role in facilitating MMP2 and MMP9 expression, which are important factors in the progression of HCC (25).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling

Xie

Zen

Wang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Several studies have revealed that ACK1 is upregulated in various cancers and promotes tumor progression. However, the role and mechanism of ACK1 in hepatocellular carcinoma (HCC) remains unknown. In this study, the expression of ACK1 was assessed in several cell lines and 150 pairs of HCC and adjacent noncancerous liver tissues. The protein expression of p-ACK1 and WWOX were detected by immunohistochemistry to evaluate their correlation with ACK1. Flow cytometry, caspase 3/7 activity assay, BrdU cell proliferation assay, MTT assay and Transwell assay were used to detect apoptosis, proliferation, invasion and migration of HCC cells. The regulatory effect of ACK1 on WWOX, AKT, p-AKT, MMP2 and MMP9 in HCC cells was confirmed by immuno blotting. We found that ACK1 was more highly expressed in HCC tissues than in non-HCC tissues, and over expression of ACK1 was correlated with clinicopathological features of poor prognosis. Clinical analysis demonstrated that ACK1 is an independent prognostic marker for predicting overall survival and disease-free survival of HCC patients. Pearson's correlation coefficient analysis indicated that ACK1 was positively associated with p-ACK1 and was negatively associated with WWOX expression. In vitro studies showed that knockdown of ACK1 promoted HCC cell apoptosis and repressed HCC cells invasion, migration and proliferation. Furthermore, knockdown of ACK1 resulted in upregulation of WWOX and inactivation of AKT signaling. In this study, we also found that knockdown of ACK1 resulted in the downregulation of MMP2 and MMP9 in HCC. Our results indicate that ACK1 is an independent prognostic marker and promotes HCC progression via downregulating WWOX and activating AKT signaling.

show abstract

Section: Quantitative Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

Section: Overall Survival Ratementioning

confidence: 99%

Section: Overall Survival Ratementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling

Xie

Zen

Wang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Formalin-fixed, paraffin-embedded tumor samples were collected for the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The TUNEL assay was used to evaluate cell apoptosis in the xenograft tissues as described previously [13]. All in vivo experiment protocols were approved by the Institutional Animal Care and Use Committee of the First Affiliated Hospital of Xi'an Jiaotong University.…”

Section: Methodsmentioning

confidence: 99%

MACC1 Suppresses Cell Apoptosis in Hepatocellular Carcinoma by Targeting the HGF/c-MET/AKT Pathway

Yao

Dou

et al. 2015

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background & Aims: To investigate the expression and prognostic value of MACC1 in patients with HCC and identify the mechanism by which MACC1 inhibits HCC cell apoptosis. Methods: MACC1 and p-AKT expression was studied using immunohistochemistry of both HCC tissues and adjacent liver tissues. qRT-PCR and western immunoblotting were used to examine the expression of target genes at the mRNA and protein levels, respectively. The MTT assay was used to assess cell viability, and cell apoptosis was determined by DAPI staining, Annexin V/PI staining and Caspase 3/7 assay. Nude mice were used to perform in vivo experiments. Results: The overexpression of MACC1 was found in HCC tissues and was correlated with poor postsurgical prognosis. There was a positive relationship between MACC1 and p-AKT expression in HCC tissues. In vitro experiments showed that MACC1 repressed HCC cell apoptosis and promoted cell growth. Knockdown of c-MET abolished the anti-apoptotic function of MACC1. Next, MACC1 was verified to activate PI3K/AKT signaling by sensitizing HGF/c-MET signaling in HCC. MACC1 overexpression enhanced the HGF-driven phosphorylation of BAD, Caspase 9 and FKHRL1 and inhibited their pro-apoptotic functions in HCC cells. Finally, MACC1 was shown to inhibit cell apoptosis and promote HCC growth in vivo. Conclusions: This investigation revealed that MACC1 overexpression predicted worse prognosis after liver resection, which was attributed to the repression of HCC cell apoptosis via a molecular mechanism in which MACC1 accelerated the activation of the HGF/c-MET/PI3K/AKT pathway and phosphorylated BAD, Caspase 9 and FKHRL1, ultimately preventing their nuclear translocation and their pro-apoptotic function.

show abstract

Retracted: TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer

Tian

Liu

Guo

et al. 2018

J of Cellular Biochemistry

View full text Add to dashboard Cite

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2-1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase-3, Bax and Bcl-2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl-2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase-3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC.

show abstract

Histone acetyltransferase PCAF Up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling

Cited by 41 publications

References 33 publications

ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling

ACK1 promotes hepatocellular carcinoma progression via downregulating WWOX and activating AKT signaling

MACC1 Suppresses Cell Apoptosis in Hepatocellular Carcinoma by Targeting the HGF/c-MET/AKT Pathway

Retracted: TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer

Contact Info

Product

Resources

About