Effect of PAK1 gene silencing on proliferation and apoptosis in hepatocellular carcinoma cell lines MHCC97-H and HepG2 and cells in xenograft tumor

Zhang, Zhilei; Liu, Guangchao; Peng, Li; Zhang, Chong; Jia, Yuming; Yang, Wuhan; Mao, Lei

doi:10.1038/s41434-018-0016-9

Cited by 23 publications

(12 citation statements)

References 23 publications

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“…In short, these results suggested that besides regulating PI3K/AKT and NF-κB pathway, knockdown of PAK1 could also regulate proliferation by inactivating MAPK pathway. Previous study demonstrated that PAK1 gene silencing might decrease proliferation and increase apoptosis of hepatocellular carcinoma cells by regulating the p53/p21 pathway [35]. In this study, we showed that knockdown of PAK1 increased the expressions of p53 and p21, and decreased the expressions of CyclinD1, MDM2 and CDK4.…”

Section: Discussionsupporting

confidence: 53%

Effect of p21-activated kinase 1 inhibition on proliferation, migration and invasion of glioma

Yi¹,

Chen²,

Zhou³

et al. 2020

Preprint

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Background: Abnormally expressed the p21-activated kinases (PAKs) are implicated in the development and treatment of glioma. Previous study has reported that PAK1 is expressed in glioma. However, the role and mechanism of PAK1 in glioma progression remain unclear.Methods: Western blotting was employed to detect the expression of PAK1 in human glioma tissues. CCK-8, EdU and colony formation assay were applied to evaluate the effect of PAK1 inhibition on cell proliferation of glioma. The flow cytometry was utilized to examine the cell cycle distribution and apoptotic rate of glioma. Wound healing and transwell assay were exploited to investigate the effect of PAK1 inhibition on cell migration and invasion of glioma. The orthotopic xenograft glioma model was established to probe the effect of PAK1 silencing on tumor formation of U87 cell. Results: It was showed that PAK1 was significantly upregulated in glioma tissues. Besides, high level of PAK1 was found to be associated with poor prognosis in glioma patients in TCGA database. PAK1 inhibition restrained cell proliferation, arrested cells at G1 phase, and induced cell apoptosis of glioma. PAK1 inhibition suppressed glioma cell migration and invasion. Moreover, knockdown of PAK1 dramatically decreased the protein expressions including MDM2, p38, p-p38, CyclinD1, CDK4, Bcl-2, MMP2, MMP9, Cofilin, while increased the protein levels of p53, Bax, p21 and Cleaved Caspase-3. Finally, orthotopic xenograft glioma model confirmed that silencing of PAK1 repressed the tumor formation of U87 cell transplantation.Conclusion: Our study described that PAK1 inhibition impedes proliferation, migration and invasion of glioma cells and thus probably as a novel target for glioma therapy.

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Section: Discussionsupporting

confidence: 53%

Effect of p21-activated kinase 1 inhibition on proliferation, migration and invasion of glioma

Yi¹,

Chen²,

Zhou³

et al. 2020

Preprint

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“…33) From in vivo study, silencing of Pak1 gene decreases proliferation in xenograft tumor through the p53/p21 pathway. 34) In the present study, Pak1 was proved to be the target gene of miR-665. Interestingly, Pak1 promotes the proliferation and inhibits apoptosis via the Akt pathway.…”

Section: Discussionmentioning

confidence: 52%

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

et al. 2020

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Myocardial infarction (MI) is one of the major causes of death worldwide, and the therapeutic strategies of MI are still limited. In this study, we investigated the function of miR-665 in MI. In the present study, an ischemia/reperfusion (I/R) rat model and a hypoxia/reoxygenation (H/R)-induced H9c2 cell model were successfully established to mimic the MI for in vivo and in vitro studies. The concentrations of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α), IL-6, and reactive oxygen species (ROS) were then measured. Moreover, cell viability and apoptosis were detected by MTT assay, TdT-mediated dUTP nick end labeling (TUNEL), and PI/FITC-annexin V assay. The binding of miR-665 and Pak1 was determined by luciferase assay. miR-665 was upregulated in I/R rats, and the overexpression of miR-665 significantly increased LDH, CK-MB, TNF-α, IL-6, and ROS concentrations and induced cell apoptosis, while knockdown of miR-665 had opposite results. Consistent with in vivo results, miR-665 induced cell apoptosis and ROS generation in H/R-treated H9c2 cells. More importantly, Pak1 was the target gene of miR-665, and knockdown of miR-665 depressed the accumulation of ROS and cell apoptosis by targeting Pak1 and promoting the phosphorylation of Akt, whereas knockdown of Pak1 could attenuate the protection of miR-665 inhibitor in H/ R-treated H9c2 cells. Therefore, knockdown of miR-665 protects against cardiomyocyte ischemia/reperfusion injury-induced ROS accumulation and apoptosis through activating Pak1/Akt signaling in MI. In general, understanding the biology and modulation of miR-665 may have the potential to counteract the development of MI.

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“…Genistein downregulated the expression of AURKA and AURKB. PAK1 silencing has been shown to decrease cell proliferation [49]. High PAK1 expression in cervical cancer is associated with its pathological features including angiogenesis, upregulation of MMP2, metastasis and poor prognosis [50,51].…”

Section: Discussionmentioning

confidence: 99%

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

Sundaram

Unni

Somvanshi

et al. 2019

Genes

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Background: Several epigenetic changes are responsible for transcriptional alterations of signaling pathways and tumour suppressor genes (TSGs) contributing to carcinogenesis. This study was aimed to examine the effect of the phytochemical, genistein on various molecular targets in HeLa cells. Methods: Quantitative PCR was used to analyze the expression of various molecular targets. Biochemical assays were employed to study the epigenetic enzymes. To correlate the transcriptional status of the selected TSGs and epigenetic modulation, their promoter 5'CpG methylation levels were evaluated by quantitative methylation array followed by methylation specific restriction digestion. Results: The expression of several genes involved in the cell cycle regulation, migration, inflammation, phosphatidylinositol 3-kinase (PI3K) and mitogen activated kinase-like protein (MAPK) pathway were found to be modulated including CCNB1, TWIST1, MMP14, TERT, AKT1, PTPRR, FOS and IL1A. Genistein modulated the expression of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), demethylases, and histone phosphorylases. Furthermore, genistein decreased the activity of DNMTs, HDACs, and HMTs and reduced global DNA methylation levels. Promoter methylation of several TSGs, including FHIT, RUNX3, CDH1, PTEN, and SOC51, was lowered with corresponding transcriptional increase. Network analysis indicated similar effect of genistein. Conclusion: This study presents a comprehensive mechanism of action of genistein showcasing effective epigenetic modulation and widespread transcriptional changes resulting in restoration of tumour suppressor gene expression. This study corroborates the development of genistein as a candidate for anti-cancer therapy.

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Effect of PAK1 gene silencing on proliferation and apoptosis in hepatocellular carcinoma cell lines MHCC97-H and HepG2 and cells in xenograft tumor

Cited by 23 publications

References 23 publications

Effect of p21-activated kinase 1 inhibition on proliferation, migration and invasion of glioma

Effect of p21-activated kinase 1 inhibition on proliferation, migration and invasion of glioma

Knockdown of miR-665 Protects Against Cardiomyocyte Ischemia/Reperfusion Injury-Induced ROS Accumulation and Apoptosis Through the Activation of Pak1/Akt Signaling in Myocardial Infarction

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

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