High VRK1 expression contributes to cell proliferation and survival in hepatocellular carcinoma

Huang, Wei; Cui, Xiaopeng; Chen, Yuyan; Shao, Mengting; Shao, Xian; Shen, Yongjun; Liu, Qingqing; Wu, Miaomiao; Liu, Jinxia; Ni, Wenkai; Lu, Cuihua; Wan, Chunhua

doi:10.1016/j.prp.2015.11.015

Cited by 22 publications

(24 citation statements)

References 27 publications

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“…In addition, similarly to H2A T120ph blockade, suppression of VRK1 also could weaken the Ras-PI3K activationinduced increases of MG63 cell viability, proliferation and migration. These findings were consistent with the previous studies, which reported that knockdown of VRK1 reduced the proliferation and metastasis of breast cancer [16], oesophageal squamous cell carcinoma [41] and hepatocellular carcinoma [42]. Besides, we pointed out that Ras-PI3K activation elevated the VRK1 protein level in MG63 cells but had no significant effect on VRK1 mRNA level.…”

Section: Discussionsupporting

confidence: 93%

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Ras-PI3K pathway aberrant activation plays an important role in the occurrence and development of osteosarcoma. This study investigated the functions of Ras-PI3K pathway specific activation on histone H2A phosphorylation at threonine 120 (H2A T120ph) in osteosarcoma cells, along with the possible internal molecular mechanisms. Methods: Cell transfection was done to alter Ras G12V/Y40C , H2A T120ph and vaccinia-related kinase 1 (VRK1) expression. Then, cell viability, proliferation, migration and cell cycle distribution were assessed, respectively. qRT-PCR was utilized to measure the VRK1 and Ras-PI3K pathway downstream genes (CYR61, IGFBP3, WNT16B, NT5E, GDF15 and CARD16) expression. Chromatin immunoprecipitation (ChIP) was conducted to evaluate the input levels of H2A T120ph and VRK1 in the promoter regions of Ras-PI3K pathway downstream genes. Results: Ras-PI3K specific activation promoted histone H2A T120ph. H2A T120ph participated in the oncogenic functions of Ras-PI3K pathway on osteosarcoma by modulating the transcription of Ras-PI3K-targeted genes. Moreover, VRK1 contributed to the Ras-PI3K specific activation-induced up-regulation of H2A T120ph and osteosarcoma progression. Ras-PI3K pathway-specific activation-induced up-regulation of H2A T120ph was achieved by up-regulation of VRK1. Conclusions: Ras-PI3K pathway activation promoted osteosarcoma progression might be via up-regulating VRK1-mediated H2A T120ph. We proposed that VRK1 and H2A T120ph could be the potential targets for osteosarcoma diagnosis and treatment. HIGHLIGHTS 1. H2A T120ph is specifically promoted by Ras-PI3K pathway activation. 2. H2A T120ph joins in the oncogenic effects of Ras-PI3K pathway on osteosarcoma. 3. H2A T120ph regulates the transcription of Ras-PI3K-targeted genes. 4. VRK1 takes part in the regulatory function of Ras-PI3K pathway on H2A T120ph .

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Section: Discussionsupporting

confidence: 93%

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…Moreover, VRK1 elimination by CRISPR/Cas9 identifies wild-type VRK1 as an overexpressed oncogenic driver gene [ 114 ], consistent with its role in lung adenocarcinomas [ 115 ]. In most cell types, the human VRK1 gene is expressed at different levels and is not mutated in cancer, and it is overexpressed in many cancer types of different origins correlating with a poorer prognosis in breast [ 116 , 117 ], lung [ 115 ], liver [ 118 ], glioblastoma [ 119 ], head and neck [ 110 ], and esophageal cancer [ 120 ]. Some driver genes are oncogenic in situations in which they are overexpressed by different mechanisms, as it occurs with members of the MYC and EGFR families that promote cell proliferation.…”

Section: Implications Of Vrk1 In Cancer Biologymentioning

confidence: 99%

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

Campillo-Marcos

Lazo

2018

Cell. Mol. Life Sci.

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DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage.

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“…Human hepatoma cell line HepG2 (Catalog Number: SCSP-510) was purchased from Cell bank of Chinese Academy of Sciences (Shanghai, China). Human hepatic cell line (L02) and human hepatoma cell line (Huh7) were obtained from Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University [14]. All the cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM, Gibco, USA) which was supplemented with 10% of fetal bovine serum (FBS).…”

Section: Cell Lines and Transfectionmentioning

confidence: 99%

Selenoprotein P inhibits cell proliferation and ROX production in HCC cells

et al. 2020

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Selenoprotein P (SEPP1) is a kind of secretory glycoproteins with an antioxidant effect during the development of some diseases. In this study, we attempted to observe the expression of SEPP1 in livers from the patients with hepatocellular carcinoma (HCC) and explore its effect on HCC cells. All the tissues from patients with HCC were obtained from Affiliated Hospital of Nantong University. Western blot and immunohistochemical results showed that SEPP1 was reduced in HCC liver tissues. Its expression was negatively correlated with Ki67 expression in tissues. The expression of SEPP1 in normal liver cell line was significantly higher than those in the liver cancer cell lines. Serum starvation and release experiment demonstrated that SEPP1 expression was reduced and PCNA expression was increased, when the serum was re-added into cell culture system and the cells were on a proliferation state. After SEPP1 over-expression plasmid was transfected into HepG2 cells, cell proliferation of HepG2 cells and PCNA expression level were all inhibited by SEPP1. Results obtained via 8-isoprostane ELISA further indicated that inhibited ROS level was found in HepG2 cells transfected with SEPP1 over-expression plasmid. In addition, RT-qPCR results demonstrated that GPX1 expression levels increased in HepG2 cells transfected with SEPP1 over-expression plasmid. In conclusion, SEPP1 may inhibit the proliferation of HCC cells, accompanied by the reduction of ROS production and the increasing of GPX1 expression.

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High VRK1 expression contributes to cell proliferation and survival in hepatocellular carcinoma

Cited by 22 publications

References 27 publications

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

Selenoprotein P inhibits cell proliferation and ROX production in HCC cells

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