Dataset Information

STK33 promotes hepatocellular carcinoma through binding to c-Myc.

ABSTRACT:

Objective

STK33 has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in hepatocellular carcinoma (HCC) and its underlying mechanisms.

Design

251 patients with HCC were analysed for association between STK33 expression and clinical stage and survival rate. Tamoxifen (TAM)-inducible, hepatocyte-specific STK33 transgenic and knockout mice models were used to study the role of STK33 in liver tumorigenesis. HCC cell lines were used to study the role of STK33 in cell proliferation in vitro and in vivo.

Results

STK33 expression was found to be frequently upregulated in patients with HCC. Significant associations were found between increased expression of STK33 and advanced HCC staging and shorter disease-free survival of patients. Overexpression of STK33 increased HCC cell proliferation both in vitro and in vivo, whereas suppression of STK33 inhibited this effect. Using a TAM-inducible, hepatocyte-specific STK33 transgenic mouse model, we found that overexpression of STK33 resulted in increased hepatocyte proliferation, leading to tumour cell burst. Using a TAM-inducible, hepatocyte-specific STK33 knockout mouse model, we found that, when subjected to the diethylnitrosamine (DEN) liver cancer bioassay, STK33KO(flox/flox, Alb-ERT2-Cre) mice exhibited a markedly lower incidence of tumour formation compared with control mice. The underlying mechanism may be that STK33 binds directly to c-Myc and increases its transcriptional activity. In particular, the C-terminus of STK33 blocks STK33/c-Myc association, downregulates HCC cell proliferation, and reduces DEN-induced liver tumour cell number and tumour size.

Conclusions

STK33 plays an essential role in hepatocellular proliferation and liver tumorigenesis. The C-terminus of STK33 could be a potential therapeutic target in the treatment of patients with STK33-overexpressed HCC.

SUBMITTER: Yang T

PROVIDER: S-EPMC4717356 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

STK33 promotes hepatocellular carcinoma through binding to c-Myc.

Yang Tian T Song Bin B Zhang Jin J Yang Guang-Shun GS Zhang Han H Yu Wei-Feng WF Wu Meng-Chao MC Lu Jun-Hua JH Shen Feng F

Gut 20141114 1

<h4>Objective</h4>STK33 has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in hepatocellular carcinoma (HCC) and its underlying mechanisms.<h4>Design</h4>251 patients with HCC were analysed for association between STK33 expression and clinical stage and survival rate. Tamoxifen (TAM)-inducible, hepatocyte-specific STK33 transgenic and knockout mice models were used to study the role of STK33 in liver tumorigenesis. HCC cell lines were used ...[more]

PMID: 25398772

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Project description:PurposeThe purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression.MethodsQuantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments.ResultsIn this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression.ConclusionsHsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.

Dataset Information

STK33 promotes hepatocellular carcinoma through binding to c-Myc.

Objective

Design

Results

Conclusions

Publications

STK33 promotes hepatocellular carcinoma through binding to c-Myc.

Similar Datasets

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