Dataset Information

Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.

ABSTRACT:

Background

Cancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells.

Methods

Western blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells. Overexpression and knockdown assays were used to examine the effects of TRIM28 on the expression of MAGEC2 protein. Immunohistochemistry (IHC) staining was performed in hepatocellular carcinoma patients to evaluate the association between the expression of MAGEC2 and TRIM28. Proteasome inhibitors MG132 or PS-341 and lysosome inhibitor Chloroquine (CQ) were used to inhibit proteasomal or lysosomal-mediated protein degradation respectively.

Results

We demonstrate that MAGEC2 interacts with TRIM28 in melanoma cells and MAGEC2 expression in tumor cells depends on the expression of TRIM28. The expression level of MAGEC2 protein was significantly reduced when TRIM28 was depleted in tumor cells, and no changes were observed in MAGEC2 mRNA level. Furthermore, expression levels of MAGEC2 and TRIM28 are positively correlated in MAGEC2-positive human hepatocellular carcinoma tissues (p?=?0.0011). Mechanistic studies indicate that the regulatory role of TRIM28 on MAGEC2 protein expression in tumor cells depends on proteasome-mediated pathway.

Conclusions

Our findings show that TRIM28 is necessary for MAGEC2 expression in cancer cells, and TRIM28 may serve as a new potential target for immunotherapy of cancer.

SUBMITTER: Song X

PROVIDER: S-EPMC6182782 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.

Song Xiao X Guo Chengli C Zheng Yutian Y Wang Ying Y Jin Zhongtian Z Yin Yanhui Y

BMC cancer 20181011 1

<h4>Background</h4>Cancer/testis antigen MAGEC2 (also known as HCA587) is highly expressed in a wide variety of tumors and plays an active role in promoting growth and metastasis of tumor cells. However, little is known for the regulation of MAGEC2 expression in cancer cells.<h4>Methods</h4>Western blotting and quantitative RT-PCR were performed to analyze MAGEC2 expression. Co-immunoprecipitation assay was applied for detecting the endogenous interaction of MAGEC2 and TRIM28 in tumor cells. Ove ...[more]

PMID: 30309319

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Project description:BackgroundDue to their restricted expression in male germ cells and certain tumors, cancer/testis (CT) antigens are regarded as promising targets for tumor therapy. CT45 is a recently identified nuclear CT antigen that was associated with a severe disease score in Hodgkin's lymphoma and poor prognosis in multiple myeloma. As for many CT antigens, the biological function of CT45 in developing germ cells and in tumor cells is largely unknown.MethodsCT45 expression was down-regulated in CT45-positive Hodgkin's lymphoma (L428), fibrosarcoma (HT1080) and myeloma (U266B1) cells using RNA interference. An efficient CT45 knock-down was confirmed by immunofluorescence staining and/or Western blotting. These cellular systems allowed us to analyze the impact of CT45 down-regulation on proliferation, cell cycle progression, morphology, adhesion, migration and invasive capacity of tumor cells.ResultsReduced levels of CT45 did not coincide with changes in cell cycle progression or proliferation. However, we observed alterations in cell adherence, morphology and migration/invasion after CT45 down-regulation. Significant changes in the distribution of cytoskeleton-associated proteins were detected by confocal imaging. Changes in cell adherence were recorded in real-time using the xCelligence system with control and siRNA-treated cells. Altered migratory and invasive capacity of CT45 siRNA-treated cells were visualized in 3D migration and invasion assays. Moreover, we found that CT45 down-regulation altered the level of the heterogeneous nuclear ribonucleoprotein syncrip (hnRNP-Q1) which is known to be involved in the control of focal adhesion formation and cell motility.ConclusionsProviding first evidence of a cell biological function of CT45, we suggest that this cancer/testis antigen is involved in the modulation of cell morphology, cell adherence and cell motility. Enhanced motility and/or invasiveness of CT45-positive cells could contribute to the more severe disease progression that is correlated to CT45-positivity in several malignancies.

Dataset Information

Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.

Background

Methods

Results

Conclusions

Publications

Post-transcriptional regulation of cancer/testis antigen MAGEC2 expression by TRIM28 in tumor cells.

Similar Datasets

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