Silencing GTSE-1 expression inhibits proliferation and invasion of hepatocellular carcinoma cells

Guo, Lei; Zhang, Shumin; Zhang, Bo; Chen, Wanyong; Li, Xiaoqiang; Zhang, Wentao; Zhou, Chixing; Zhang, Jubo; Ren, Ning; Ye, Qing–Hai

doi:10.1007/s10565-016-9327-z

Cited by 37 publications

(34 citation statements)

References 23 publications

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“…GTSE1 regulates the cell cycle by interacting with p53 and repressing its ability to induce apoptosis . Previous studies have investigated the expression and functional mechanisms of GTSE1 with respect to the tumor cell cycle . Consistently, our investigation showed that upregulation of GTSE1 leads to increased G2/M phase in AMC‐1 cells, and GTSE1 depletion decreased G2/M phase in WM2664 cells.…”

Section: Discussionsupporting

confidence: 81%

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

Chen

et al. 2018

Cancer Science

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G2 and S‐phase expressed 1 (GTSE1) regulates cell cycle progression in human cancers. However, its significance and mechanism of action in acral melanoma (AM) remain unknown. In the present study, we found that GTSE1 expression was upregulated in advanced stage/metastatic AM tissues and metastatic cell lines, and correlated with higher stage (P = .028) and poor disease‐free survival (DFS) in patients with AM (P = .003). Cox regression assays validated GTSE1 expression to be an independent prognostic factor of DFS for patients with AM (P = .004). Ectopic expression of GTSE1 enhanced primary AM cell proliferation, invasion, and migration. Loss‐of‐function in GTSE1 attenuated metastatic AM cell proliferation and metastatic ability in vitro and in vivo. We additionally observed that inhibition of migration and invasion occurred concomitantly with a GTSE1 knockdown‐mediated increase in E‐cadherin and decreases in N‐cadherin and Slug. We further showed that integrin subunit alpha 2 (ITGA2) interacts with GTSE1 and is a downstream effector of GTSE1. Further, ITGA2 levels were positively correlated with GTSE1 expression in human AM tissues. Ectopic ITGA2 expression rescued siGTSE1‐mediated inhibition of migration and invasion, thereby restoring epithelial‐to‐mesenchymal transition (EMT). In conclusion, GTSE1 expression promotes AM progression and correlates with clinical outcomes of patients with AM, and may represent a promising therapeutic target to suppress AM progression.

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Section: Discussionsupporting

confidence: 81%

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

Chen

et al. 2018

Cancer Science

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“…GTSE1 has been demonstrated as a potential biomarker for poor clinical outcome in several types of cancer [10,13,27]. Previous research suggested GTSE1's functional role in hepatocellular carcinoma (HCC) proliferation, colony formation, invasion, and overall survival [9,13]. In our study, DEGs in GTSE1 knockdown In addition to GTSE1, overexpression of CDC20, PCNA, and MCM has been detected in many types of human cancer [28][29][30].…”

Section: Discussionmentioning

confidence: 64%

“…While in normal condition, GTSE1 is activated by functional p53 binding on the GTSE1 promoter region and encodes GTSE1 protein to cause a delay from G2 to M transition [3,8]. Recent studies revealed that overexpression of GTSE1 contributes to promoting cell proliferation, migration, and invasion in different cancers via translocalizing p53 to the cytoplasm [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…High expression of GTSE1 was associated with short overall survival of patients suffering breast cancer, bladder cancer, and/or liver cancer [9][10][11][12][13]. Also, elevated GTSE1 significantly interferes with chemotherapy efficacy and influences the survival probability of patients with hepatocellular carcinoma (HCC) [9,13]. However, the underlying mechanism of how GTSE1 interacts with other cell cycle-related genes to influence prognosis in liver cancer is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

Zheng

Shi

et al. 2019

Analytical Cellular Pathology

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GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.

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“…It also responds to DNA damage and inhibits apoptosis. GTSE1 inhibition significantly decreased tumor growth in vitro and in vivo, and suppressed migration and invasion in vitro [18]. Our co-staining data of GTSE1 and Ki67 revealed that fibrotic regions showed high expression of Ki67 accompanied with GTSE1 overexpression in 90Gy focal irradiated lung tissues (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 87%

Identification of molecular signatures involved in radiation-induced lung fibrosis

et al. 2018

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In radiotherapy, radiation (IR)-induced lung fibrosis has severe and dose-limiting side effects. To elucidate the molecular effects of IR fibrosis, we examined the fibrosis process in irradiated mouse lung tissues. High focal IR (90 Gy) was exposed to a 3-mm volume of the left lung in C57BL6 mice. In the diffused irradiation, 20 Gy dose delivered with a 7-mm collimator almost covered the entire left lung. Histological examination for lung tissues of both irradiated and neighboring regions was done for 4 weeks after irradiation. Long-term effects (12 months) of 20Gy IR were compared on a diffuse region of the left lung and non-irradiated right lung. Fibrosis was initiated as early as 2 weeks after IR in the irradiated lung region and neighboring region. Upregulation of gtse1 in both 90Gy-irradiated and neighboring regions was observed. Upregulation of fgl1 in both 20Gy diffused irradiated and non-irradiated lungs was identified. When gtse1 or flg1 was knock-downed, TGFβ or IR-induced epithelial-mesenchymal transition was inhibited, accompanied with the inhibition of cellular migration, suggesting fibrosis responsible genes. Immunofluorescence analysis using mouse fibrotic lung tissues suggested that fibrotic regions showed increased expressions of Gtse1 and Fgl1, indicating novel molecular signatures of gtse1and fgl1 for IR-induced lung fibrosis. Even though their molecular mechanisms and IR doses or irradiated volumes for lung fibrosis may be different, these genes may be novel targets for understanding IR-induced lung fibrosis and in treatment strategies.Key messages Upregulation of gtse1 by 90Gy focal irradiation and upregulation of fgl1 by 20Gy diffused irradiation are identified in mouse lung fibrosis model.Gtse1 and Fgl1 are involved in radiation or TGFβ-induced epithelial-mesenchymal transition.Radiation-induced fibrotic regions of mouse lungs showed increased expressions of Gtse1 and Fgl1.Gtse1 and Fgl1 are suggested to be novel targets for radiation-induced lung fibrosis. Electronic supplementary materialThe online version of this article (10.1007/s00109-018-1715-9) contains supplementary material, which is available to authorized users.

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Silencing GTSE-1 expression inhibits proliferation and invasion of hepatocellular carcinoma cells

Cited by 37 publications

References 23 publications

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

Identification of molecular signatures involved in radiation-induced lung fibrosis

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