GINS Complex Subunit 2 Facilitates Gastric Adenocarcinoma Proliferation and Indicates Poor Prognosis

Huang, Feng; Zeng, Juntao; Gao, Lei; Zhou, Zhen; Wang, Liya

doi:10.1620/tjem.255.111

Cited by 6 publications

(6 citation statements)

References 32 publications

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“…The results show that GINS2 expression is increased in most tumors compared to normal tissues and correlates with various clinicopathological features. It has been demonstrated that GINS2 is expressed at higher levels in tumor tissue than in adjacent normal tissue, such as in CC[ 3 ], gastric adenocarcinoma[ 6 ], glioma[ 7 ], NSCLC[ 8 , 9 ], pancreatic cancer[ 10 , 11 ], and thyroid cancer (TC)[ 12 , 13 ]. Specifically, analysis of potential correlations between GINS2 expression levels and clinicopathological features has indicated that high GINS2 expression levels are closely associated with tumor size[ 6 , 10 ], tumor nodal metastasis (TNM) stage[ 6 , 8 ], pathological grade[ 7 ] and vascular permeation[ 10 ].…”

Section: Expression Profiles Of Gins2 In Cancersmentioning

confidence: 99%

“…GINS2, also known as Psf2, is located in regions 2 and 4 of the long arm of chromosome 16 with a length of 1196 bp[ 2 ], as shown in Figure 1 . Recent results suggest that GINS2 expression is upregulated in many diseases, especially tumors, and adversely affects prognosis, such as in patients with cervical cancer (CC)[ 3 ], breast cancer (BC)[ 4 , 5 ], gastric adenocarcinoma[ 6 ], glioma[ 7 ], non-small cell lung cancer (NSCLC)[ 8 , 9 ], and pancreatic cancer[ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Shan¹,

Zheng²,

Chen³

2022

World J Gastrointest Oncol

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Cancer incidence and mortality are increasing globally, leading to its rising status as a leading cause of death. The Go-Ichi-Ni-San (GINS) complex plays a crucial role in DNA replication and the cell cycle. The GINS complex consists of four subunits encoded by the GINS1, GINS2, GINS3, and GINS4 genes. Recent findings have shown that GINS2 expression is upregulated in many diseases, particularly tumors. For example, increased GINS2 expression has been found in cervical cancer, gastric adenocarcinoma, glioma, non-small cell lung cancer, and pancreatic cancer. It correlates with the clinicopathological characteristics of the tumors. In addition, high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration, inhibiting tumor cell apoptosis, and blocking the cell cycle. This review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor development. GINS2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.

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Section: Expression Profiles Of Gins2 In Cancersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Shan¹,

Zheng²,

Chen³

2022

World J Gastrointest Oncol

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“…The TCGA database analysis revealed that all members of GINS were upregulated in LUAD tissues and their high expression predicted the prognosis of the patients. Several studies demonstrated that the expression of a GINS member enhanced cancer cell aggressiveness, e.g., proliferation, drug resistance, and epithelial-mesenchymal transition [55,59,60]. Therefore, GINS members are closely involved with LUAD pathogenesis and may be potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

Tomioka

Shioiri

Seki

et al. 2023

Cells

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The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downregulated in LUAD tissues. Ectopic expression of both miRNAs induced cell cycle arrest in LUAD cells, suggesting both strands of miRNAs derived from pre-miR-486 were tumor suppressive. Our in silico analysis showed a total of 99 genes may be under the control of both miRNAs in LUAD cells. Importantly, among these targets, the high expression of seven genes (MKI67, GINS4, RRM2, HELLS, MELK, TIMELESS, and SAPCD2) predicted a poorer prognosis of LUAD patients (p < 0.05). We focused on GINS4, a DNA replication complex GINS protein that plays an essential role in the initiation of DNA replication. Our functional assays showed that GINS4 was directly controlled by both strands of pre-miR-486, and its aberrant expression facilitated the aggressive behavior of LUAD cells. GINS4 is attractive as a therapeutic target for this disease. MiRNA analysis, including passenger strands, will further improve our understanding of the molecular pathogenesis of LUAD.

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“…Among all gastric cancer cases, the majority of patients were diagnosed as stomach adenocarcinoma (STAD) arising from malignant change of gastric gland cells, accounting for 90–95% of total cases [ 2 ]. The causative factors of STAD are commonly attributed to environmental stimuli (mainly H. pylori infection) and genetic susceptibility [ 3 ]. Despite the availability of multidisciplinary combination therapy including surgery and chemotherapy for STAD patients in the past decades, clinical outcomes remain suboptimal and median survival time has not been effectively prolonged [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

METTL3 regulates N6-methyladenosine modification of ANGPTL3 mRNA and potentiates malignant progression of stomach adenocarcinoma

Zhang

et al. 2023

BMC Gastroenterol

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Background N6-methyladenosine (m6A) is associated with mammalian mRNA biogenesis, decay, translation and metabolism, and also contributes greatly to gastrointestinal tumor formation and development. Therefore, the specific mechanisms and signaling pathways mediated by methyltransferase-like 3 (METTL3), which catalyzes the formation of m6A chemical labeling in stomach adenocarcinoma (STAD), are still worth exploring. Methods Quantitative real-time PCR (qRT-PCR) was constructed to detect the expression of METTL3 in gastric cancer cell lines and patient tissues. The biological function of METTL3 was investigated in vitro/in vivo by Cell Counting Kit-8, colony formation assay, Transwell assay and nude mouse tumorigenesis assay. Based on the LinkedOmics database, the genes co-expressed with METTL3 in the TCGA STAD cohort were analyzed to clarify the downstream targets of METTL3. Methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) and RNA stability analysis were employed to explore the mechanism of METTL3 in gastric cancer progression. Results We analyzed TCGA data and found that METTL3 was frequently elevated in STAD, and demonstrated that METTL3 was present at high levels in clinical STAD tissues and cells. High METTL3 expression was more likely to have advanced TNM tumors and distant metastasis. On the other hand, METTL3 silencing effectively impeded the higher oncogenic capacity of AGS and HGC27 cells in vivo and in vitro, as reflected by slowed cell growth and diminished migration and invasion capacities. Continued mining of the TCGA dataset identified the co-expression of angiopoietin-like 3 (ANGPTL3) and METTL3 in STAD. Lower level of ANGPTL3 was related to increased level of METTL3 in STAD samples and shorter survival times in STAD patients. ANGPTL3 enrichment limited the growth and metastasis of STAD cells. Besides, ANGPTL3 mRNA levels could be decreased by METTL3-dominated m6A modifications, a result derived from a combination of MeRIP-qPCR and RNA half-life experiments. Importantly, the inhibitory effect of METTL3 silencing on cancer could be reversed to some extent by ANGPTL3 inhibition. Conclusions Overall, our findings suggested that METTL3 functioned an oncogenic role in STAD by reducing ANGPTL3 expression in an m6A-dependent manner. The discovery of the METTL3-ANGPTL3 axis and its effect on STAD tumor growth will contribute to further studies on the mechanisms of gastric adenocarcinoma development.

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GINS Complex Subunit 2 Facilitates Gastric Adenocarcinoma Proliferation and Indicates Poor Prognosis

Cited by 6 publications

References 32 publications

Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

The Molecular Pathogenesis of Tumor-Suppressive miR-486-5p and miR-486-3p Target Genes: GINS4 Facilitates Aggressiveness in Lung Adenocarcinoma

METTL3 regulates N6-methyladenosine modification of ANGPTL3 mRNA and potentiates malignant progression of stomach adenocarcinoma

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