GINS2 was regulated by lncRNA XIST/miR-23a-3p to mediate proliferation and apoptosis in A375 cells.

Melanoma ranks second in aggressive tumors, and the occurrence of metastasis in melanoma results in a persistent drop in the survival rate of patients. Therefore, it is very necessary to find a novel therapeutic method for treating melanoma. It has been reported that lncRNA XIST could promote the tumorigenesis of melanoma. However, the mechanism by which lncRNA XIST regulates the progression of melanoma remains unclear. The proliferation of A375 cells was measured by clonal formation. Cell viability was detected by MTT assay. Flow cytometry was performed to detect cell apoptosis and cycle. The level of GINS2, miR-23a-3p, and lncRNA XIST was investigated by qRT-PCR. Protein level was detected by Western blot, and the correctness of prediction results was confirmed by Dual luciferase. In present study, GINS2 and lncRNA XIST were overexpressed in melanoma, while miR-23a-3p was downregulated. Silencing of GINS2 or overexpression of miR-23a-3p reversed cell growth and promoted apoptosis in A375 cells. Mechanically, miR-23a-3p directly targeted GINS2, and XIST regulated GINS2 level though mediated miR-23a-3p. Moreover, XIST exerted its function on cell proliferation, cell viability, and promoted the cell apoptosis of A375 cells though miR-23a-3p/GINS2 axis. LncRNA XIST significantly promoted the tumorigenesis of melanoma via sponging miR-23a-3p and indirectly targeting GINS2, which can be a potential new target for treating melanoma.

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

Gastric cancer is the one of the most lethal malignancies of digestive system. Identifying molecular biomarkers is invaluable in help predicting clinical outcomes and developing targeted chemotherapies. GINS complex subunit 2 (GINS2) plays an essential role in the initiation and elongation of DNA replication. Although there have been studies revealing the prognostic significance of GINS2 in breast cancer and lung cancer, its involvement and function in gastric cancer need to be elucidated. We retrospectively enrolled a cohort of gastric adenocarcinoma patients after surgical resection (n = 123). By analyzing the mRNA and protein levels of GINS2 in tissue samples, we found that GINS2 presented a higher expression in tumor tissues than in adjacent normal stomach tissues. Besides, GINS2 level was positively correlated with tumor size and gastric adenocarcinoma tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower GINS2 showed a better overall survival compared to those with higher GINS2 expression. In addition, cellular and xenograft experiments confirmed the role of GINS2 in facilitating tumor proliferation both in vitro and in vivo. To our knowledge, this is the initial finding on GINS2 in promoting gastric adenocarcinoma progression. In conclusion, our study revealed a pro-oncogenic role of GINS2 in gastric cancer.

LncRNA SNHG3 promotes bladder cancer proliferation and metastasis through miR-515-5p/GINS2 axis.

Growing evidence suggests that long non-coding RNAs (lncRNAs) are associated with carcinogenesis. LncRNA small nucleolar RNA host gene 3 (SNHG3) is up-regulated in various cancers and positively associated with poor prognosis of these cancers. However, the precise role of lncRNA SNHG3 in bladder cancer (Bca) remains unclear. In our research, we first reported that lncRNA SNHG3 was up-regulated in bladder cancer tissues and positively related to poor clinical prognosis. Moreover, knockdown of lncRNA SNHG3 significantly suppressed the proliferation, migration, invasion and EMT process of Bca cells in vitro and vivo. Mechanistically, we revealed that suppression of SNHG3 evidently enhanced miR-515-5p expression and decreased GINS2 expression at posttranscriptional levels. Moreover, SNHG3 positively regulated GINS2 expression by sponging miR-515-5p under a competing endogenous RNA (ceRNA) mechanism. To sum up, our study suggested lncRNA SNHG3 acted as a microRNA sponge and an oncogenic role in the progression of bladder cancer.

GINS2 facilitates epithelial-to-mesenchymal transition in non-small-cell lung cancer through modulating PI3K/Akt and MEK/ERK signaling.

Non-small-cell lung cancer (NSCLC) is a cancer with high morbidity and mortality. We aimed to define the effect of Go-Ichi-Ni-San complex subuint 2 (GINS2) acting on NSCLC. The expressions of GINS2 in NSCLC tissues and cells were detected using real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry (IHC). The relationship between GINS2 expression and NSCLC prognosis or clinicopathologic features was analyzed through statistical analysis. The overexpressed or downexpressed plasmids of GINS2 were transfected into NSCLC cell lines, and then cell proliferation, invasion, and migration viability were, respectively, determined by Cell Counting Kit-8 assay, transwell, and wound healing assay. The epithelial-mesenchymal transition (EMT) was observed and the EMT-related proteins were measured using IHC and western blot. The function of GINS2 in vivo was assessed by mice model. The related proteins of mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathways were evaluated using western blot. GINS2 expression was upregulated in NSCLC tissues and cell lines, and its high expression was correlated with the poor prognosis and several clinicopathologic features, such as TMN stages (tumor size, lymph node, and metastasis) and clinical stages. GINS2 enhanced NSCLC cell proliferation, migration, and invasion viability in vivo and in vitro. GINS2 also promoted NSCLC cells EMT. In addition, GINS2 could regulate phosphorylated proteins of PI3K p85, Akt, MEK, and ERK expressions, it revealed that GINS2 effected on PI3K/Akt and MEK/ERK pathways. GINS2 promoted cell proliferation, migration, invasion, and EMT via modulating PI3K/Akt and MEK/ERK signaling pathways. It might be a target in NSCLC treatment.

GINS2 promotes the progression of human HNSCC by altering RRM2 expression.

INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.

FABP4, GINS2 and CBX7 Expression in Cancer Cervix Tissues: Clinical, Pathological and Prognostic Implications.

Background & Objective: Cervical cancer spreads to the pelvic lymph nodes, leading to a high incidence of cancer recurrence and unfavorable survival rates. Therefore, there is an urgent need to detect new predictive biomarkers for the early assessment of pelvic lymph node status in patients with cervical cancer. The current study aimed to assess the expression of FABP4, GINS2, and CBX7 in cervical cancer tissue to detect their prognostic and predictive roles in developing lymph node metastases in patients with that cancer type. Methods: We collected the tissues from patients with cervical cancer and evaluated the expression of FABP4, GINS2, and CBX7 using immunohistochemistry. We evaluated the association between their expression and clinicopathological and prognostic parameters. Results: A high expression of FABP4 and GINS2 and a low expression of CBX7 were found to be positively associated with the old age group, large tumor size, high grade and lymphovascular involvement, para-uterine organ infiltration, advanced FIGO stage, chemotherapeutic resistance, and tumor recurrence. Conclusion: We demonstrated the oncogenic roles of FABP4 and GISN2 in addition to the on-co-suppressive roles of CBX7 in cervical cancer and their association with poor clinicopathological criteria and poor survival. Our results may indicate that FABP4, GISN2, and CBX7 could be considered predictive biomarkers of the occurrence of lymph node metastases in the cancer of the cervix preoperatively, which could be beneficial in the accurate preoperative design therapy.

Effect of GINS2 on proliferation and apoptosis in leukemic cell line.

Although previous researches have demonstrated that GINS2 express abundantly and abnormally in many malignant solid tumors, such as breast cancer, melanoma and hepatic carcinoma. However, the role and precise molecular mechanism in acute promyelocytic leukemia (APL) are rarely reported. In this current study, we investigated the possible effect and particular mechanism of GINS2 in occurrence and development of APL. We synthesized interference plasmid targeted GINS2 successfully in vitro and also constructed recombinant adenovirus vector carrying GINS2 gene in order to down-regulate or up-regulate GINS2 expression from two aspects of positive and negative in APL. After siRNA were transfected into HL60 cells, both GINS2 expression level of mRNA and protein in interfering group were down-regulated when compared with control groups. Together, MTT and flow cytometry technology showed that cell growth was significantly inhibited. Moreover, the expression lever of Bax was distinctly increased whereas Bcl2 was dramatically decreased in transfected group. Further experiments revealed that down-regulation of GINS2 expression inhibited DNA replication and had a G2/M phase block in HL60 cells. What's more, ATM, CHK2, and P53 gene could involve in the pathogenic signaling pathways of HL60 cells when GINS2 gene was down-regulated. On the contrary, after HL60 cells were infected by recombinant adenovirus vector which contained GINS2 gene, we observed that over-expression of GINS2 could promote HL-60 cell proliferation. What's more, GINS2 might implicate a potential target for leukemia gene therapy.

Identification of GINS2 prognostic potential and involvement in immune cell infiltration in hepatocellular carcinoma.

Background: GINS2 has been reported to have prognostic value in several solid tumors other than hepatocellular carcinoma (HCC), and its influence on tumor immunity has not been investigated thus far. Methods: The transcriptome profiles were retrieved from two public databases, GEO and TCGA. The median GINS2 expression was considered as cutoff to define GINS2 high and GINS2 low groups and to obtain differentially expressed genes. These genes were then subjected to KEGG pathway and gene ontology (GO) analysis and to gene set enrichment analysis (GSEA). Survival analyses according to GINS2 level were performed utilizing Kaplan-Meier plotter. TIMER database was adopted to investigate associations between GINS2 level and infiltrating immunocytes, and the correlation between immunocyte-related gene expression and GINS2 level was evaluated via GEPIA database. A 236-patient validation cohort were applied to confirm the bioinformatic results of TCGA and TIMER database. Results: GINS2 is augmented in tumorous tissues of HCC patients compared with nontumor specimens, and GINS2-overexpressed patients have poorer overall survival (OS) and disease-specific survival (DSS) than those with low GINS2 expression in HCC (P = 0.009 and P = 0.002 respectively). Cell cycle and DNA replication were two main processes that enriched in tumor cells overexpressed GINS2 gene (NES = 1.848, P = 0.007; and NES = 1.907, P = 0.005, respectively). Moreover, GINS2 correlates positively with markers of activated CD8+ and CD4+ T cells, as well as exhausted T lymphocytes. Conclusions: HCC patients overexpressed GINS2 have poorer prognoses than those with low GINS2 expression, possibly as a result of the function of GINS2 in cell cycle and DNA replication as well the exhaustion of T lymphocytes.

E2F1-mediated GINS2 transcriptional activation promotes tumor progression through PI3K/AKT/mTOR pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has high morbidity and mortality rates. It is therefore imperative to study the underlying mechanism of HCC to identify potential prognostic biomarkers and therapeutic targets. Recently, GINS2 has been identified to be a cancer-promoting gene in different cancer types. Nevertheless, the exact mechanism of GINS2 in HCC remains to be elucidated. To systematically explore the significance of GINS2, we first assessed the relative expression of GINS2 in pan-cancers based on data obtained from the HCCDB, TIMER, and TCGA databases. Then, we explored the clinical significance of GINS2 in HCC through Kaplan-Meier method as well as univariate and multivariate cox regression analysis. Additionally, functional enrichment analysis of GINS2 was done through GO, KEGG, PPI network, and immune cell infiltration analyses. Functional experiments were also conducted to investigate the biological significance of GINS2 in HCC cell lines. Our research revealed that GINS2 is involved in HCC progression and highlighted its potential value as a crucial diagnostic and therapeutic target for HCC.

GINS2 attenuates the development of lung cancer by inhibiting the STAT signaling pathway.

GINS complex subunit 2 (GINS2) controls DNA replication. GINS2 expression is upregulated in several kinds of aggressive tumors. However, the effect of GINS2 in lung cancer remains unclear. We performed TCGA database analysis to confirm the clinical significance of GINS2 in lung cancer. After silencing GINS2 in A549 cells, we performed MTT assays, flow cytometry assays, colony formation assays, cell cycle analyses and RNA sequence analysis to elucidate the effect of GINS2 on lung cancer. Moreover, we assessed tumor growth and analyzed body fluorescence in mice as a measure of tumor burden. The TCGA database analysis demonstrated that GINS2 mRNA and protein was highly expressed in three kinds of lung cancer tissues. Subsequently, knockdown of GINS2 inhibited cell proliferation, colony formation, cell cycle arrest and apoptosis in A549 cells. On the other hand, we also investigated the effect of GINS2 on tumor formation in vivo. The analysis of nude mouse tumors showed that the tumor volume and weight of shGINS2 mice were significantly smaller than those of the control mice. To reveal the mechanism of GINS2 in lung cancer, we collected A549 cells with GINS2 knockdown to examine the downstream gene expression changes. The results showed that STAT1 and STAT2 mRNA and protein expression were significantly upregulated after GINS2 knockdown in A549 cells. Our results suggest that GINS2 inhibits the proliferation of lung cancer cells by inhibiting the STAT signaling pathway, which may be a potential biomarker for the diagnosis or prognosis of lung cancer.

MicroRNA miR-502-5p inhibits ovarian cancer genesis by downregulation of GINS complex subunit 2.

Ovarian cancer (OC) is one of the most common malignancies with high incidence and mortality and the eighth most common cancer-associated mortality in women worldwide. Aberrant expression of the GINS complex subunit 2 (GINS2) gene and miR-502-5p has been associated with cancer progression. This study aims to investigate the specific molecular mechanism of the miR-502-5p-GINS2 axis in OC. GINS2 and miR-502-5p expression in OC tissues and cell lines was measured using RT-qPCR. Next, we investigated the interaction between miR-502-5p and GINS2 using a luciferase assay. The role of the miR-502-5p-GINS2 axis was detected by assessing cell proliferation, migration, and apoptosis levels, such as caspase-3 activity and caspase-3 protein expression, in the OC cell lines CaOV3 and SKOV3, respectively. MiR-502-5p expression was decreased, and GINS2 expression was dramatically elevated in OC tissues and cells. Upregulation of miR-502-5p expression repressed cellular proliferation and migration levels but increased the cellular apoptosis level. GINS2 overexpression enhanced the proliferation and migration levels but hampered OC cell apoptosis. Moreover, miR-502-5p inhibited GINS2 expression and suppressed OC tumorigenesis. miR-502-5p targeting GINS2 suppressed OC progression by inhibiting cell growth and promoting cell apoptosis. Hence, we provide a comprehensive understanding of OC involving both miR-502-5p and GINS2, which might be effective therapeutic targets for OC patients.

TRPM2-AS Promotes Bladder Cancer by Targeting miR-22-3p and Regulating GINS2 mRNA Expression.

BACKGROUND: Bladder cancer (BLCA) refers to the malignancy growth that spreads from the bladder linings to the bladder muscles. However, the impact of miR-22-3p and lncRNA TRPM2-AS on this tumor has generated divergent views in the literature. This research aimed to study the effects of lncRNA TRPM2-AS on BLCA and its interaction with miR-22-3p and GINS2 mRNA. METHODS: qRT-PCR was employed to measure the expression of TRPM2-AS, miR-22-3p and GINS2 mRNA in bladder tissues and cells. The subcellular localization of TRPM2-AS in T24 and 5637 cell lines was identified using a cell fractionation system. Luciferase assay, RIP assay and RNA pull-down assay were later performed to validate the direct binding relationship between TRPM2-AS, miR-22-3p and GINS2 mRNA. Several experiments were conducted to determine the viability, proliferation, colony formation and apoptosis of the cell lines. RESULTS: Findings indicated that TRPM2-AS was significantly upregulated in BLCA tissues and cell lines. Apart from that, it was observed that TRPM2-AS knockdown significantly inhibited the viability, proliferation and colony formation of BCLA cells, but it promoted the apoptosis of the BCLA cells. A significant downstream target of TRPM2-AS, miR-22-3p was found to show a lower expression level in BLCA tissues and cell lines. However, the inhibition of miR-22-3p considerably enhanced BLCA cell phenotypes. As well as discovering that GINS2 mRNA was a downstream target of miR-22-3p and was significantly upregulated in BLCA, experimental results also indicated that the knockdown of GINS2 suppressed BLCA cell phenotypes. CONCLUSION: This research confirmed that TRPM2-AS could promote BCLA by binding to miR-22-3p to increase GINS2 expression. This novel interactome in BLCA cell lines might provide more insights into BLCA therapy.

Mining the prognostic significance of the GINS2 gene in human breast cancer using bioinformatics analysis.

A number of studies have demonstrated the crucial functions of GINS2 within the GINS complex in various types of cancer. However, the molecular mechanisms and prognostic value of GINS2 in breast cancer remain unknown. The present study used; BC-GenExMiner, COSMIC, UCSC Xena, The Human Protein Atlas, GEPIA, cBioPortal, GeneMANIA, TIMER and Oncomine, in order to investigate gene expression, co-expression, clinical parameters and mutations in GINS2 in patients with breast cancer. Furthermore, the present study assessed the prognostic value of GINS2 in patients with breast cancer via the Kaplan-Meier plotter database. The results of the present study demonstrated that the mRNA levels of GINS2 were significantly higher in breast cancer tissue compared with normal tissue. In addition, high mRNA expression levels of GINS2 were associated with high Scarff-Bloom-Richardson status grades, a basal-like status and age (≤51 years); however, it was not associated with lymph node metastasis. The survival analysis revealed that increased GINS2 mRNA levels were associated with a worse prognosis for relapse-free survival in all patients with breast cancer, particularly in those with estrogen receptor-positive and progesterone receptor-positive subtypes. In addition, a positive association between the GINS2, CENPM and MCM4 genes was confirmed. The results of the present study suggest that GINS2 could be used as a potential prognostic biomarker for breast cancer. Nevertheless, further studies are necessary to confirm the effects of GINS2 on the pathogenesis and development of patients with breast cancer.

GINS2 Functions as a Key Gene in Lung Adenocarcinoma by WGCNA Co-Expression Network Analysis.

BACKGROUND: Lung adenocarcinoma is one of the malignant tumors in the world. This study aimed to explore the biological mechanism of GINS2 in lung adenocarcinoma. MATERIALS AND METHODS: Raw data were downloaded from GEO. WGCNA co-expression network and PPI network were established to identify the hub gene. The expression profile and clinical features of GINS2 were collected from TCGA-LUAD cohort. Survival analysis in TCGA-LUAD cohort was plotted by R package. GSEA was analyzed via GSEA software. MTS, Transwell and apoptosis assays were used to detect the proliferation, migration and apoptotic abilities of lung adenocarcinoma cells. RESULTS: GINS2 was identified as the hub gene via WGCNA co-expression network and PPI network. Higher GINS2 expressions were observed in TCGA-LUAD cohort, GSE32863 and clinical samples dataset. Overexpression of GINS2 had a significantly negative connection with poor survival outcome. GSEA results revealed that GINS2 could be enriched in "HALLMARK_G2M_CHECKPOINT", "HALLMARK_E2F_TARGETS", "HALLMARK_DNA_REPAIR" and "HALLMARK_MYC_TARGETS_V2". Overexpression of GINS2 promoted tumor cell proliferation and migration and suppressed cell apoptosis. CONCLUSION: Our results explored that GINS2 functioned as an oncogene in lung adenocarcinoma, and suggested that GINS2 could act as a promising prognosis biomarker for lung adenocarcinoma.

GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway.

Background and Objective: GINS complex subunit 2 (GINS2), a member of the GINS complex, is involved in DNA replication. GINS2 is upregulated in a variety of aggressive tumors, such as leukemia, breast cancer, and cervical cancer. However, the role of GINS2 in pancreatic cancer has still remained elusive. In this study, PANC-1 and BxPC-3 cell lines were chosen to perform experiments in vitro. Additionally, the effects of GINS2 interference on the cell viability, cell apoptosis, cell cycle, and tumor growth in nude mice were analyzed. Methods: We utilized pancreatic cancer cell lines that knocked down GINS2 expression using small interference RNA (siRNA) and evaluated GINS2 expression using Western blot analysis. To explore the function of GINS2 in pancreatic cancer cell lines in vitro, MTT assay and flow cytometry were used. Additionally, we investigated the potential mechanism of GINS2 interference by identifying the MAPK/ERK pathway using Western blotting. Finally, PANC-1 cells with GINS2 knockdown were subcutaneously injected into nude mice to evaluate the effects of GINS2 on tumor growth in vivo. Results: It was unveiled that GINS2 interference inhibited cell viability, induced cell cycle arrest at G1 phase, and enhanced apoptosis of pancreatic cancer cell lines. Western blot assay indicated that GINS2 interference increased the expression level of Bax, while the expression level of Bcl-2 was remarkably decreased. In addition, the expression levels of CDK4, CDK6, and Cyclin D1 were significantly reduced after treatment with GINS2 siRNA. Furthermore, GINS2 interference drastically attenuated the expression levels of MEK, p-MEK, ERK, and p-ERK, belonging to the MAPK/ERK pathway. The results of an established cancer xenograft model revealed that nude mice transplanted with cells expressing negative control (NC) exhibited larger and heavier tumors, while volume and weight of tumor were remarkably reduced in ones transplanted with cells expressing GINS2 siRNA. Conclusions: GINS2 interference inhibited cell viability, induced cell cycle arrest, and promoted cell apoptosis of pancreatic cancer cell lines via the MAPK/ERK pathway, and our findings may be valuable for treating pancreatic cancer.

Knockdown of GINS2 inhibits proliferation and promotes apoptosis through the p53/GADD45A pathway in non-small-cell lung cancer.

Lung cancer is a malignant tumour type with the highest morbidity and mortality, and non-small-cell lung cancer (NSCLC) is the most common pathological type. GINS complex subunit 2 (GINS2) is a member of the GINS family and is closely related to DNA replication and damage, participates in cell cycle regulation and plays a key role in cell proliferation and apoptosis. In the present study, we aimed to explore the role and underlying molecular mechanism of GINS2 in the development of NSCLC. The results showed that GINS2 is significantly increased in NSCLC tissues and cell lines. Knockdown of GINS2 significantly decreases cell proliferation, causing G2/M phase cell cycle arrest. Knockdown of GINS2 reverses the effect of nocodazole on the levels of cyclin-dependent kinase 1 (CDK1) and cyclin-B1. Meanwhile, knockdown of GINS2 significantly elevates the apoptosis rate and apoptosis-related protein Bax and decreases Bcl-2. In addition, GINS2 knockdown induces an increase in the levels of p53 and growth arrest and DNA damage 45A (GADD45A). Co-transfection with GINS2-siRNA and siRNA against p53 (p53-siRNA) or co-transfection with GINS2-siRNA and siRNA against GADD45A (GADD45A-siRNA) partially reverses the effects of GINS2 knockdown on cell proliferation and apoptosis. Taken together, these results indicate that GINS2 knockdown down-regulates cell proliferation, induces G2/M phase cell cycle arrest and increases apoptosis, possibly through the p53/GADD45A pathway.

Tissue-Specific Requirement for the GINS Complex During Zebrafish Development.

Efficient and accurate DNA replication is particularly critical in stem and progenitor cells for successful proliferation and survival. The replisome, an amalgam of protein complexes, is responsible for binding potential origins of replication, unwinding the double helix, and then synthesizing complimentary strands of DNA. According to current models, the initial steps of DNA unwinding and opening are facilitated by the CMG complex, which is composed of a GINS heterotetramer that connects Cdc45 with the mini-chromosome maintenance (Mcm) helicase. In this work, we provide evidence that in the absence of GINS function DNA replication is cell autonomously impaired, and we also show that gins1 and gins2 mutants exhibit elevated levels of apoptosis restricted to actively proliferating regions of the central nervous system (CNS). Intriguingly, our results also suggest that the rapid cell cycles during early embryonic development in zebrafish may not require the function of the canonical GINS complex as neither zygotic Gins1 nor Gins2 isoforms seem to be present during these stages.

GINS complex subunit 2 (GINS2) plays a protective role in alcohol-induced brain injury.

Acute alcohol intoxication is a central nervous system disease that accounts for a large number of hospital admissions. In the present study, we have explored the role of GINS complex subunit 2 (GINS2) in acute alcohol intoxication and alcohol-induced brain injury. We began by determining that GINS2 mRNA expression was significantly increased in the serum of patients with alcohol abuse. We then found that GINS2 is increased in mouse brains after alcohol consumption. To explore the role of GINS2 in alcohol-induced microglia function, we knocked down GINS2 in mouse microglia and then treated the cells with alcohol. Knockdown of GINS2 significantly increased alcohol-induced ROS production and the oxidative stress marker malondialdehyde. To explore if GINS2 is involved in alcohol-induced microglia apoptosis, we examined cell viability in GINS2 knockdown cells by TUNEL staining and caspase activity assays. Consistently, results showed that alcohol-induced cell apoptosis was promoted by knockdown of GINS2. Finally, we assessed expression levels of inflammatory factors in GINS2 knockdown microglial cells as well as the effects of GINS2 knockdown on NF-κB signalling. Inflammatory factors were stimulated by alcohol and further promoted by GINS2 knockdown, and GINS2 knockdown promoted alcohol-induced NF-κB activity in microglia.

Loss of GINS2 inhibits cell proliferation and tumorigenesis in human gliomas.

AIMS: In this study, we examined the expression of GINS2 in glioma and determined its role in glioma development. METHODS: The protein expression of GINS2 was assessed in 120 human glioma samples via immunohistochemistry. Then, we suppressed the expression of GINS2 in glioma cell strains U87 and U251 using a short hairpin RNA lentiviral vector. In addition, RNA sequencing and bioinformatics analysis were performed on glioma cells before and after GINS2 knockdown. Subsequent co-immunoprecipitation and western blot experiments indicated possible downstream regulatory molecules. RESULTS: The present results showed that GINS2 can accelerate the growth of glioma cells, whereas the suppression of GINS2 expression decreased the proliferation and tumorigenicity of glioma cells. Mechanism research experiments proved that GINS2 can block the cell cycle by regulating certain downstream molecules, such as MCM2, ATM, and CHEK2. CONCLUSION: GINS2 is closely related to the occurrence and development of glioma, and is likely to become a prognostic marker for glioma patients, as well as a potential therapeutic target in the treatment of glioma.

GINS2 regulates matrix metallopeptidase 9 expression and cancer stem cell property in human triple negative Breast cancer.

GINS2, a subunit of GINS complex, is critical for the initiation of DNA replication and DNA replication fork progression. The expression of GINS2 is misregulated in many malignant tumors, such as leukemia, breast cancer and melanoma. However, the role of GINS in breast cancer remains poorly characterized. We investigate the possible effect and particular mechanism of GINS in breast cancer cells. We showed that expression of GINS2 is enriched in triple negative breast cancer (TNBC) cell lines. Furthermore, GINS2 knockdown decreased the growth, invasive ability and stem-like property of TNBC cells. Mechanistically, silencing of GINS2 in TNBC cells caused dramatic decrease of matrix metalloproteinase-9 (MMP9). Finally, the abundance of GINS2 correlated with the advance stages of tumor in human TNBC patients. Our studies provided insight into the molecular regulation of TNBC progression and invasion. More importantly, our data suggest that GINS2 could be an outstanding therapeutic target for inhibiting invasive TNBC growth and metastasis.