Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effect of GINS2 on proliferation and apoptosis in leukemic cell line. 2427 54

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.
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PMID:GINS2 regulates matrix metallopeptidase 9 expression and cancer stem cell property in human triple negative Breast cancer. 2782 49

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.
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PMID:GINS2 affects cell viability, cell apoptosis, and cell cycle progression of pancreatic cancer cells via MAPK/ERK pathway. 3262 12