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Published on: May 1, 2015
Integrase interactor 1 regulates proliferation, apoptosis and invasion in gastric cancer cells
Xiao-Chun Wang1, Yong Li, Li-Qiao Fan
1Department of General Surgery, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
Background:
Integrase interactor 1 (INI1), which encodes a component of the ATP-dependent chromatin remodeling hSWI-SNF complex, has been identified as a tumor suppressor in many tumors. Nonetheless, the role of INI1 in gastric tumor progression is not known exactly. The aim of this research was to investigate the effect of INI1 in the carcinogenesis and progression of gastric cancer.
Methods:
Gastric tumor tissues with different differentiation levels from clinical gastric carcinoma samples and adjacent control normal tissues were taken. Expression levels of INI1 were detected by quantitative reverse transcriptation-polymerase chain reaction (RT-PCR) and Western blotting. Gastric cancer cell line SGC7901 was transfected with INI1 eukaryotic expressing vector INI1-GFP. Cell proliferation activities were assessed by MTT; cell count and cell cycle were detected by flow cytometry (FCM); cell apoptosis were measured by TUNEL and FCM; cell migration and invasiveness were evaluated by wound healing and transwell assays. Expression levels of INI1 and proliferation-related genes including p16, p21, cyclin D1 and cyclin A, apoptosis genes p53, B-cell non-Hodgkin lymphoma-2 (Bcl-2), Bcl-2-associated x protein (Bax) and caspase-3, and invasion-related genes including intercellular adhesion molecule 1 (ICAM1), matrix metalloproteinase 2 (MMP2), MMP9 and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), were detected by quantitative RT-PCR and Western blotting.
Results:
INI1 expression levels were lower in gastric carcinoma compared with adjacent control normal tissues. Overexpression of INI1 in SGC7901 cells inhibited its proliferation and invasiveness, but increased anoikis and G(0)/G(1) cell number. INI1-GFP transfection upregulated expression of INI1 and proliferation related genes p16 and p21, apoptosis genes p53 and Bax, and invasion-related genes TIMP1; cyclin D1, cyclin A, Bcl2, ICAM1, MMP2 and MMP9 were downregulated, and there was no significant change in caspase 3 levels.
Conclusion:
INI1 plays a key role in gastric carcinogenesis by affecting proliferation, apoptosis and invasion.
Insights
Integrase interactor 1 (INI1) acts as a tumor suppressor in gastric cancer, inhibiting proliferation and invasion while promoting apoptosis. Lower INI1 expression correlates with gastric carcinoma, highlighting its crucial role in cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Integrase interactor 1 (INI1) is a component of the ATP-dependent chromatin remodeling hSWI-SNF complex.
- INI1 functions as a tumor suppressor in various cancers.
- The specific role of INI1 in gastric cancer progression remained unclear before this study.
Purpose of the Study:
- To investigate the effect of INI1 on gastric carcinogenesis.
- To elucidate the role of INI1 in the progression of gastric cancer.
Main Methods:
- Analyzed INI1 expression in gastric tumor tissues and adjacent normal tissues using RT-PCR and Western blotting.
- Overexpressed INI1 in gastric cancer cell line SGC7901 via INI1-GFP transfection.
- Assessed cell proliferation, cell cycle, apoptosis, migration, and invasion using MTT, FCM, TUNEL, wound healing, and transwell assays.
- Quantified expression of proliferation, apoptosis, and invasion-related genes.
Main Results:
- INI1 expression was significantly lower in gastric carcinoma tissues compared to normal tissues.
- INI1 overexpression in SGC7901 cells suppressed proliferation and invasiveness, increased anoikis, and promoted G(0)/G(1) phase arrest.
- INI1 upregulation led to increased expression of p16, p21, p53, Bax, and TIMP1, while decreasing cyclin D1, cyclin A, Bcl-2, ICAM1, MMP2, and MMP9.
Conclusions:
- INI1 plays a critical role in gastric carcinogenesis.
- INI1 influences gastric cancer progression by modulating cell proliferation, apoptosis, and invasion.
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