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SMU1 Knockdown Suppresses Gastric Carcinoma Growth, Migration, and Invasion and Modulates the Cell Cycle
Meirui Qian1, Xue Liang1, Qingmei Zeng1,2
1Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.
Introduction:
The role of SMU1 in DNA replication and RNA splicing is well-established, yet its specific function and dysregulated mechanisms in gastric cancer (GC) remain inadequately elucidated. This study seeks to investigate the potential oncogenic and progression-promoting effects of SMU1 in GC, with the ultimate goal of informing novel approaches for treatment and diagnosis.
Methods:
The study investigated the expression levels of SMU1 in GC and adjacent normal tissues by analyzing data from the TCGA (27 tissue pairs) and GEO (47 tissue pairs) databases. Immunohistochemistry was used to examine 277 tumor tissue and adjacent non-tumor tissue spots from GC tissue chips, along with relevant follow-up information. The study further assessed the proliferation, invasion, and migration capabilities of cells by manipulating SMU1 expression levels and conducting various assays, including CCK-8, EdU incorporation, colony formation, transwells, flow cytometry, and subcutaneous tumorigenesis assays.
Results:
Our study revealed a significant upregulation of SMU1 mRNA and protein levels in GC tissues compared to adjacent tissues. Univariate and multivariate Cox analysis demonstrated that elevated levels of SMU1 were independent prognostic factors for GC prognosis (P = 0.036). Additionally, median survival analysis indicated a significant association between high SMU1 expression and poor prognosis in GC patients (P = 0.0002). In experiments conducted both in vivo and in vitro, it was determined that elevated levels of SMU1 can enhance the proliferation, invasion, and migration of GC cells, whereas suppression of SMU1 can impede the progression of GC by modulating the G1/S checkpoint of the cell cycle.
Conclusions:
Our research introduces the novel idea that SMU1 could serve as a prognostic marker for GC progression, influencing cell proliferation through cell cycle activation. These results offer valuable insights into the understanding, diagnosis, and management of gastric carcinoma.
Insights
SMU1 is upregulated in gastric cancer (GC) and promotes tumor progression by enhancing cell proliferation and migration. SMU1 may serve as a prognostic marker for GC, offering new diagnostic and treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The role of SMU1 in DNA replication and RNA splicing is known, but its specific function in gastric cancer (GC) is unclear.
- Investigating SMU1's oncogenic role in GC is crucial for developing new treatment and diagnostic approaches.
Purpose of the Study:
- To elucidate the function and dysregulated mechanisms of SMU1 in gastric cancer.
- To assess the potential of SMU1 as an oncogenic driver and prognostic marker in GC.
Main Methods:
- Analyzed SMU1 expression in GC vs. normal tissues using TCGA and GEO databases.
- Performed immunohistochemistry on 277 GC tissue samples.
- Conducted in vitro and in vivo assays to evaluate the impact of SMU1 on GC cell proliferation, invasion, and migration.
Main Results:
- SMU1 mRNA and protein levels were significantly upregulated in GC tissues.
- High SMU1 expression correlated with poor GC prognosis and was an independent prognostic factor.
- Elevated SMU1 enhanced GC cell proliferation, invasion, and migration; SMU1 suppression impeded GC progression by modulating the G1/S cell cycle checkpoint.
Conclusions:
- SMU1 acts as a prognostic marker for GC progression by influencing cell proliferation via cell cycle activation.
- Findings provide insights into GC understanding, diagnosis, and management.
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