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Published on: January 21, 2012
The Dual Role of RBBP7 in Esophageal Squamous Cell Carcinoma: Cell Context-Dependent Impacts on Proliferation and
Yafen Li1,2, Shuai Lu3, Hui Yao1
1Department of Clinical Pharmacy, Wanbei Coal and Electricity Group General Hospital, Suzhou, Anhui, People's Republic of China.
Background:
Radiotherapy resistance contributes to poor prognosis in esophageal squamous cell carcinoma (ESCC). Retinoblastoma-binding protein 7 (RBBP7) is a nuclear protein, and it can promote or inhibit tumor progression in cancer, but its function in ESCC cells and impact on radiosensitivity remains unclear.
Methods:
RBBP7 expression in cancer was analyzed using an online website. The expression levels of RBBP7 in ESCC cells (TE-1 and KYSE-150) and tissues were tested. Cells were subjected to RBBP7 gene silencing and irradiation (IR). Assays included CCK-8, clonogenic survival, flow cytometry (apoptosis/cell cycle), ROS detection, and Western blotting for DNA damage (γ-H2AX) and STAT3 signaling. Additionally, pathological tissue specimens and clinical data from ESCC patients were used to explore the expression of RBBP7.and its relationship with the clinical parameters of patients.
Results:
RBBP7 was overexpressed in malignant tumors. In ESCC cells, the mRNA and protein of RBBP7 were also highly expressed. After silencing RBBP7 combined with IR treatment, contradictory effects were observed between cell lines: In well-differentiated TE-1 cells, RBBP7 knockdown suppressed proliferation, enhanced radiosensitivity (SER=1.370), increased ROS/DNA damage (γ-H2AX), promoted apoptosis, and reduced STAT3 activation (possibly through STAT3 signaling). In poorly-differentiated KYSE-150 cells, knockdown promoted proliferation, decreased radiosensitivity (SER=0.775), reduced apoptosis, and increased p-STAT3. In addition, knockdown caused S-phase arrest (TE-1) versus G0/G1 arrest (KYSE-150), with divergent CDK4/Cyclin D1 regulation. Clinical analysis confirmed RBBP7 positivity correlated with tumor differentiation, TNM stage, and radiotherapy method.
Conclusion:
RBBP7 is highly expressed in ESCC, and it exerts cell context-dependent dual roles in ESCC, leading to differences in cellular radiosensitivity, possibly mediated through STAT3 signaling. This dichotomy highlights its potential as a differentiation status-specific therapeutic target.
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