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RAI14 silencing suppresses progression of esophageal cancer via the STAT3 pathway
Jianlin Wang1,2,3, Yun Cai4, Judong Luo3
1Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University and Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, China.
Abstract:
Esophageal cancer (EC) is an aggressive malignancy that has an unclear molecular pathogenesis. Although retinoic acid induced 14 (RAI14) is involved in various cancer processes, the relationship between EC and RAI14 has not been elucidated. Our study reported the oncogenic function of RAI14 and its underlying mechanisms in EC. The Cancer Genome Atlas (TCGA) database revealed that RAI14 was upregulated in EC, and this upregulation correlated with T stage, histologic grade, and poor clinical prognosis. RAI14 was evaluated in EC cell lines, and the overexpression of RAI14 promoted cell proliferation, migration, and invasion in vitro. Conversely, RAI14 knockdown induced apoptosis and cell cycle arrest. RAI14 activated STAT3, upregulated Mcl-1 and cyclin D1, and inhibited cleaved caspase-3. Inhibition of STAT3 restored the oncogenic effect of RAI14, and RAI14 silencing restrained tumor growth and the protein level of Ki67 in vivo. Our results suggest that RAI14 regulates the STAT3 pathway and acts as an oncogene during EC progression.
Insights
Retinoic acid induced 14 (RAI14) acts as an oncogene in esophageal cancer (EC). Upregulation of RAI14 promotes EC cell growth and invasion by activating the STAT3 pathway, indicating its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Esophageal cancer (EC) is an aggressive malignancy with poorly understood molecular mechanisms.
- The role of retinoic acid induced 14 (RAI14) in EC progression remains unclear.
Purpose of the Study:
- To investigate the function and molecular mechanisms of RAI14 in esophageal cancer.
- To determine the correlation between RAI14 expression and clinical outcomes in EC patients.
Main Methods:
- Analysis of TCGA database for RAI14 expression in EC.
- In vitro studies using EC cell lines to assess the effects of RAI14 overexpression and knockdown on cell behavior (proliferation, migration, invasion, apoptosis, cell cycle).
- In vivo studies involving tumor xenografts to evaluate the impact of RAI14 silencing on tumor growth.
Main Results:
- RAI14 was found to be upregulated in EC, correlating with advanced T stage, higher histologic grade, and poorer prognosis.
- RAI14 overexpression enhanced EC cell proliferation, migration, and invasion, while knockdown induced apoptosis and cell cycle arrest.
- RAI14 activated the STAT3 pathway, leading to increased Mcl-1 and cyclin D1 levels and decreased cleaved caspase-3.
- STAT3 inhibition reversed the oncogenic effects of RAI14, and RAI14 silencing suppressed tumor growth and Ki67 expression in vivo.
Conclusions:
- RAI14 functions as an oncogene in esophageal cancer progression.
- RAI14 promotes EC tumorigenesis by regulating the STAT3 signaling pathway.
- RAI14 represents a potential therapeutic target for esophageal cancer treatment.
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