1. Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
2. Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Pettenkoferstrasse 8a, 80336 Munich, Germany.
3. Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
4. Department of General Surgery, Nanjing First Hospital, The Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
5. Institute and Clinic for Occupational, Social and Environmental Medicine, LMU University Hospital Munich
6. Jiangsu Province Hospital, The first affiliated hospital of Nanjing Medical University, Nanjing, Jiangsu, China
7. Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai, China.
8. Department of Orthopedic Oncology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
*These authors contributed equally to this work.
Circular RNAs (circRNAs) is a novel class of non-coding RNAs resulting from the non-canonical splicing of linear pre-mRNAs. However, the role of circRNAs in gastric cancer (GC) remains indistinct. This study aims to explore their potential modulation in GC and its prognostic value. We first screen for circRNA expression patterns in GC through GC and adjacent noncancerous tissues by microarray. Based on the bioinformatics analysis of the microarray data, we screened out a novel circRNA, circ-PTPDC1. Then we demonstrated that circ-PTPDC1 was up-regulated in GC cells, tissues, and serum. Its overexpression was positively correlated with age, invasion depth, advanced clinical stages, and worse survival in patients with GC. We further revealed that circ-PTPDC1 promotes the proliferation, migration, and invasion of GC cell lines via sponging miR-139-3p by regulating ELK1. Importantly, we identified that circ-PTPDC1 promotes tumor upgrowth and metabasis in vivo. Additionally, we established its prognostic prediction model based on the follow-up data of the patients. Our study revealed a novel regulatory mechanism and a comprehensive landscape of circ-PTPDC1 in GC, suggesting that circ-PTPDC1 has the potential to be a biomarker for early detection and prognostic prediction of GC.
Keywords: gastric cancer, circ-PTPDC1, miR-139-3p, ELK, prognosis