Wenbo Du1, Ding Li2, Xiaomin Guo3, Ping Li4, Xin Li5, Shuping Tong6, Junhui Tong7, Lihua Kuang8, Daoming Liang9. 1. Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China. 2. Department of General Surgery, Nantong Tumor Hospital, Nantong, Jiangsu, China. 3. School of Mongol Medicine, Chuxiong Medical College, Chuxiong, Yunnan, China. 4. Academic Office, Hainan Medical University, Haikou, Hainan, China. 5. School of Mongol Medicine, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China. 6. Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia, China. 7. Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China. 8. Department of Internal Medicine, Shenzhen Pingle Orthopaedic Hospital, Pingshan New District, Shenzhen, China. 9. Department of Gastrointestinal Surgery, Kunming Medical University Second Hospital, Kunming, Yunnan, China.
Abstract
Background: Gastric cancer (GC) is a global leading source of cancer-associated deaths. Circular RNAs (circRNAs) are a new type of non-coding RNA and promising biomarkers for diagnosis of multiple diseases such as cancer. Methods: Circ-PRMT5 expression was validated in 90 GC patient tissues and 6 different GC cells by qRT-PCR. Sublocalization of circ-PRMT5 in GC cells was determined in isolated nuclear and cytoplasmic RNAs. CircInteractome and miRanda were used to predict binding sites between circ-PRMT5 with micRNAs, and micRNAs with target mRNA. The correlation between genes was determined by the Pearson correlation analysis. The molecular mechanism was demonstrated by RNA in vivo precipitation, point mutation, luciferase activity and rescue experiments. Results: Circ-PRMT5 expression was significantly higher in GC than in adjacent normal tissues, and GC patients with circ-PRMT5 high expression had shorter survival times. Functionally, circ-PRMT5 silence inhibited GC cell growth and invasion. Mechanism analysis showed that circ-PRMT5 sponged miR-145/miR-1304 to upregulate MYC expression and GC development. Conclusion: Our findings demonstrated that circ-PRMT5 function as an oncogene in GC patients by targeting miR-145/miR-1304/MYC axis. High circ-PRMT5 expression may provide a poor prognostic indicator of survival in GC patients and targeting circ-PRMT5/miR-145/miR-1304/MYC axis may be a novel therapeutic strategy for GC.
Background: Gastric cancer (GC) is a global leading source of cancer-associated deaths. Circular RNAs (circRNAs) are a new type of non-coding RNA and promising biomarkers for diagnosis of multiple diseases such as cancer. Methods: Circ-PRMT5 expression was validated in 90 GCpatient tissues and 6 different GC cells by qRT-PCR. Sublocalization of circ-PRMT5 in GC cells was determined in isolated nuclear and cytoplasmic RNAs. CircInteractome and miRanda were used to predict binding sites between circ-PRMT5 with micRNAs, and micRNAs with target mRNA. The correlation between genes was determined by the Pearson correlation analysis. The molecular mechanism was demonstrated by RNA in vivo precipitation, point mutation, luciferase activity and rescue experiments. Results: Circ-PRMT5 expression was significantly higher in GC than in adjacent normal tissues, and GCpatients with circ-PRMT5 high expression had shorter survival times. Functionally, circ-PRMT5 silence inhibited GC cell growth and invasion. Mechanism analysis showed that circ-PRMT5 sponged miR-145/miR-1304 to upregulate MYC expression and GC development. Conclusion: Our findings demonstrated that circ-PRMT5 function as an oncogene in GCpatients by targeting miR-145/miR-1304/MYC axis. High circ-PRMT5 expression may provide a poor prognostic indicator of survival in GCpatients and targeting circ-PRMT5/miR-145/miR-1304/MYC axis may be a novel therapeutic strategy for GC.