Long Non-Coding RNA LINC01224 Promotes GC Progression via miR-193a-5p/YES1 Axis

Background:  Gastric cancer (GC) is one of the most common malignant tumors of the digestive tract with a high degree of malignancy and poor clinical prognosis. There is considerable evidence that long non-coding RNA (lncRNA) is associated with the progression of GC. However, as a lncRNA, the relationship between LINC01224 and GC remains unclear. Methods:  The expression and correlation of LINC01224, miR-193a-5p and YES1 in GC were analyzed by using the database information of TCGA and GTEx. We collected tumor tissues and paired paracancerous tissue specimens from 76 GC patients to detect the expression levels of LINC01224, miR-193a-5p and YES1, and further analyzed the correlation between LINC01224 and clinicopathological features. The effect of LINC01224 on GC cell phenotype was detected by CCK-8, EdU, flow cytometry and clone formation. A subcutaneous tumor model was established to analyze the growth of GC cells after LINC01224 gene knockout. The interaction among LINC01224, miR-193a-5p and YES1 were determined by RNA pull-down, RNA immunoprecipitation and luciferase reporter assay. Results:  We found that a novel oncogene LINC01224 was highly expressed in GC, which was positively correlated with TNM staging and shortened overall survival time. LINC01224 gene knockdown inhibits GC cell proliferation, induces apoptosis and G1 phase arrest. Mechanistically, LINC01224 promotes the expression of YES1 in GC cells by competitively binding to miR-193a-5p. Interestingly, miR-193a-5p inhibitors and up-regulation of YES1 reversed the effects of knock-down LINC01224 on the proliferation, apoptosis and cell cycle of GC cells, whereas transfected mutant LINC01224 plasmids did not. Conclusion:  Our findings confirm that LINC01224 is a potential prognostic marker of GC. LINC01224/miR-193a-5p/YES1 axis plays a vital role in the proliferation, cell cycle and apoptosis of GC cells, which provides a potentially important diagnostic and therapeutic target for GC. Funding Statement: This study was supported by scientific and technological project of Xi'an[2017113SF/YX007(11)], Shaanxi Provincal project of scientific and technological innovation team (2017KCT-28) and Shaanxi Natural Science Foundation (2020JQ-947), NSFC (8142012), Shaanxi Natural Science Foundation (2015JQ8321), Shaanxi Natural Science Foundation (2019JM-547), Operating Expenses of Basic Scientific Research Project of Xi'an Jiaotong University (xzy012019112), scientific and technological project of Xi'an (2019114613YX001SF03). Declaration of Interests: The authors declare that they have no conflicts of interests. Ethics Approval Statement: The study was conducted with the approval of the ethics committee of Shaanxi provincial people's hospital. All patients in the study signed written informed consent before enrollment. All animal experiments were conducted under the international commission's guidelines for the care and use of laboratory animals with a protocol approved by the Ethics Committee of Shaanxi Provincial People's Hospital.