CircRNA_100876 Is Upregulated in Gastric Cancer (GC) and Promotes the GC Cells' Growth, Migration and Invasion via miR-665/YAP1 Signaling.

Xiaosheng Lin,Huaiming Wang,Cong Huang,Zhian Chen,Yongming Zeng

doi:10.3389/fgene.2020.546275

Abstract

The present study aimed to investigate the biological function and relative mechanisms of circRNA_100876 in gastric cancer (GC). To this end, quantitative real-time polymerase chain reaction (RT-qPCR) was performed to examine the expression of circRNA_100876 and miR-665 in GC tissues and cells, and circRNA_100876 expression was depleted by the transfection of circ_100876-targeting siRNAs. CCK-8, flow cytometry, and Transwell assays were applied to examine GC cell cycle distribution, proliferation, apoptosis, migration, and invasion abilities. Proteins related to apoptosis and epithelial-mesenchymal transition (EMT) were detected by western blotting. Luciferase reporter assays were conducted to verify the direct target site between circRNA_100876 and miR-665. Our study confirmed that circRNA_100876 was highly expressed in GC lesions compared with the adjacent normal tissues (P < 0.001). High circRNA_100876 expression was negatively associated with survival outcome (P = 0.000). Furthermore, the down-regulation of circRNA_100876 could inhibit GC cell proliferation, invasion, and migration by suppressing the EMT pathway. Further study suggested that circRNA_100876 could act as a competing endogenous RNA by sequestering miR-665, and luciferase activity assay indicated that circRNA_100876 could bind directly with miR-665. Moreover, we found that Yes-associated protein 1 (YAP1) was the downstream target gene of miR-665, miR-665 knockdown could up-regulate YAP1 expression in MKN45 cells, and YAP1 knockdown could inhibit MKN45 cell proliferation, migration and invasion. Therefore, we demonstrated that circRNA_100876 over-expression in GC could promote GC tumor growth, migration and invasion and exert its effects through miR-665/YAP1 signaling.

Highlights

Gastric cancer (GC) is one of the most prevalent malignancy worldwide and is well known for its high morbidity and mortality
We found that compared with the adjacent normal tissues, circRNA_100876 expression was significantly upregulated in GC tissues (P < 0.001, Figure 1B)
CircRNA_100876 expression was more likely to be highly expressed in patients with tumor size >5 cm compared to those with tumor size

Summary

Introduction

Gastric cancer (GC) is one of the most prevalent malignancy worldwide and is well known for its high morbidity and mortality. CircRNA_100876 Promotes Tumorigenesis in GC rate remains unsatisfactory (Shuyama et al, 2007; Lin et al, 2017). This is largely due to the highly limited understanding of the exact molecular mechanism responsible for the early occurrence and development of GC. It is urgent and important to screen effective molecular markers, achieve early diagnosis and survival prediction for groups at high risk of GC, and further study the mechanism of GC occurrence and development (Khalil et al, 2009; Shih et al, 2017). Accumulating research has elucidated that circRNAs are widely involved in diverse physiological and pathological processes, especially tumor generation and development (Hansen et al, 2013b)

Results

Discussion

Conclusion