Circular RNA hsa_circ_0000751 serves as a microRNA-488 sponge to suppress gastric cancer progression via ubiquinol-cytochrome c reductase core protein 2 regulation

ABSTRACT

Circular RNAs (circRNAs) are RNA molecules that do not encode proteins but are known to regulate tumor progression. This study was designed to explore the underlying mechanism driving circRNA-mediated modulation of gastric cancer (GC). Bioinformatics analysis of gene chip GSE83521 was used to identify multiple circRNAs that were differentially regulated in matched GC and adjacent normal tissues. The circRNA with the largest variation in expression (hsa_circ_0000751) was selected for further examination. The expression profile of hsa_circ_0000751 and its target-specific interactions with microRNAs (miRNAs) and downstream gene transcripts were determined using quantitative real-time polymerase chain reaction, luciferase reporter assays, and rescue assays in human tissues and cells. The relationship between hsa_circ_0000751 expression and the clinicopathological parameters of 25 GC patients was analyzed. Furthermore, ubiquinol-cytochrome c reductase core protein 2 (UQCRC2), a GC suppressor, was detected via western blot analysis. The results showed that hsa_circ_0000751 levels were markedly downregulated in GC tissues and cell lines, which were also inversely proportional to the stage of tumor-node-metastasis (TNM) classification, tumor volume, and lymph node metastasis in GC patients. Conversely, hsa_circ_0000751 overexpression suppressed tumor progression, migration, and invasion in vitro and in vivo. From our results, we showed that hsa_circ_0000751 may serve as a miRNA sponge to suppress the activity of miR-488, thereby increasing the expression of the miR-488-target gene, UQCRC2, and limiting GC progression. Given its negative regulation of oncogenic miRNAs, the hsa_circ_0000751/miR-488/UQCRC2 axis may be crucial in the development of novel GC therapies.

KEYWORDS:

• Circular RNA
• hsa_circ_0000751
• miR-488
• UQCRC2
• gastric cancer

Disclosure statement

The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

Data Availability Statement

All data generated or analyzed during this study are included in this published article.

Ethics approval and consent to participate

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by The Medical Ethics Committee of Wuhan University (approval number: 2,015,011), and written informed consent was obtained from all patients.

Author Contributions

DWW, FS and MHF designed study. DWW and FS performed the experiments. DWW, FS and MHF provided the clinical specimens, analyzed the data and wrote the manuscript. All the authors read and approved the final manuscript.

Additional information

Funding

This project was supported in part by grants from National Natural Science Foundation of China (No. 81072152 and No. 81770283), Natural Science Foundation of Hubei Province (No. 2015CFA027), Research Foundation of Health and Family Planning Commission of Hubei Province (N0. WJ2015MA010 and No. WJ2017M249), Clinical Medical Research Center of Peritoneal Cancer of Wuhan (No.2015060911020462), Subsidy Project of No.1 Hospital of Lanzhou University (ldyyyn2018-13) and Innovation fund of universities in Gansu Province (2020B-009), Natural Science Foundation of Gansu Province youth Fund(21JR7RA386)