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Circular RNA hsa_circ_0009172 suppresses gastric cancer by regulation of microRNA-485-3p-mediated NTRK3

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Abstract

Gastric cancer is the third leading cause of cancer-related death worldwide, with relapse and metastasis being major contributors to the mortality. Circular RNAs (circRNAs) have been at the center of several researches and some circRNAs have been indicated to be involved in gastric cancer as sponges. Nevertheless, the mechanism underlying the function of circRNA remains largely unclear. Therefore, this study was conducted with the main objective of screening the associated circRNA in gastric cancer and exploring its mechanism. Expression of hsa_circRNA_0009172 was validated in gastric cancer tissues and cell lines after the correlation between hsa_circRNA_0009172 and prognosis was determined. Moreover, the binding site between miR-485-3p and hsa_circRNA_0009172 or NTRK3 was verified using dual luciferase assay and RNA pull down. Function-gain and -loss experiments were performed for the purpose of detecting the effect of hsa_circRNA_0009172 in vivo and in vitro as well as its mechanism with microRNA (miRNA)-485-3p and NTRK3 in gastric cancer. The hsa_circRNA_0009172 expression was downregulated in gastric cancer tissues and cell lines, indicating a positive association with patient prognosis. Functionally, hsa_circ_0009172 overexpression inhibited proliferative, invasive and migrative potential of gastric cancer cells as well as epithelial-mesenchymal transition (EMT)-related proteins by sponging miR-485-3p to inhibit NTRK3, while miR-485-3p overexpression could reverse the inhibitory effect of hsa_circ_0009172 on gastric cancer. Furthermore, either up-regulation of hsa_circ_0009172 or down-regulation of miR-485-3p led to the suppression of xenograft tumor growth in nude mice. In conclusion, hsa_circ_0009172 serves as a tumor suppressor in gastric cancer by targeting miR-485-3p/NTRK3 axis.

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Fig. 1: hsa_circRNA_0009172/miR-485-3p/NTRK3 axis is associated with development of gastric cancer.
Fig. 2: hsa_circRNA_0009172 expression is related with poor prognosis of gastric cancer patients.
Fig. 3: Low hsa_circRNA_0009172 expression promotes malignant phenotypes of gastric cancer cells.
Fig. 4: hsa_circRNA_0009172 binds to miR-485-3p.
Fig. 5: miR-485-3p eliminates the suppression of hsa_circRNA_002178 to gastric cancer progression.
Fig. 6: hsa_circRNA_0009172 regulates NTRK3 expression through sponging miR-485-3p.
Fig. 7: hsa_circRNA_0009172 and miR-485-3p participates in tumor growth.

Data availability

The datasets generated/analyzed during the current study are available.

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Acknowledgements

We would like to give our sincere appreciation to the reviewers for their helpful comments on this article.

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Hao Wang, Nan Wang, Xiaoli Zheng, Lei Wu, Chengcheng Fan, Xue Li, Ke Ye, and Suxia Han designed the study. Hao Wang, Nan Wang, and Xiaoli Zheng collated the data, carried out data analyses, and produced the initial draft of the manuscript. Lei Wu, Chengcheng Fan, Xue Li, Ke Ye, and Suxia Han contributed to drafting the manuscript. All authors have read and approved the final submitted manuscript.

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Correspondence to Suxia Han.

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Wang, H., Wang, N., Zheng, X. et al. Circular RNA hsa_circ_0009172 suppresses gastric cancer by regulation of microRNA-485-3p-mediated NTRK3. Cancer Gene Ther (2021). https://doi.org/10.1038/s41417-020-00280-7

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