Effect of the Up-Regulation of Circular RNA Hsa_circ_0069767 Derived from C-KIT on the Biological Behavior of Multiple Myeloma Cells

Fang Chen; Xiaohui Wang; Shuang Fu; Shaokun Wang; Yu Fu; Zhuogang Liu; Jihong Zhang

doi:10.2147/CMAR.S259393

Effect of the Up-Regulation of Circular RNA Hsa_circ_0069767 Derived from C-KIT on the Biological Behavior of Multiple Myeloma Cells

Cancer Manag Res. 2020 Nov 6:12:11321-11331. doi: 10.2147/CMAR.S259393. eCollection 2020.

Authors

Fang Chen^{1

2}, Xiaohui Wang¹, Shuang Fu¹, Shaokun Wang¹, Yu Fu¹, Zhuogang Liu², Jihong Zhang¹

Affiliations

¹ Hematology Laboratory, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China.
² Department of Hematology, Shengjing Hospital of China Medical University, Shenyang 110022, People's Republic of China.

Abstract

Purpose: Multiple myeloma (MM) is an incurable disease. This study focused on the expression of circular RNA circ_0069767 in MM and its influence on prognosis, in order to provide a potential target.

Patients and methods: Totally 66 MM patients participated in this research. Using RT-PCR method to determine the expression level of circ_0069767 in 66 sorted samples from multiple myeloma patients and 21 normal control bone marrow samples, Kaplan-Meier was applied for survival analysis. We constructed stable over-expressing circ_0069767 and silenced circ_0069767 cell lines and used MTS experiment to detect cell viability, transwell experiment to detect cell migration and invasion ability and flow cytometry to detect cell apoptosis. Dual luciferase experiment, qRT-PCR experiment and Western blot were used to explore miRNA and downstream genes.

Results: The expression of circ_0069767 in MM was significantly higher than that of the normal control group. Patients with high expression of circ_0069767 had longer PFS and OS. Cell function experiments showed that overexpression of circ_0069767 in MM cells led to decreased proliferation, migration and invasion, but increased apoptosis; meanwhile, knockdown of circ_0069767 caused opposite biological behaviors. Circ_0069767 by sponging miR-636 in MM cells regulates the expression of K-RAS while the K-RAS gene remained unmutated.

Conclusion: Circ_0069767 plays an antitumor role and its expression can be used as a reliable prognostic indicator for MM patients.

Keywords: circular RNA; multiple myeloma; prognostic factor.

Grants and funding

This research was supported by grants from National Natural Science Foundation of China (Grant No. 81300420) and the Liaoning Province Natural Science Foundation of China (Grant No. 20170540996).