MicroRNA-935 Directly Targets FZD6 to Inhibit the Proliferation of Human Glioblastoma and Correlate to Glioma Malignancy and Prognosis

Dainan Zhang; Shunchang Ma; Chuanbao Zhang; Peiliang Li; Beibei Mao; Xiudong Guan; Wenjianlong Zhou; Jiayi Peng; Xi Wang; Shaomin Li; Wang Jia

doi:10.3389/fonc.2021.566492

MicroRNA-935 Directly Targets FZD6 to Inhibit the Proliferation of Human Glioblastoma and Correlate to Glioma Malignancy and Prognosis

Front Oncol. 2021 Mar 12:11:566492. doi: 10.3389/fonc.2021.566492. eCollection 2021.

Authors

Dainan Zhang^{1

2}, Shunchang Ma², Chuanbao Zhang^{1

2

3}, Peiliang Li^{1

4}, Beibei Mao^{1

5}, Xiudong Guan^{1

2}, Wenjianlong Zhou¹, Jiayi Peng¹, Xi Wang¹, Shaomin Li⁶, Wang Jia^{1

2}

Affiliations

¹ Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.
³ Chinese Glioma Genome Atlas Network (CGGA), Beijing, China.
⁴ Department of Neurosurgery, Ditan Hospital, Capital Medical University, Beijing, China.
⁵ Department of Neurosurgery, Shijitan Hospital, Capital Medical University, Beijing, China.
⁶ Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States.

Abstract

MicroRNAs (miRNAs) are involved in human glioblastoma (GB). MiR-935 has been reported to have both tumor-inhibiting and tumorigenesis effects, but its role in GB remains unclear. Because of the high mortality and morbidity associated with the malignancy of GB, a deeper understanding of the molecular crosstalk that occurs in GB is needed to identify new potential targets for treatment. At present, the mechanism of GB at the molecular level is not fully understood. With the aid of bioinformatic analysis, miR-935 was significantly downregulated in GB, and it presented a poorer outcome. In the glioma cell line and in the nude mice model, the miR-935 inhibited cell proliferation by modulating cell circles in vitro and in vivo. Then, the target genes of miR-935 were analyzed by using the online database, and the direct binding was tested with a luciferase analysis. FZD6 was found to be the direct target of miR-935. The effect of miR-935 was recovered by the overexpression of FZD6 in vitro. In addition, the negative correlation of miR-935 and the expression of FZD6 were confirmed in our clinical samples, and the expression of FZD6 has a strong correlation with tumor malignancy and prognosis. This study showed that miR-935 directly inhibited the expression of FZD6 and inhibited the cell proliferation, thereby suppressing the development of GB, suggesting that miR-935 is a cancer suppressor miRNA and may become a prognostic biomarker or a promising potential therapeutic target for human GBs.

Keywords: FZD6; GB; MiR-935; cell proliferation; clinical prognosis.