Int J Biol Sci 2021; 17(5):1178-1190. doi:10.7150/ijbs.57783 This issue

Research Paper

CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression

Zhi Li1*, Hai-Yan Yang1*, Xin-Yuan Dai1*, Xu Zhang1, Yu-Zhou Huang1, Liang Shi1✉, Ji-Fu Wei2✉, Qiang Ding1✉

1. Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, P.R. China.
2. Research Division of Clinical Pharmacology, the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, P.R. China.
*These authors equally contributed to the work.

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Citation:
Li Z, Yang HY, Dai XY, Zhang X, Huang YZ, Shi L, Wei JF, Ding Q. CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression. Int J Biol Sci 2021; 17(5):1178-1190. doi:10.7150/ijbs.57783. Available from https://www.ijbs.com/v17p1178.htm

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Abstract

Graphic abstract

Growing evidence indicates N6-methyladenosine (m6A) has biological function in oncogenesis. METTL3, the catalytic component, is the most important part of methyltransferase complex and plays a crucial role in cancers. However, the biological function of circRNAs derived from METTL3 in breast cancer and the underlying molecular mechanism remains unclear. Herein, we report circMETTL3, which has not been explored in breast cancer, and it is markedly upregulated in breast cancer. Moreover, we uncovered that circMETTL3 could facilitate cell proliferation, migration and invasion in breast cancer. Mechanism investigation showed that circMETTL3 might act as a competing endogenous RNA (ceRNA) of miR-31-5p and upregulate its target cyclin-dependent kinases (CDK1). Moreover, m6A modification of circMETTL3 might affect its expression. Taken together, our results elucidate that circMETTL3 promotes breast cancer progression through circMETTL3/miR-31-5p/CDK1 axis. Moreover, METTL3, the host gene of circMETTL3, may regulate circMETTL3 expression in an m6A-dependent manner, while circMETTL3 has no effect on METTL3 expression, providing a new relationship between the circRNA and the corresponding host gene. Thus, it may serve as a new therapeutic target for breast cancer.

Keywords: circMETTL3, miR-31-5p, CDK1, N6-methyladenosine, breast cancer