circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis

Fei Liu; Yang Sang; Yang Zheng; Lina Gu; Lingjiao Meng; Ziyi Li; Yuyang Dong; Zishuan Wei; Cuizhi Geng; Meixiang Sang

doi:10.3390/cancers14235862

circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis

Cancers (Basel). 2022 Nov 28;14(23):5862. doi: 10.3390/cancers14235862.

Authors

Fei Liu¹, Yang Sang², Yang Zheng¹, Lina Gu¹, Lingjiao Meng¹, Ziyi Li¹, Yuyang Dong¹, Zishuan Wei¹, Cuizhi Geng³, Meixiang Sang¹

Affiliations

¹ Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China.
² Laboratory Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China.
³ Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China.

Abstract

Circular RNA (circRNA), a type of non-coding RNA, has received a great deal of attention with regard to the initiation and progression of tumors. However, the molecular mechanism and function of circRNAs in breast cancer (BC) remain unclear. In the current study, we discovered that hsa_circ_0028899 (also called circRNF10) was significantly reduced in BC tissues, and a higher level of circRNF10 was markedly related to a favorable prognosis. The results of CCK8, colony formation, Transwell, ELISA, and NK cell-mediated cytotoxicity assays indicated that increased circRNF10 expression could significantly repress the proliferation, invasion, and migration of BC cells and enhance the killing efficiency of NK cells against BC cells. According to these biological functions, the possible role and molecular mechanism of circRNF10 in BC cells were further investigated. We used bioinformatics prediction tools to predict circRNF10-bound miRNAs, which were verified by many experimental studies, including FISH, luciferase reporter assays, RIP, and Western blots. These data suggest that circRNF10 serves as a molecular sponge for miR-934 to further regulate PTEN expression and PI3k/Akt/MICA signaling in vitro and tumor growth in vivo. Altogether, these findings reveal that circRNF10 functions as a novel anti-oncogene in BC via sponging miR-934 and suppressing the PI3K/Akt/MICA pathway.

Keywords: NK; PTEN; breast cancer; circRNF10; miR-934.

Grants and funding

This study was funded by the Hebei Provincial Health Department (Grant No. 20190088), the Key Program of Hebei Natural Science Foundation for Precision Medicine (H2020206199), and thehe Hebei Provincial Department of Education’s postgraduate innovation ability training funding project.