miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway

Jingyun Zhao; Leilei Liu; Wei Zhao; Cuiting Lv; Na Zhang; Xinzhuan Jia; Zhengmao Zhang

doi:10.1515/med-2023-0729

miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway

Open Med (Wars). 2023 Jun 9;18(1):20230729. doi: 10.1515/med-2023-0729. eCollection 2023.

Authors

Jingyun Zhao¹, Leilei Liu², Wei Zhao³, Cuiting Lv¹, Na Zhang¹, Xinzhuan Jia¹, Zhengmao Zhang⁴

Affiliations

¹ Department of Reproductive Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
² Department of Obstetrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
³ Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
⁴ Department of Gynecology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China.

Abstract

The miR-141-3p has been reported to participate in regulating autophagy and tumor-stroma interactions in ovarian cancer (OC). We aim to investigate whether miR-141-3p accelerates the progression of OC and its effect on macrophage 2 polarization by targeting the Kelch-like ECH-associated protein1-Nuclear factor E2-related factor2 (Keap1-Nrf2) pathway. SKOV3 and A2780 cells were transfected with miR-141-3p inhibitor and negative control to confirm the regulation of miR-141-3p on OC development. Moreover, the growth of tumors in xenograft nude mice treated by cells transfected with miR-141-3p inhibitor was established to further testify the role of miR-141-3p in OC. The expression of miR-141-3p was higher in OC tissue compared with non-cancerous tissue. Downregulation of miR-141-3p inhibited the proliferation, migration, and invasion of ovarian cells. Furthermore, miR-141-3p inhibition also suppressed M2-like macrophage polarization and in vivo OC progression. Inhibition of miR-141-3p significantly enhanced the expression of Keap1, the target gene of miR-141-3p, and thus downregulated Nrf2, while activation of Nrf2 reversed the reduction in M2 polarization by miR-141-3p inhibitor. Collectively, miR-141-3p contributes to tumor progression, migration, and M2 polarization of OC by activating the Keap1-Nrf2 pathway. Inhibition of miR-141-3p attenuates the malignant biological behavior of ovarian cells by inactivating the Keap1-Nrf2 pathway.

Keywords: Keap1; Nrf2; macrophage; miR-141-3p; ovarian cancer; polarization.