MicroRNA-411-3p motivates methotrexate’s cellular uptake and cytotoxicity via targeting Yin-yang 1 in leukemia cells

  • HuiJing Sun Department of Pharmacy, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China
  • ShuGuang Zhou Department of Pharmacy, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China
  • ZhouSheng Yang Department of Pharmacy, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China
  • MingYu Meng Department of Pharmacy, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China
  • Yan Dai Department of Paediatrics, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China
  • XinYe Li Department of Paediatrics, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China
  • XiaoYu Chen Department of Pharmacy, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning City, Guangxi Zhuang Autonomous Region, 530021, China https://orcid.org/0000-0002-8499-377X

Abstract

This study aimed to figure out how microRNA (miR)-411-3p’s impacts on methotrexate (MTX)’s cellular uptake and cytotoxicity in acute lymphoblastic leukaemia (ALL) CEM-C1 cells by targeting Yin-yang 1 (YY1). miR-411-3p and YY1 were detected by RT-qPCR or Western blot. Intracellular MTX concentration was measured by enzyme-linked immunosorbent assay. Cell viability and apoptosis were evaluated by CCK-8, clonal formation assay, and flow cytometry. Verification of miR-411-3p and YY1’s targeting link was manifested. It came out that miR-411-3p mimic or si-YY1 elevated intracellular MTX, MTX-induced cytotoxicity and apoptosis rate in CEM-C1. However, the inverse results were noticed in cells introduced with miR-411-3p inhibitor or oe-YY1. Meanwhile, it was found that cell relative luciferase activity was reduced after co-transfection of miR-411-3p mimic with YY1-WT, indicating that miR-411-3p targeted YY1. Elevation of YY1 could turn around elevating miR-411-3p’s impacts on MTX’s cellular uptake and cytotoxicity in CEM-C1 cells. These findings convey that miR-411-3p motivated MTX’s cellular uptake and cytotoxic impacts via targeting YY1 in leukemia cells. This study is helpful for learning about the mechanisms underlying MTX responses in ALL patients.

Published
2023-09-19
Section
Articles