miR-545 promotes colorectal cancer by inhibiting transferring in the non-normal ferroptosis signaling
2021; Impact Journals LLC; Volume: 13; Issue: 24 Linguagem: Inglês
10.18632/aging.203801
ISSN1945-4589
AutoresSixin Zheng, Lingling Hu, Qingwen Song, Yuqiang Shan, Guang Yin, Hanzhang Zhu, Wencheng Kong, Chunhua Zhou,
Tópico(s)RNA modifications and cancer
ResumoIn this study, we examined whether and how miR-545 modulates ferroptosis in colorectal cancer (CRC). HT-29 and HCT-116 human CRC cell viability was examined using a CCK-8 assay and malondialdehyde (MDA) and Fe2+ levels were measured after treatment with the ferroptosis inducers Eradicator of Ras and ST (erastin) and Ras selective lethal 3 (RSL3) with or without miR-545 overexpression or knockdown vectors. Our results demonstrate that miR-545 overexpression inhibited, while miR-545 knockdown further increased, erastin and RSL3-induced upregulation of MDA, reactive oxygen species (ROS), and Fe2+ levels. Similarly, miR-545 overexpression partially reversed, while miR-545 knockdown enhanced, the erastin and RSL3-induced reduction in HT-29 and HCT-116 cell survival rates. Transferrin (TF) was identified as a target gene of miR-545. To determine whether miR-545 suppresses ferroptosis via TF, we overexpressed TF in HT-29 and HCT-116 cells. We found that TF overexpression blocked miR-545-induced changes in ROS, MDA, and Fe2+ levels in HT-29 and HCT-116 cells, thereby inducing CRC cell death. An in vivo assay showed that inhibition of miR-545 decreased tumor growth in nude mice treated with erastin. Together, these findings indicate that miR-545 promotes CRC cell survival by suppressing TF.
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