miR-545 promotes colorectal cancer by inhibiting transferring in the non-normal ferroptosis signaling

In 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 Fe levels were measured after treatment with the ferroptosis inducers Eradicator of Ras and S...

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Veröffentlicht in:Aging (Albany, NY.) NY.), 2021-12, Vol.13 (24), p.26137-26147
Hauptverfasser: Zheng, Sixin, Hu, Lingling, Song, Qingwen, Shan, Yuqiang, Yin, Guang, Zhu, Hanzhang, Kong, Wencheng, Zhou, Chunhua
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Sprache:eng
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Zusammenfassung:In 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 Fe 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 Fe 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 Fe levels in HT-29 and HCT-116 cells, thereby inducing CRC cell death. An 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.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.203801