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 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

Aging - 13(2021), 24 vom: 26. Dez., Seite 26137-26147

Sprache:

Englisch

Beteiligte Personen:

Zheng, Sixin [VerfasserIn]
Hu, Lingling [VerfasserIn]
Song, Qingwen [VerfasserIn]
Shan, Yuqiang [VerfasserIn]
Yin, Guang [VerfasserIn]
Zhu, Hanzhang [VerfasserIn]
Kong, Wencheng [VerfasserIn]
Zhou, Chunhua [VerfasserIn]

Links:

Volltext

Themen:

Colorectal cancer
Erastin
Ferroptosis
Journal Article
MIR545 microRNA, human
MiR-545
MicroRNAs
Piperazines
Reactive Oxygen Species
Research Support, Non-U.S. Gov't
Transferrin

Anmerkungen:

Date Completed 31.01.2022

Date Revised 31.01.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.18632/aging.203801

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334905885