Volume 61, Issue 3 pp. 301-310
RESEARCH ARTICLE

MiR-15a-3p regulates ferroptosis via targeting glutathione peroxidase GPX4 in colorectal cancer

Liurong Liu

Liurong Liu

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Department of General Surgery, Yancheng Third People's Hospital, Yancheng, Jiangsu, China

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Huihui Yao

Huihui Yao

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Xin Zhou

Xin Zhou

Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Junjie Chen

Junjie Chen

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Guoliang Chen

Guoliang Chen

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Xinyu Shi

Xinyu Shi

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Guanting Wu

Guanting Wu

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

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Guoqiang Zhou

Guoqiang Zhou

Department of Gastrointestinal Surgery, Changshu No. 2 Hospital, Suzhou, Jiangsu, China

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Songbing He

Corresponding Author

Songbing He

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China

Correspondence Songbing He, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.

Email: [email protected].

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First published: 02 November 2021
Citations: 62

Liurong Liu and Huihui Yao contributed equally to this work.

Abstract

Colorectal cancer (CRC) is the second most common cancer-related deaths throughout the world. Ferroptosis is a recently regulated form of cell death, lately gains attention. MicroRNA-15a-3p (miR-15a-3p) plays a regulatory role in various kinds of cancers. However, the role of miR-15a-3p in cellular ferroptosis is still unclear. Here, we aimed to clarify whether miR-15a-3p could regulate the ferroptosis of CRC. Here we identified miR-15a-3p positively regulates ferroptosis via directly targeting glutathione peroxidase glutathione peroxidase 4 (GPX4) in CRC. Overexpression of miR-15a-3p repressed GPX4 through binding to the 3′-untranslated region of GPX4, resulting in increased reactive oxygen species level, intracellular Fe2+ level, and malondialdehyde accumulation in vitro and in vivo. Correspondingly, suppression of miR-15a-3p reduced the sensitivity of CRC cells to erastin and GPX4. Taken together, these data demonstrate that miR-15a-3p regulates ferroptosis through targeting GPX4 in CRC cells, illustrating the novel role of microRNA in ferroptosis.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

DATA AVAILABILITY STATEMENT

The data used in the current study are available from the corresponding author on reasonable request.

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