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Inhibition of MID1IP1 induces ferroptosis and suppresses c-Myc expression in colorectal cancer cell

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Abstract

Background

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Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Despite treatment advances, CRC still requires novel strategies to overcome drug resistance and metastasis. Midline 1 Interacting Protein 1 (MID1IP1) is highly expressed in cancers and promotes tumor growth through c-Myc-mediated ribosomal protein regulation. We hypothesized that MID1IP1 contributes to CRC progression via c-Myc and ferroptosis.

Objective

To investigate how MID1IP1 affects metabolic reprogramming, ferroptosis, and migration in CRC.

Methods

MID1IP1 was silenced in HCT116 cells using siRNA. Colony formation assays evaluated growth. Western blotting assessed c-Myc, ferroptosis-related proteins, glycolytic enzymes, and EMT markers. Intracellular ROS was measured with a fluorescence probe, and a ferroptosis inhibitor confirmed ferroptotic cell death. Immunofluorescence detected c-Myc and PKM2, while wound healing assays evaluated migration.

Results

MID1IP1 knockdown reduced cell growth and c-Myc stability, lowering glycolysis-related protein expression. GPX4 and other ferroptosis-protective proteins decreased, resulting in ROS accumulation and ferroptosis. Migration was inhibited, with altered EMT marker expression.

Conclusion

MID1IP1 promotes CRC cell survival by stabilizing c-Myc and preventing ferroptosis, while also influencing migration. These findings suggest that MID1IP1 may serve as a novel biomarker and therapeutic target in CRC.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MIST) (No. RS-2023-00209169).

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Author notes

  1. Je Joung Oh, Yu Jin Lee and Yeo Jeong Han have contributed equally to this work.

Authors and Affiliations

  1. College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea

    Je Joung Oh, Yu Jin Lee, Yeo Jeong Han, Jinbong Park, Woojin Kim & Ji Hoon Jung

  2. Faculty of Pharmaceutical Sciences, Nihon Pharmaceutical University, Tokyo, 113-0034, Japan

    Yui Sasaki

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  1. Je Joung Oh
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Contributions

J.J.O., Y.J.L. and Y.J.H. performed experiments; J.J.O., Y.J.L. and Y.J.H contributed to data analysis; J.H.J. and J.J.O. Y.J.L., Y.J.H. conceived and designed experiments; J.J.O., Y.J.L., Y.J.H. and J.H.J. wrote and edited the paper; J.H.J, J.J.O., Y.J.L., Y.J.H., S-Y.L. and J.C reviewed and edited the paper; all authors read and agreed to the published version of the manuscript.

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Correspondence to Ji Hoon Jung.

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Oh, J.J., Lee, Y.J., Han, Y.J. et al. Inhibition of MID1IP1 induces ferroptosis and suppresses c-Myc expression in colorectal cancer cell. Genes Genom (2025). https://doi.org/10.1007/s13258-025-01717-9

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