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Published on: March 15, 2024
Inhibition of MID1IP1 induces ferroptosis and suppresses c-Myc expression in colorectal cancer cell
Je Joung Oh1, Yu Jin Lee1, Yeo Jeong Han1
1College of Korean Medicine, Kyung Hee University, Seoul, 02447, Korea.
Background:
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.
Insights
Midline 1 Interacting Protein 1 (MID1IP1) promotes colorectal cancer (CRC) survival by stabilizing c-Myc and preventing ferroptosis. Targeting MID1IP1 may offer new therapeutic strategies for CRC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) is a leading global cancer diagnosis.
- Drug resistance and metastasis remain significant challenges in CRC treatment.
- Midline 1 Interacting Protein 1 (MID1IP1) expression correlates with tumor growth via c-Myc.
Purpose of the Study:
- Investigate MID1IP1's role in CRC metabolic reprogramming.
- Determine MID1IP1's effect on ferroptosis and cell migration in CRC.
- Explore the link between MID1IP1, c-Myc, and CRC progression.
Main Methods:
- MID1IP1 was silenced in HCT116 cells using siRNA.
- Assays included colony formation, Western blotting, ROS measurement, and wound healing.
- Proteins assessed included c-Myc, ferroptosis markers, glycolytic enzymes, and EMT markers.
Main Results:
- MID1IP1 knockdown reduced cell growth and c-Myc stability.
- Glycolysis and ferroptosis-protective proteins decreased, leading to ROS accumulation and ferroptosis.
- Cell migration was inhibited, with associated changes in EMT markers.
Conclusions:
- MID1IP1 enhances CRC cell survival by stabilizing c-Myc and inhibiting ferroptosis.
- MID1IP1 influences CRC cell migration and metabolic reprogramming.
- MID1IP1 presents a potential novel biomarker and therapeutic target for CRC.
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