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MITD1 Deficiency Suppresses Clear Cell Renal Cell Carcinoma Growth and Migration by Inducing Ferroptosis through the
Ye Zhang1, Yanze Li1, Qiangmin Qiu1
1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC), the major histopathological subtype of renal cancer, is sensitive to ferroptosis. MIT-domain containing protein 1 (MITD1) has been reported to play an important role in hepatocellular carcinoma, while it remains unclear whether MITD1 is involved in ccRCC. Based on available data in The Cancer Genome Atlas, we found the expression of MITD1 increased through bioinformatics analysis and high MITD1 expression suggests a poor prognosis. And we validated that MITD1 expressed significantly in ccRCC through Western blot analysis. Then, we further compared the proliferation and migration capacity of ccRCC before and after MITD1 knockdown and further explored the effect of MITD1 knockdown on ferroptosis. The results indicated that MITD1 knockdown inhibited ccRCC cell proliferation and migration and induced ferroptosis in ccRCC. Furthermore, we found and analyzed the key molecule TAZ which was involved in ferroptosis caused by MITD1 knockdown. Subsequent overexpression experiments demonstrated that MITD1 knockdown induced ferroptosis and suppressed tumor growth and migration through the TAZ/SLC7A11 pathway. In summary, our study revealed the role of MITD1 in the ferroptosis of ccRCC and provided a novel target for ccRCC treatment.
Insights
MIT-domain containing protein 1 (MITD1) promotes clear cell renal cell carcinoma (ccRCC) progression. Knocking down MITD1 inhibits ccRCC growth and migration by inducing ferroptosis via the TAZ/SLC7A11 pathway, offering a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Clear cell renal cell carcinoma (ccRCC) is sensitive to ferroptosis.
- The role of MIT-domain containing protein 1 (MITD1) in ccRCC is currently unknown.
- MITD1 is implicated in hepatocellular carcinoma progression.
Purpose of the Study:
- To investigate the role of MITD1 in ccRCC.
- To determine if MITD1 affects ferroptosis in ccRCC.
- To identify potential therapeutic targets for ccRCC.
Main Methods:
- Bioinformatic analysis of The Cancer Genome Atlas (TCGA) data.
- Western blot analysis for MITD1 expression validation.
- Cell proliferation and migration assays after MITD1 knockdown.
- Investigation of the TAZ/SLC7A11 pathway.
Main Results:
- MITD1 expression is upregulated in ccRCC and associated with poor prognosis.
- MITD1 knockdown inhibits ccRCC cell proliferation and migration.
- MITD1 knockdown induces ferroptosis in ccRCC cells.
- The TAZ/SLC7A11 pathway mediates the effects of MITD1 knockdown on ferroptosis.
Conclusions:
- MITD1 promotes ccRCC progression and its knockdown induces ferroptosis.
- MITD1 knockdown suppresses tumor growth and migration through the TAZ/SLC7A11 pathway.
- MITD1 represents a potential novel therapeutic target for ccRCC treatment.
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