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DUSP9 Suppresses Proliferation and Migration of Clear Cell Renal Cell Carcinoma via the mTOR Pathway
Jing Luo1, Xing Luo1, Xin Liu1
1Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, People's Republic of China.
Background:
Clear cell renal cell carcinoma (ccRCC) is one of the most common urologic tumors. However, the carcinogenic mechanism of ccRCC remains unclear. This study aimed to investigate the effects of dual specificity phosphatase 9 (DUSP9) in ccRCC.
Methods:
Cell proliferation and migration abilities were detected by Cell Counting kit-8, wound-healing (scratch) assay and transwell assay. The expression of mRNA in ccRCC was measured by qPCR. Western blot and immunohistochemical staining were used for protein expression. In addition, nude mouse xenograft experiment establishes an in vivo model to detect the inhibitory effect of DUSP9 on tumor proliferation.
Results:
DUSP9 was significantly down-regulated in both ccRCC cell lines and ccRCC tissues compared to that in non-cancer cell lines and normal tissues. Besides, DUSP9 suppressed proliferation and migration of ccRCC cell lines in vitro. Importantly, the inhibition of tumor growth by DUSP9 was confirmed by xenograft tumor studies. And DUSP9 could inhibit both phosphorylation of mTOR and expression of its pathway-associated proteins Sox2, c-Myc, and HIF-1α, which are involved in cell proliferation and migration.
Conclusion:
Taken together, our results uncovered DUSP9 as a tumor suppressor in ccRCC, acting by regulating cell proliferation and migration via the mTOR pathway.
Insights
Dual specificity phosphatase 9 (DUSP9) acts as a tumor suppressor in clear cell renal cell carcinoma (ccRCC). Lower DUSP9 levels correlate with ccRCC, and its restoration inhibits tumor growth and migration by affecting the mTOR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Clear cell renal cell carcinoma (ccRCC) is a prevalent urologic malignancy with incompletely understood carcinogenic mechanisms.
- Investigating novel molecular players is crucial for understanding ccRCC pathogenesis.
Purpose of the Study:
- To elucidate the role and mechanism of dual specificity phosphatase 9 (DUSP9) in clear cell renal cell carcinoma.
- To determine if DUSP9 functions as a tumor suppressor in ccRCC.
Main Methods:
- Assessed cell proliferation and migration using Cell Counting kit-8, scratch, and Transwell assays.
- Quantified mRNA and protein expression via qPCR, Western blot, and immunohistochemistry.
- Utilized a nude mouse xenograft model to evaluate DUSP9's in vivo anti-tumor effects.
Main Results:
- DUSP9 expression was significantly reduced in ccRCC cell lines and tissues compared to normal controls.
- DUSP9 suppressed ccRCC cell proliferation and migration in vitro.
- In vivo studies confirmed DUSP9's inhibition of tumor growth.
- DUSP9 downregulated mTOR phosphorylation and key pathway proteins (Sox2, c-Myc, HIF-1α) involved in proliferation and migration.
Conclusions:
- DUSP9 functions as a tumor suppressor in ccRCC.
- DUSP9 regulates ccRCC cell proliferation and migration through the mTOR signaling pathway.
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