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Updated: Dec 21, 2025

Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
miR-429-CRKL axis regulates clear cell renal cell carcinoma malignant progression through SOS1/MEK/ERK/MMP2/MMP9
Jinxia Wang1, Chengyi Wang2, Qian Li3
1Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China; Department of Biochemistry, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
Abstract:
The pathogenesis and tumorigenesis of clear cell renal cell carcinoma (ccRCC) remain unclear. The deregulations of miR-429, a member of miR-200 family, and v-crk sarcoma virus CT10 oncogene homologue (avian)-like (CRKL), an adaptor protein of CRK family, are involved in the development, metastasis and prognosis of various cancers. Current study aimed to demonstrate the differential expressions of miR-429 and CRKL with their correlationship and molecular regulation mechanism in ccRCC malignancy. miR-429 and CRKL separately showed suppressing and promoting effects in ccRCC. Lower miR-429 expression and higher CRKL expression were negatively correlated in surgical cancerous tissues by promoting the advance of ccRCC. By binding to the 3'-UTR of CRKL, miR-429 reversely regulated CRKL for its functionalities in ccRCC cells. CRKL knockdown and overexpression separately decreased and increased the in vitro migration and invasion of 786-O cells, which were consistent with the influences of miR-429 overexpression and knockdown on 786-O through respectively downregulating and upregulating CRKL via SOS1/MEK/ERK/MMP2/MMP9 pathway. The enhancements of CRKL expression, migration and invasion abilities and SOS1/MEK/ ERK/MMP2/MMP9 activation induced by TGF-β stimulation in 786-O cells could be antagonized by miR-429 overexpression. Exogenous re-expression of CRKL abrogated miR-429 suppression on the migration and invasion of 786-O cells. Collectively, miR-429 deficiency negatively correlated with CRKL overexpression promoted the aggressiveness of cancer cells and advanced the clinical progression of ccRCC patients. miR-429-CRKL axial regulation provides new clues to the fundamental research, diagnosis and treatment of ccRCC.
Insights
MicroRNA-429 (miR-429) suppresses clear cell renal cell carcinoma (ccRCC) by downregulating CRKL. Low miR-429 and high CRKL correlate with advanced ccRCC, offering diagnostic and therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) pathogenesis remains unclear.
- Dysregulation of miR-429 and CRKL is implicated in various cancers.
- Understanding their roles in ccRCC is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate differential expressions of miR-429 and CRKL in ccRCC.
- To explore their correlationship and molecular regulation mechanisms.
- To assess their impact on ccRCC progression and metastasis.
Main Methods:
- Quantitative real-time PCR for miR-429 and CRKL expression analysis.
- Western blotting to assess protein levels.
- In vitro cell migration and invasion assays (786-O cells).
- Luciferase reporter assays to confirm direct binding of miR-429 to CRKL 3'-UTR.
- TGF-β stimulation experiments to mimic tumor microenvironment effects.
Main Results:
- miR-429 expression was lower, while CRKL expression was higher in ccRCC tissues, showing a negative correlation.
- miR-429 directly targeted and downregulated CRKL.
- CRKL overexpression promoted, while knockdown inhibited, cell migration and invasion.
- miR-429 suppressed migration and invasion by downregulating CRKL via the SOS1/MEK/ERK/MMP2/MMP9 pathway.
- miR-429 overexpression antagonized TGF-β-induced enhancement of CRKL expression and cell aggressiveness.
Conclusions:
- miR-429 acts as a tumor suppressor in ccRCC by inhibiting CRKL.
- The miR-429-CRKL axis is a key regulator of ccRCC cell aggressiveness and progression.
- This regulatory axis offers potential targets for ccRCC diagnosis and therapy.
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