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.

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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