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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
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DRAM1 plays a tumor suppressor role in clear cell renal cell carcinoma through modulating Akt signaling

Qingyan Feng1, Meijuan Cheng1, Jingjing Jin1

  • 1Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China.

Acta Histochemica
|March 17, 2022
PubMed
Abstract

Insights

DNA damage-regulated autophagy modulator 1 (DRAM1) suppresses clear cell renal cell carcinoma (ccRCC) progression by inhibiting cell proliferation, migration, and invasion. Reduced DRAM1 expression in ccRCC patients indicates a poorer prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Clear cell renal cell carcinoma (ccRCC) is a prevalent malignancy globally.
  • DNA damage-regulated autophagy modulator 1 (DRAM1) is implicated in apoptosis and tumor progression.
  • The specific role of DRAM1 in ccRCC remains largely unexplored.

Purpose of the Study:

  • To investigate the function and prognostic significance of DRAM1 in clear cell renal cell carcinoma.
  • To elucidate the molecular mechanisms underlying DRAM1's effect on ccRCC progression.

Main Methods:

  • Immunohistochemistry and bioinformatics databases were used to assess DRAM1 expression and prognosis in ccRCC.
  • Cellular assays (CCK-8, wound-healing, Transwell, TUNEL, flow cytometry) evaluated proliferation, migration, invasion, and apoptosis.
  • Western blotting analyzed protein expression, including DRAM1, apoptosis markers (Bax, Bcl2), Akt signaling pathway, and epithelial-mesenchymal transition (EMT) markers.

Main Results:

  • DRAM1 expression was significantly decreased in ccRCC tissues, correlating with shorter patient survival.
  • Overexpression of DRAM1 suppressed ccRCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
  • DRAM1 enhanced ccRCC cell apoptosis and inactivated the Akt signaling pathway by reducing Akt phosphorylation, reversing oncogenic Akt-driven functions.

Conclusions:

  • DRAM1 functions as a tumor suppressor in ccRCC by inactivating the Akt signaling pathway.
  • DRAM1 holds potential as a valuable prognostic biomarker for clear cell renal cell carcinoma.
Keywords:
Akt signaling pathwayApoptosisClear cell renal cell carcinoma (ccRCC)DNA-damage regulated autophagy modulator 1 (DRAM1)Prognosis

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