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Suppressive effects of RASAL2 on renal cell carcinoma via SOX2/ERK/p38 MAPK pathway

Sen Wang1, Xiaomin Hao2, Sai He3

  • 1Department of Urinary Surgery, Shaanxi Friendship Hospital, Xi'an, Shaanxi 710068, P.R. China.

Experimental and Therapeutic Medicine
|October 23, 2020
PubMed

Insights

RASAL2 acts as a tumor suppressor in metastatic renal cell carcinoma (RCC). Its downregulation correlates with poor prognosis, and restoring RASAL2 inhibits RCC cell viability, migration, and invasion.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Metastatic renal cell carcinoma (RCC) presents a significant clinical challenge with a poor prognosis.
  • Ras protein activator like 2 (RASAL2) is recognized as a tumor suppressor in various cancers.

Purpose of the Study:

  • To investigate the role and mechanism of RASAL2 in the development and progression of RCC.
  • To explore RASAL2 as a potential therapeutic target for RCC.

Main Methods:

  • Quantitative PCR, Western blot, and immunohistochemistry to assess RASAL2 expression in RCC tissues and cells.
  • Cell Counting Kit-8, BrdU staining, and Transwell assays to evaluate cell viability, invasion, and migration.
  • Experiments involving RASAL2 overexpression and knockdown in RCC cells to determine functional effects.

Main Results:

  • RASAL2 expression was significantly downregulated in RCC tissues and negatively correlated with pathological grade.
  • RASAL2 overexpression reduced RCC cell viability, invasion, and migration, while inhibiting Sox2 expression and ERK1/2/p38 MAPK activation.
  • RASAL2 knockdown demonstrated opposite effects, increasing cell viability, migration, and invasion, linked to SOX2/ERK1/2/p38 MAPK signaling activation.

Conclusions:

  • RASAL2 functions as a tumor suppressor in RCC by inhibiting the SOX2/ERK1/2/p38 MAPK signaling pathway.
  • RASAL2 holds potential as a therapeutic target for novel intervention strategies in metastatic renal cell carcinoma.
Keywords:
extracellular signal-regulated kinaseinvasionmigrationp38 mitogen-activated protein kinaseras protein activator like 2renal cell carcinoma

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