Knockdown of LMNA inhibits Akt/β-catenin-mediated cell invasion and migration in clear cell renal cell carcinoma cells

Cell Adh Migr. 2023 Dec;17(1):1-14. doi: 10.1080/19336918.2023.2260644. Epub 2023 Sep 25.

Abstract

The LMNA gene encoding lamin A/C is amplified in some clear cell renal cell carcinoma (ccRCC) samples. Our data showed that depletion of the tumor suppressor PBRM1 can upregulate lamin A/C levels, and lamin A/C could interact with PBRM1. However, the role of lamin A/C in ccRCC is not yet fully understood. Our functional assays showed that although the proliferation ability was slightly impaired after LMNA depletion, the migration and invasion of ccRCC cells were significantly inhibited. This suppression was accompanied by a reduction in MMP2, MMP9, AKT/p-AKT, and Wnt/β-catenin protein levels. Our data therefore suggest that lamin A/C, as an interaction partner of the tumor suppressor PBRM1, plays a crucial role in tumor invasion and metastasis in ccRCC.

Keywords: LMNA; PBRM1; PI3K/AKT; ccRCC; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / metabolism
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • beta Catenin / genetics

Substances

  • beta Catenin
  • Proto-Oncogene Proteins c-akt
  • Lamin Type A
  • LMNA protein, human

Grants and funding

This work was supported by the grants from National Nature Science Foundation of China [No. 31760321;32360166], Guizhou Province Science and Technology [[2017]1217], Guizhou Province Science and Technology [[2018]1189] and Zunyi Medical University Funding [F-792].