MSRB3 promotes the progression of clear cell renal cell carcinoma via regulating endoplasmic reticulum stress

Pathol Res Pract. 2020 Feb;216(2):152780. doi: 10.1016/j.prp.2019.152780. Epub 2019 Dec 2.

Abstract

Background: Renal cancer represents about 3 % of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. Methionine sulfoxide reductase B3 (MSRB3) is a protein repair enzyme that specifically catalyzes the reduction of methionine-R-sulfoxide residues and has an antioxidant function. However, MSRB3's role in ccRCC is still obscure.

Methods: Immunohistochemical staining and Real-time PCR were used to compare the expression level of MSRB3 in ccRCC tissues and adjacent tissues. Western blot was used to detect the expression of MSRB3 in cell lines. Chi-square test were applied to evaluate the potential of MSRB3 to function as a cancer biomarker. RNA interference was used to inhibit MSRB3 expression in ccRCC cells, followed by detecting cell proliferation, apoptosis, migration and invasion. The markers of endoplasmic reticulum stress were then detected by western blot.

Results: In this study, we validated that MSRB3 was significantly up-regulated in ccRCC samples and cell lines. It was also demonstrated that the up-regulation of MSRB3 was associated with several clinicopathologic features. Knockdown of MSRB3 remarkably arrested the proliferation, migration and invasion, while promoted apoptosis, and induced the changes of markers of endoplasmic reticulum stress.

Conclusion: In conclusion, we demonstrated that MSRB3 was an oncogene of ccRCC associated with patients' pathological characteristics and modulated endoplasmic reticulum stress of cancer cells.

Keywords: Endoplasmic reticulum stress; MSRB3; Metastasis; Proliferation; ccRCC.

MeSH terms

  • Apoptosis
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / enzymology*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Endoplasmic Reticulum Stress*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / enzymology*
  • Kidney Neoplasms / pathology
  • Male
  • Methionine Sulfoxide Reductases / genetics
  • Methionine Sulfoxide Reductases / metabolism*
  • Middle Aged
  • Neoplasm Metastasis
  • RNA Interference

Substances

  • Methionine Sulfoxide Reductases
  • MSRB3 protein, human