Loss of SELENOF Induces the Transformed Phenotype in Human Immortalized Prostate Epithelial Cells

Abstract

SELENOF is a member of the class of selenoproteins in which the amino acid selenocysteine is co-translationally inserted into the elongating peptide in response to an in-frame UGA codon located in the 3′-untranslated (3′-UTR) region of the SELENOF mRNA. Polymorphisms in the 3′-UTR are associated with an increased risk of dying from prostate cancer and these variations are functional and 10 times more frequent in the genomes of African American men. SELENOF is dramatically reduced in prostate cancer compared to benign adjacent regions. Using a prostate cancer tissue microarray, it was previously established that the reduction of SELENOF in the cancers from African American men was significantly greater than in cancers from Caucasian men. When SELENOF levels in human prostate immortalized epithelial cells were reduced with an shRNA construct, those cells acquired the ability to grow in soft agar, increased the ability to migrate in a scratch assay and acquired features of energy metabolism associated with prostate cancer. These results support a role of SELENOF loss in prostate cancer progression and further indicate that SELENOF loss and genotype may contribute to the disparity in prostate cancer mortality experienced by African American men.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 07, 2021
Source ID
10.3390/ijms222112040

Entities

People

  • Alan M Diamond
  • Heidi Wang
  • Irida Kastrati
  • Karen S Sfanos
  • Lenny K. Hong
  • Li Ping
  • Maria Sverdlov
  • Mostafa Elhodaky
  • Ryan Deaton
  • Shrinidhi Kadkol

Organizations

  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Molecular Genetics
  • Molecular and genetic basis of cancer.
  • Women's Health and Cancer Risk Research: African American Women and Pregnancy Outcomes.