PRPF19 promotes tongue cancer growth and chemoradiotherapy resistance

Acta Biochim Biophys Sin (Shanghai). 2021 Jul 5;53(7):893-902. doi: 10.1093/abbs/gmab059.

Abstract

Pre-mRNA processing factor 19 (PRPF19) is a multifaceted protein and participates in DNA damage response and pre-mRNA processing. The role of PRPF19 in cancer is unclear. Here, we report that the expression of PRPF19 in human tongue cancer is associated with unfavorable prognosis. Overexpression of PRPF19 promotes while knockdown of PRPF19 inhibits tongue cancer cell migration, proliferation, and tumor growth. Overexpression of PRPF19 increases the resistance of tongue cancer cells to radiation and cisplatin treatment. Furthermore, PRPF19 regulates the expression of solute carrier family 40 member 1 (SLC40A1) and mono-ADP ribosylhydrolase 2 (MACROD2), knockdown of SLC40A1 or MACROD2 decreases the sensitivity of tongue cancer cells to radiation and cisplatin treatment. Thus, our results establish a key role of PRPF19 in tongue cancer growth and chemoradiotherapy resistance, targeting PRPF19 would be an effective therapeutic strategy for tongue cancer, especially for those resistant to chemoradiotherapy.

Keywords: PRPF19; chemoradiotherapy resistance; recurrence; tongue cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Movement* / radiation effects
  • Cell Proliferation* / drug effects
  • Cell Proliferation* / radiation effects
  • Chemoradiotherapy*
  • Cisplatin / pharmacology*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / radiation effects
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Splicing Factors / genetics
  • RNA Splicing Factors / metabolism*
  • Radiation Tolerance* / drug effects
  • Radiation Tolerance* / radiation effects
  • Radiation, Ionizing
  • Tongue Neoplasms* / genetics
  • Tongue Neoplasms* / metabolism
  • Tongue Neoplasms* / pathology
  • Tongue Neoplasms* / therapy
  • Xenograft Model Antitumor Assays

Substances

  • Neoplasm Proteins
  • Nuclear Proteins
  • RNA Splicing Factors
  • DNA Repair Enzymes
  • PRPF19 protein, human
  • Cisplatin