The expression of Oct3/4A mRNA and not its isoforms is upregulated by the HPV16 E7 oncoprotein

Mol Biol Rep. 2023 Feb;50(2):981-991. doi: 10.1007/s11033-022-07988-9. Epub 2022 Nov 15.

Abstract

Purpose: Oct3/4 a transcription factor is involved in maintaining the characteristics of cancer stem cells. Oct3/4 can be expressed differentially with respect to the progression of cervical cancer (CC). In addition, Oct3/4 can give rise to three isoforms by alternative splicing of the mRNA Oct3/4A, Oct3/4B and Oct3/4B1. The aim of this study was to evaluate the mRNA expression from Oct3/4A, Oct3/4B and Oct3/4B1 in low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), CC samples, and measure the effect of the HPV16 E7 oncoprotein on the mRNA expression from Oct3/4 isoforms in the C-33A cell line.

Methods: The expression levels of Oct3/4A, Oct3/4B and Oct3/4B1 mRNA were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with LSILs, HSILs and CC. Additionally, C-33A cells that expressed the HPV16 E7 oncoprotein were established to evaluate the effect of E7 on the expression of Oct3/4 mRNA isoforms.

Results: Oct3/4A (p = 0.02), Oct3/4B (p = 0. 001) and Oct3/4B1 (p < 0. 0001) expression is significantly higher in patients with LSIL, HSIL and CC than in woman with non-IL. In the C-33A cell line, the expression of Oct3/4A mRNA in the presence of the E7 oncoprotein increased compared to that in nontransfected C-33A cells.

Conclusion: Oct3/4B and Oct3/4B1 mRNA were expressed at similar levels among the different groups. These data indicate that only the mRNA of Oct3/4A is upregulated by the HPV16 E7 oncoprotein.

Keywords: HPV16 E7 oncoprotein; Oct3/4 isoforms; Oct3/4A; Oct3/4B; Oct3/4B1.

MeSH terms

  • Alternative Splicing / genetics
  • Female
  • Human papillomavirus 16* / genetics
  • Human papillomavirus 16* / metabolism
  • Humans
  • Octamer Transcription Factor-3* / genetics
  • Octamer Transcription Factor-3* / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Uterine Cervical Neoplasms* / metabolism

Substances

  • Protein Isoforms
  • RNA, Messenger
  • Transcription Factors
  • POU5F1 protein, human
  • Octamer Transcription Factor-3