FOXM1a Isoform of Oncogene FOXM1 Is a Tumor Suppressor Suppressed by hnRNP C in Oral Squamous Cell Carcinoma

Biomolecules. 2023 Aug 30;13(9):1331. doi: 10.3390/biom13091331.

Abstract

FOXM1 is an oncogenic transcriptional factor and includes several isoforms generated by alternative splicing. Inclusion of alternative exon 9 produces FOXM1a, a transcriptionally inactive isoform. However, the role of FOXM1a in tumorigenesis remains unknown. In addition, the regulatory mechanisms of exon 9 splicing are also unclear. In the present study, we found that overexpression of FOXM1a significantly reduced cell proliferation and colony formation of oral squamous cell carcinoma (OSCC) cell proliferation in vitro. Importantly, OSCC cells with FOXM1a overexpression showed significantly slower tumor formation in nude mice. Moreover, we identified a U-rich exonic splicing suppressor (ESS) which is responsible for exon 9 skipping. Splicing factor heterogeneous nuclear ribonucleoprotein C (hnRNP C) can bind to the ESS and suppress exon 9 inclusion and FOXM1a expression. Silence of hnRNP C also significantly suppresses OSCC cell proliferation. HnRNP C is significantly co-expressed with FOXM1 in cancers. Our study uncovered a novel regulatory mechanism of oncogene FOXM1 expression in OSCC.

Keywords: FOXM1; alternative splicing; hnRNP C; oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Forkhead Box Protein M1* / genetics
  • Forkhead Box Protein M1* / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein Group C* / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein Group C* / metabolism
  • Humans
  • Mice
  • Mice, Nude
  • Mouth Neoplasms* / genetics
  • Oncogenes
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / genetics

Substances

  • Heterogeneous-Nuclear Ribonucleoprotein Group C
  • Protein Isoforms
  • HNRNPC protein, human
  • FOXM1 protein, human
  • Forkhead Box Protein M1

Grants and funding

This research was funded by the National Natural Science Foundation of China, grant 81470741, and the International Scientific Collaboration Project of Hubei Province, grant number 2022EHB036.