LncRNA PART1 promotes cell proliferation and inhibits apoptosis of oral squamous cell carcinoma by blocking EZH2 degradation

J Biochem. 2021 Sep 7;169(6):721-730. doi: 10.1093/jb/mvab026.

Abstract

Long non-coding RNAs (lncRNAs) have been considered as novel regulators in oral squamous cell carcinoma (OSCC). Enhancer of zeste homolog 2 (EZH2) can act as an oncogene in OSCC. This study intended to investigate whether lncRNA prostatic androgen-regulated transcription 1 (PART1) can exert its role in OSCC by regulating EZH2. The expression of PART1 in OSCC samples, tumour tissues or OSCC cell lines was detected by qRT-PCR. The proliferation and apoptosis of OSCC cells were detected by CCK-8 and flow cytometry assays, respectively. The expression of PART1 and EZH2 was highly expressed in clinical OSCC tumours and cell lines. The expression level of PART1 was positively correlated to the size, clinical stage and node metastasis of OSCC patients. Functionally, PART1 knockdown inhibited proliferation and facilitated apoptosis of OSCC cells. Mechanically, fused in sarcoma/translocated in liposarcoma (FUS) interacted with PART1 and EZH2. In addition, PART1 knockdown reduced the mRNA expression of EZH2, which was offset by FUS overexpression. The overexpression of FUS abrogated the effects of PART1 silence on proliferation and apoptosis of OSCC cells. The in vivo experiment revealed that PART1 knockdown inhibited tumour growth of OSCC cells in nude mice. This study indicated that PART1 exerts a carcinogenic role in OSCC by enhancing the stability of EZH2 protein.

Keywords: enhancer of zeste homolog 2; fused in sarcoma/translocated in liposarcoma; lncRNA PART1; oral squamous cell carcinoma.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Proliferation
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Prognosis
  • RNA, Untranslated / genetics*
  • Survival Rate
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • PART-1 RNA, human
  • RNA, Untranslated
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein