SPATS2 is positively activated by long noncoding RNA SNHG5 via regulating DNMT3a expression to promote hepatocellular carcinoma progression

PLoS One. 2022 Jan 25;17(1):e0262262. doi: 10.1371/journal.pone.0262262. eCollection 2022.

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors with high mortality worldwide. Spermatogenesis-associated serine-rich 2 (SPATS2) could be a novel diagnostic and prognostic biomarker in HCC. However, the regulatory mechanism of SPATS2 in HCC requires further elucidation. Therefore, the study's objective was to investigate this process in HCC. In this study, we found that SPATS2 is significantly upregulated in HepG2 cells to promote cell growth and migration. SPATS2 is the target transcript of lncRNA SNHG5. SPATS2 positively affects the proliferation and migration of HepG2 cells caused by the higher expression of SNHG5. Mechanistically, we identified that the elevated of SPATS2 was attributed to SNHG5 related hypomethylation of SPATS2. SNHG5 reduced the expression of DNMT3a to suppress the methylation level of SPATS2. Taken together, our results uncover a novel epigenetic regulatory mechanism of lncRNA SNHG5-DNMT3a axis-related SPATS2 expression underlying HCC progression. This may serve as a novel prognostic marker and a promising therapeutic target for the treatment of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement
  • Cell Proliferation
  • DNA Methylation
  • DNA Methyltransferase 3A / metabolism*
  • Disease Progression
  • Epigenesis, Genetic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Polymerase Chain Reaction
  • Proteins / metabolism*
  • RNA, Long Noncoding / metabolism*

Substances

  • DNMT3A protein, human
  • Proteins
  • RNA, Long Noncoding
  • SPATS2 protein, human
  • long non-coding RNA SNHG5, human
  • DNA Methyltransferase 3A

Grants and funding

This work was supported by National Natural Science Foundation of China (CN) (grant Nos. 81660024, 32060156), CSW and PXL received each award. the Natural Science Foundation of Inner Mongolia (Grant Nos. 2020MS08096, 2020MS03007). CSW and PXL received each award.