SALIS transcriptionally represses IGFBP3/Caspase-7-mediated apoptosis by associating with STAT5A to promote hepatocellular carcinoma

Cell Death Dis. 2022 Jul 23;13(7):642. doi: 10.1038/s41419-022-05094-z.

Abstract

Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer and the second most fatal cancer in the world despite the great therapeutic advances in the past two decades, which reminds us of the gap in fully understanding the oncogenic mechanism of HCC. To explore the key factors contributing to the progression of HCC, we identified a LncRNA, termed SALIS (Suppression of Apoptosis by LINC01186 Interacting with STAT5A), functions in promoting the proliferation, colony formation, migration and invasion while suppressing apoptosis in HCC cells. Mechanistic study indicated SALIS physically associates with transcription factor STAT5A and binds to the promoter regions of IGFBP3 and Caspase-7 to transcriptionally repress their expression and further inhibit apoptosis. Our findings identified SALIS as an oncogene to promote HCC by physically binding with STAT5A to inhibit the expression of pro-apoptotic IGFBP3 and Caspase-7, which suggests novel therapeutic targets for HCC treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Liver Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism
  • Tumor Suppressor Proteins / metabolism

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • RNA, Long Noncoding
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Tumor Suppressor Proteins
  • Caspase 7