SOX21-AS1 activated by STAT6 promotes pancreatic cancer progression via up-regulation of SOX21

J Transl Med. 2022 Nov 5;20(1):511. doi: 10.1186/s12967-022-03521-5.

Abstract

Background: Pancreatic cancer (PC) is a highly malignant tumor which threatens human's health. Long non-coding RNAs (lncRNAs) are implicated in many cancers, including PC, but their mechanisms in PC have not yet been entirely clarified. We focused on revealing the potential function of lncRNA SOX21-AS1 in PC.

Methods: Functional assays assessed SOX21-AS1 function on PC progression. Bioinformatics analysis, along with mechanism assays were taken to unmask the regulatory mechanism SOX21-AS1 may exert in PC cells.

Results: SOX21-AS1 possessed a high expression level in PC cells. SOX21-AS1 absence suppressed PC cell proliferation, migration, stemness and epithelial-mesenchymal transition (EMT) while elevated cell apoptosis. SOX21-AS1 positively regulated its nearby gene SRY-box transcription factor 21 (SOX21) at post-transcriptional level. Through mechanism assays, we uncovered that SOX21-AS1 sponged SOX21-AS1 to elevate SOX21 mRNA and recruited ubiquitin-specific peptidase 10 (USP10) to deubiquitinate and stabilize SOX21 protein. Moreover, signal transducer and activator of transcription 6 (STAT6) could transcriptionally activate SOX21-AS1 and SOX21 expression.

Conclusions: SOX21-AS1 aggravated the malignant development of PC, which might provide the utility value for PC treatment.

Keywords: Pancreatic cancer; SOX21; SOX21-AS1; STAT6.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • STAT6 Transcription Factor / metabolism
  • Ubiquitin Thiolesterase / genetics
  • Up-Regulation / genetics

Substances

  • STAT6 Transcription Factor
  • RNA, Long Noncoding
  • MicroRNAs
  • STAT6 protein, human
  • USP10 protein, human
  • Ubiquitin Thiolesterase