Long Noncoding RNA CERS6-AS1 Accelerates the Proliferation and Migration of Pancreatic Cancer Cells by Sequestering MicroRNA-15a-5p and MicroRNA-6838-5p and Modulating HMGA1

Pancreas. 2021 Apr 1;50(4):617-624. doi: 10.1097/MPA.0000000000001806.

Abstract

Objectives: As one of the most aggressive human tumors, pancreatic cancer (PC) is accompanied by poor treatment and prognosis. Although emerging evidence has highlighted the importance of long noncoding RNAs in multiple cancers, the specific regulatory roles mostly remain obscure. Our aim was to disclose the role of CERS6 antisense RNA 1 (CERS6-AS1) in PC.

Methods: Quantitative real-time polymerase chain reaction analysis was used to examine the expression of CERS6-AS1 in PC cell lines. Western blot analysis was used to assess the protein levels of high-mobility group AT-hook 1 (HMGA1). Colony formation, 5-ethynyl-20-deoxyuridine, transwell, and wound healing assays were performed to detect the functions of CERS6-AS1 on PC development. In addition, RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were implemented to delve into the regulatory mechanism of CERS6-AS1 in PC.

Results: CERS6-AS1 was significantly upregulated in PC. CERS6-AS1 silence obviously inhibited cell proliferation and migration in PC. Furthermore, CERS6-AS1 sponged microRNA-15a-5p (miR-15a-5p) and microRNA-6838-5p (miR-6838-5p) to regulate HMGA1. Moreover, rescue assays verified that CERS6-AS1 was involved in cell proliferation and migration in PC via targeting miR-15a-5p/miR-6838-5p/HMGA1 axis.

Conclusions: CERS6-AS1 enhanced HMGA1 expression to contribute to the progression of PC by sequestering miR-15a-5p and miR-6838-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • HMGA1a Protein / genetics*
  • HMGA1a Protein / metabolism
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • MicroRNAs / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA, Long Noncoding / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • HMGA1 protein, human
  • MIRN15 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • HMGA1a Protein