DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p

World J Gastroenterol. 2020 Apr 21;26(15):1745-1757. doi: 10.3748/wjg.v26.i15.1745.

Abstract

Background: The incidence and mortality rates of pancreatic carcinoma (PC) are rapidly increasing worldwide. Long noncoding RNAs (lncRNAs) play critical roles during PC initiation and progression. Since the lncRNA DNAH17-AS1 is highly expressed in PC, the regulation of DNAH17-AS1 in PC was investigated in this study.

Aim: To investigate the expression and molecular action of lncRNA DNAH17-AS1 in PC cells.

Methods: The PC expression data for the lncRNA DNAH17-AS1 was downloaded from The Cancer Genome Atlas database and used to examine its profile. Western blot and reverse transcription-quantitative PCR were employed to assess protein and mRNA expression. A subcellular fractionation assay was used to determine the location of DNAH17-AS1 in cells. In addition, the regulatory effects of DNAH17-AS1 on miR-432-5p, PPME1, and tumor activity were investigated using luciferase reporter assay, MTT viability analysis, flow cytometry, and transwell migration analysis.

Results: DNAH17-AS1 was upregulated in PC cells and was associated with aggressive tumor behavior and poor prognosis for patients. Silencing DNAH17-AS1 promoted the apoptosis and reduced the viability, invasion, and migration of PC cells. In addition, DNAH17-AS1 served as a PC oncogene by downregulating miR-432-5p which normally directly targeted PPME1 to downregulate its expression.

Conlusion: DNAH17-AS1 functions in PC as a tumor promoter by regulating the miR-432-5p/PPME1 axis. This finding may provide new insights for PC prognosis and therapy.

Keywords: DNAH17-AS1; Long noncoding RNAs; MiR-432-5p; Molecular mechanism; PPME1; Pancreatic carcinoma.

Publication types

  • Observational Study

MeSH terms

  • Apoptosis / genetics
  • Carboxylic Ester Hydrolases / genetics*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pancreas / pathology
  • Pancreas / surgery
  • Pancreatectomy
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / surgery
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Up-Regulation

Substances

  • MIRN432 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Carboxylic Ester Hydrolases
  • protein phosphatase methylesterase-1