LINC00319 acts as a microRNA-335-5p sponge to accelerate tumor growth and metastasis in gastric cancer by upregulating ADCY3

Am J Physiol Gastrointest Liver Physiol. 2020 Jan 1;318(1):G10-G22. doi: 10.1152/ajpgi.00405.2018. Epub 2019 Aug 21.

Abstract

Gastric cancer (GC) is one of the most common cancers in the world and remains a heavy burden of health worldwide. Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues and has been identified to be a new molecular target of GC. Long noncoding RNAs have a substantial influence on tumorigenesis and progression of tumors by binding to microRNAs. Therefore, this study is to clarify the mechanism by which LINC00319 sponges micro RNA-335-5p (miR-335-5p) to influence the development of GC. Initially, microarray analysis identified GC-related differentially expressed LINC00319 and ADCY3 for this study. The interaction was confirmed that LINC00319 interacted with miR-335-5p to regulate ADCY3. Next, SGC-7901 cells presenting with the lowest LINC00319 expression and the highest miR-335-5p expression were transfected with LINC00319, miR-335-5p inhibitor, or ADCY3 vector to examine their roles in growth and metastasis of GC cells, which was further ascertained by in vivo experiments. LINC00319 was upregulated and miR-335-5p was downregulated in GC cells. LINC00319 overexpression, miR-335-5p inhibitor, or ADCY3 overexpression was shown to significantly elevate the expression of cyclin-dependent kinase 4 and metastasis associated 1, decrease that of growth arrest-specific 1, and promote tumor growth and metastasis by increasing proliferation and migration and reducing cell apoptosis. Importantly, it was found that overexpressed miR-335-5p exerted its tumor suppressive role in GC through downregulating ADCY3. Collectively, LINC00319 expedited growth and metastasis of GC by upregulating miR-335-5p-mediated ADCY3.NEW & NOTEWORTHY This study is carried out based on in vivo and in vitro studies in mice and gastric cancer (GC) cells with the aim of clarifying the role of LINC00319 on GC growth and metastasis, which associated with micro RNA-335-5p-mediated adenylate cyclase 3. Altogether, we identified LINC00319 to be a potential therapy to treat GC.

Keywords: LINC00319; adenylate cyclase 3; apoptosis; gastric cancer; metastasis; microRNA-335-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Apoptosis
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Databases, Genetic
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Stomach Neoplasms / enzymology*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Tumor Burden
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • MIRN335 microRNA, human
  • MicroRNAs
  • Mta1 protein, human
  • RNA, Long Noncoding
  • Repressor Proteins
  • Trans-Activators
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Adenylyl Cyclases
  • adenylate cyclase 3