Knockdown of LINC02465 Suppresses Gastric Cancer Cell Growth and Metastasis Via PI3K/AKT Pathway

Hum Gene Ther Clin Dev. 2019 Mar;30(1):19-28. doi: 10.1089/humc.2018.177. Epub 2019 Feb 7.

Abstract

Gastric cancer (GC) is the second primary cause of cancer-associated mortality around the world. Long noncoding RNAs (lncRNAs) are critical modulators of multiple cellular processes, and their abnormal expression and/or function are related to a variety of diseases, including cancer. Various lncRNAs have been shown to exert a functional role in GC, but more still remain to be identified, since the therapies for GC patients are limited. Here we discover LINC02465, a novel recognized lncRNA, is upregulated and correlated with tumor size, tumor stage, lymph node metastasis, and differentiation in gastric cancer. In addition, we found that high LINC02465 level in GC patients is closely related to poor prognosis. Moreover, our findings reveal that LINC02465 silence suppresses cell proliferation and migration, invasion, and epithelial-mesenchymal transition in vitro. Conversely, LINC02465 overexpression displays a completely opposite way. Meanwhile, LINC02465 inhibition also limits tumor growth in vivo. Mechanistically, LINC02465 inhibition inactivates PI3K/AKT signaling pathway, and the activation of this pathway by 740Y-P reverses the inhibition effect of LINC02465 suppression on biological behaviors of GC cells. Taken together, LINC02465 is an oncogenic lncRNA that facilitates the tumorigenesis and progression of GC via PI3K/AKT pathway, demonstrating a novel effective therapeutic target and prognostic biomarker for GC patients.

Keywords: PI3K/AKT pathway; cell growth; gastric cancer; metastasis.

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Genetic Therapy*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Metastasis
  • Phosphatidylinositol 3-Kinases / genetics
  • Prognosis*
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / therapeutic use*
  • Signal Transduction / genetics
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*

Substances

  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt