Long non-coding RNA LOC389641 promotes progression of pancreatic ductal adenocarcinoma and increases cell invasion by regulating E-cadherin in a TNFRSF10A-related manner

Cancer Lett. 2016 Feb 28;371(2):354-65. doi: 10.1016/j.canlet.2015.12.010. Epub 2015 Dec 18.

Abstract

Long non-coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in pancreatic ductal adenocarcinoma (PDAC) are poorly understood. Here, we found that a novel lncRNA, LOC389641, was upregulated in PDAC tissues and cell lines. The expression of LOC389641 was significantly correlated with staging, lymph node metastasis and overall survival. Knockdown of LOC389641 impaired cell proliferation and invasion and induced cell apoptosis in vitro, whereas overexpression of LOC389641 had the opposite effect. The growth promoting effect of LOC389641 was also demonstrated in vivo. Further, a significant negative correlation was observed between E-cadherin levels and LOC389641 levels in vivo. Knockdown of LOC389641 upregulated E-cadherin expression, but knockdown of E-cadherin had a limited influence on LOC389641. Importantly, after E-cadherin was inhibited, the enhancement of LOC389641 on cell invasion was hindered. Moreover, the expression of LOC389641 was closely associated with its genomic neighboring gene TNFRSF10A. Lastly, knockdown experiments showed that TNFRSF10A might be a connection between LOC389641and E-cadherin. We conclude that LOC389641 promotes PDAC progression and increases cell invasion by regulating E-cadherin with the possible involvement of TNFRSF10A.

Keywords: E-cadherin; Invasion; LncRNAs; Pancreatic ductal adenocarcinoma; TNFRSF10A.

MeSH terms

  • Animals
  • Antigens, CD
  • Apoptosis
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Proportional Hazards Models
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Signal Transduction
  • Time Factors
  • Transfection

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • LOC389641 long non-coding RNA, human
  • RNA, Long Noncoding
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10A protein, human