Upregulated long non-coding RNA SPRY4-IT1 predicts dismal prognosis for pancreatic ductal adenocarcinoma and regulates cell proliferation and apoptosis

Gene. 2018 Jun 15:659:52-58. doi: 10.1016/j.gene.2018.03.048. Epub 2018 Mar 15.

Abstract

Recently, long noncoding RNAs (lncRNAs) have been emerged as pivotal regulators in various human cancers, including pancreatic ductal adenocarcinoma (PDAC). SPRY4-intronic transcript 1 (SPRY4-IT1) was reported to be upregulated in some kind of human cancers. Here, we elucidated the biological functions and possible clinical values of SPRY4-IT1 on PDAC. In present study, expression of SPRY4-IT1 in PDAC tissues and corresponding normal tissues were explored by qRT-PCR experiments. The link between SPRY4-IT1 expression levels and clinicopathological significance was further analyzed. In addition, the oncogenic role of SPRY4-IT1 was detected both in vitro and in vivo. The results demonstrated that SPRY4-IT1 was abnormally upregulated in PDAC tissues and cell lines. Tumor stage and differentiation grade was closely correlated with SPRY4-IT1 expression. Additionally, decreased SPRY4-IT1 contributed to tumor suppressive effect through attenuating cell growth, clonogenic ability and facilitating apoptosis via Bcl-2/caspase-3 pathway in PANC1 and Capan-2 cells. Furthermore, the xenograft study confirmed the tumor proliferation-promoting role of SPRY4-IT1 in PANC1 cells. Taken together, these findings indicated that SPRY4-IT1 is a potential therapeutic target and prognosis biomarker for the patients with PDAC.

Keywords: Apoptosis; Long non-coding RNA; Pancreatic ductal adenocarcinoma; Prognosis; SPRY4-IT1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Up-Regulation*

Substances

  • Apoptosis Regulatory Proteins
  • RNA, Long Noncoding
  • long noncoding RNA SPRY4-IT1, human