The high expression of long non-coding RNA PANDAR indicates a poor prognosis for colorectal cancer and promotes metastasis by EMT pathway

J Cancer Res Clin Oncol. 2017 Jan;143(1):71-81. doi: 10.1007/s00432-016-2252-y. Epub 2016 Sep 14.

Abstract

Background: Long non-coding RNAs (lncRNAs) have been shown to have crucial regulatory roles in human cancer biology. LncRNA PANDAR is a novel identified lncRNA that was previously reported to be increased in various cancers; however, its effect in colorectal cancer (CRC) remains unknown. The aim of this study was to explore the expression and role of lncRNA PANDAR in CRC.

Methods: The expression of lncRNA PANDAR was examined in CRC samples and cell lines by qRT-PCR. Kaplan-Meier survival analysis and univariate and multivariate Cox proportional hazards model were performed to evaluate the clinical and prognostic significance of lncRNA PANDAR in CRC patients. Furthermore, the biological function of lncRNA PANDAR on tumor cell growth, apoptosis and mobility was investigated through CCK-8, soft agar colony formation, flow cytometry, transwell migration and invasion assays in vitro. The potential mechanism of lncRNA PANDAR was demonstrated by Western blot and qRT-PCR.

Results: The expression level of PANDAR was higher in CRC tissues and cells compared to adjacent non-tumor tissues and normal colonic epithelial cells. Patients with high PANDAR expression level had poorer overall survival than those with low PANDAR expression. Moreover, multivariate analysis showed that the status of PANDAR expression was an independent prognostic indicator for CRC. Knockdown of PANDAR could inhibit cell growth, migration and invasion, arrest cell cycle as well as induce apoptosis of CRC cells in vitro study. In addition, PANDAR could affect epithelial-mesenchymal transition through inhibiting N-cadherin, vimentin, β-catenin, Snail and Twist expression and increasing the expression levels of E-cadherin.

Conclusion: Our data suggested that lncRNA PANDAR was a novel molecule involved in CRC progression, which provided a potential prognostic biomarker and therapeutic target for new therapies in patients with CRC.

Keywords: Colorectal cancer; Long non-coding RNA; PANDAR; Prognosis.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • RNA, Long Noncoding
  • long non-coding RNA PANDAR, human