Long noncoding RNA LINC01559 promotes pancreatic cancer progression by acting as a competing endogenous RNA of miR-1343-3p to upregulate RAF1 expression

Aging (Albany NY). 2020 Jul 17;12(14):14452-14466. doi: 10.18632/aging.103487. Epub 2020 Jul 17.

Abstract

Background: An increasing number of studies have shown that lncRNAs are involved in the biological processes of pancreatic cancer (PC). Hence, we investigated the role of a novel noncoding RNA, LINC01559, involved in PC progression.

Results: LINC01559 and RAF1 were highly expressed in PC, while miR-1343-3p had low expression. High expression of LINC01559 was significantly associated with large tumors, lymph node metastasis, and poor prognosis. Functional experiment results revealed that silencing of LINC01559 significantly suppressed PC cell proliferation and metastasis. Meanwhile, LINC01559 could act as a ceRNA to competitively sponge miR-1343-3p to up-regulate RAF1 and activate its downstream ERK pathwayConclusions: LINC01559 functions as an oncogene in PC progression through acting as a ceRNA of miR-1343-3p. Hence, LINC01559 is a potential diagnostic and therapeutic target.

Methods: RT-qPCR was performed to determine the expression of LINC01559 and miR-1343-3p in PC. Individual patient data were collected to investigate the correlation between clinicopathological features and LINC01559 expression. Subsequently, the expression of LINC01559, miR-1343-3p, and RAF1 was altered using transfection of vectors or inhibitors. Gain- and loss-of-function assays and mechanistic assays were applied to verify the effects of LINC01559, miR-1343-3p, and RAF1 on PC cell proliferation and metastasis in vivo and in vitro.

Keywords: LINC01559; RAF1; miR-1343-3p; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Oncogenes / genetics
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • Proto-Oncogene Proteins c-raf / genetics*
  • RNA, Long Noncoding / pharmacology*
  • Up-Regulation / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • MIRN-1343 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-raf
  • Raf1 protein, human