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Downregulation of circular RNA circ-LDLRAD3 suppresses pancreatic cancer progression through miR-137-3p/PTN axis.

Abstract
Emerging evidence suggests that dysregulation of circular RNAs (circRNAs) closely associated with cancer progression. In this paper, we focus on exploring the functional role of circ-LDLRAD3 in pancreatic cancer. Gene expression was determined using quantitative reverse transcriptase polymerase chain reaction and Western blot. Cell count kit-8 and 5-ethynyl-2'-deoxyuridine assay were applied to evaluate the proliferation of PANC-1 and SW1990 cells. The migration and invasion of PANC-1 and SW1990 cells were assessed using wound healing assay and transwell invasion assay. Luciferase reporter assay was performed for target validation. The results showed that circ-LDLRAD3 was overexpressed in pancreatic cancer tissues and cell lines. Increased expression of circ-LDLRAD3 was indicative of a poor prognosis in patients with pancreatic cancer. Knockdown of circ-LDLRAD3 repressed the growth of pancreatic cancer in vitro and in vivo. miR-137-3p was identified as a direct target of circ-LDLRAD3. More importantly, upregulation of circ-LDLRAD3 could mitigate the inhibitory effect of miR-137-3p on the proliferation, migration and invasion of pancreatic cancer cells. Besides, circ-LDLRAD3 could regulate the expression of pleiotrophin (PTN) through miR-137-3p. Taken together, knockdown of circ-LDLRAD3 repressed the proliferation, migration and invasion of pancreatic cancer cells through miR-137-3p/PTN axis, providing a new mechanism for pancreatic cancer progression.
AuthorsJun Yao, Ce Zhang, Yanfei Chen, Shegan Gao
JournalLife sciences (Life Sci) Vol. 239 Pg. 116871 (Dec 15 2019) ISSN: 1879-0631 [Electronic] Netherlands
PMID31521692 (Publication Type: Journal Article)
CopyrightCopyright © 2019 Elsevier Inc. All rights reserved.
Chemical References
  • Carrier Proteins
  • Cytokines
  • LDLRAD3 protein, human
  • MIRN137 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Receptors, LDL
  • pleiotrophin
  • RNA
Topics
  • Animals
  • Carrier Proteins (metabolism)
  • Cell Line, Tumor
  • Cell Movement (genetics)
  • Cell Proliferation (genetics)
  • Cytokines (metabolism)
  • Disease Progression
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic (genetics)
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs (genetics, metabolism)
  • Neoplasm Invasiveness (genetics)
  • Pancreas (metabolism)
  • Pancreatic Neoplasms (genetics)
  • RNA (metabolism)
  • RNA, Circular (genetics)
  • Receptors, LDL (genetics, metabolism)

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