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19 June 2019 : Clinical Research  

Long Non-Coding RNA Differentiation Antagonizing Nonprotein Coding RNA (DANCR) Promotes Proliferation and Invasion of Pancreatic Cancer by Sponging miR-214-5p to Regulate E2F2 Expression

Zhichao Yao1ACE, Qiyu Chen2BCD, Zhonglin Ni1BCD, Lei Zhou1EFG, Yigeng Wang1CD, Yuetao Yang1AF, He Huang1ABEG*

DOI: 10.12659/MSM.916960

Med Sci Monit 2019; 25:4544-4552

Abstract

BACKGROUND: Long non-coding RNA differentiation antagonizing nonprotein coding RNA (lncRNA DANCR) has been reported to act as an oncogene in various human cancers. The role of DANCR in development of pancreatic cancer (PC) is unknown. The aim of our research was to investigate the biological role of DANCR in PC.

MATERIAL AND METHODS: Expressions of DANCR, miR-214-5p, and E2F2 mRNA in PC tissues and cell lines were examined by qRT-PCR. Western blotting was carried out for detection of E2F2 protein expression in PC cells. Transwell assays were used to examine the metastatic ability of PC cells, while CCK-8 and colony formation assay were applied to evaluate cell proliferation. The effects of DANCR on PC cells were assessed by knockdown in vitro and in vivo. The regulatory mechanism of competitive endogenous RNAs were obtained from bioinformatics prediction and luciferase reporter assay.

RESULTS: DANCR was markedly upregulated in clinical tissues and cell lines of PC. High DANCR expression exhibited a significant correlation with poor prognosis. DANCR knockdown inhibited growth and metastasis of PC cells. Furthermore, DANCR acted as sponge to regulate miR-214-5p, and miR-214-5p inhibitor reversed the effects of DANCR knockdown on PC cells. Moreover, DANCR positively modulated E2F2 expression through miR-214-5p in PC cells.

CONCLUSIONS: Collectively, our findings demonstrated that lncRNA DANCR/miR-214-5p/E2F2 axis acts as an oncogene in PC development, which might provide a potential target for PC therapy.

Keywords: MicroRNAs, Pancreatic Neoplasms, RNA, Long Noncoding, Aged, Aged, 80 and over, Apoptosis, Cell Differentiation, E2F2 Transcription Factor, HEK293 Cells, Mice, Inbred BALB C, Middle Aged, Neoplasm Invasiveness

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750