LncRNA LINP1 promotes malignant progression of pancreatic cancer by adsorbing microRNA-491-3p

Eur Rev Med Pharmacol Sci. 2020 Sep;24(18):9315-9324. doi: 10.26355/eurrev_202009_23013.

Abstract

Objective: The purpose of this study was to explore the mechanism by which long noncoding RNA (lncRNA) LINP1 promoted the development of pancreatic cancer (PCa). Meanwhile, the regulatory relationship between lncRNA LINP1 and microRNA-491-3p was further investigated to provide an effective theoretical basis for the treatment of this cancer.

Patients and methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was carried out to examine lncRNA LINP1 and microRNA-491-3p expression in tumor tissue specimens collected from 56 PCa patients, and the interplay between lncRNA LINP1 expression and some clinical indicators, as well as prognosis of patients with PCa was also analyzed. Meanwhile, in vitro, qRT-PCR further verified lncRNA LINP1 level in PCa cell lines. In addition, lncRNA LINP1 knockdown model was constructed using lentivirus in PCa cell lines CFPAC-1 and BxPC-3, and Cell Counting Kit-8 (CCK-8), transwell, and cell wound healing assays were carried out to evaluate the impact of lncRNA LINP1 on the function of PCa cells. Finally, Dual-Luciferase reporting assay and cell reverse experiments were applied to uncover the potential mechanism.

Results: QRT-PCR revealed that lncRNA LINP1 showed a significantly higher expression in pancreatic tumor tissue samples than in adjacent normal ones. Compared with patients with low expression of lncRNA LINP1, patients with highly expressed lncRNA LINP1 showed a higher incidence of distant metastasis, but a lower overall survival rate. In addition, compared to the sh-NC group, the proliferation, invasion, and migration ability of PCa cells decreased remarkably in LINP1 knockdown group. The results of Luciferase reporting assay demonstrated that lncRNA LINP1 could be targeted by microRNA-491-3p through a specific binding site, and qRT-PCR results uncovered a negative correlation between microRNA-491-3p and lncRNA LINP1 expression in PCa tissues. Finally, the recovery experiment revealed a mutual regulation between LINP1 and microRNA-491-3p, which may jointly regulate the malignant progression of PCa.

Conclusions: LncRNA LINP1 is able to enhance the proliferation and metastasis of PCa cells by modulating microRNA-491-3p, thus affecting the incidence of lymph node or distant metastasis and prognosis of patients with PCa.

MeSH terms

  • Adsorption
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • LINP1 non-coding RNA, human
  • MIRN491 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding