LINC00261 elevation inhibits angiogenesis and cell cycle progression of pancreatic cancer cells by upregulating SCP2 via targeting FOXP3

J Cell Mol Med. 2021 Oct;25(20):9826-9836. doi: 10.1111/jcmm.16930. Epub 2021 Sep 19.

Abstract

Long non-coding RNAs (lncRNAs) biological functions and molecular mechanisms associated with pancreatic cancer (PC) remain to be poorly elucidated. We aimed to clarify the role of lncRNA LINC00261 (LINC00261) in PC and confirm its regulatory mechanisms. Bioinformatics analysis, RNA pull-down and RIP assays were performed to investigate relationship between LINC00261 and forkhead box P3 (FOXP3). Further, dual-luciferase reporter gene and ChIP assays were employed to confirm the relationship among LINC00261, FOXP3 and sterol carrier protein-2 (SCP2). PC cells were introduced with a series of vectors to verify the effects of LINC00261 and SCP2 on the viability, cell cycle progression, migration and angiogenesis of PC cells. Nude mice with the xenograft tumour were used to evaluate the effects LINC00261 on the tumourigenicity. LINC00261 was lowly expressed in PC tissues and cells. SCP2 was inhibited by LINC00261 through FOXP3. Functionally, upregulated LINC00261 or downregulated SCP2 led to reduced cell viability, migration, angiogenesis and tumourigenicity potentials. This study demonstrated the inhibitory role of LINC00261 in the angiogenesis and cell cycle progression of PC cells. It acts through the negative regulation of SCP2 via targeting FOXP3. Findings in this study highlight a potentially biomarker for PC treatment.

Keywords: angiogenesis; cell cycle progression; forkhead box P3; long non-coding RNA LINC00261; pancreatic cancer; sterol carrier protein-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Computational Biology / methods
  • Disease Models, Animal
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Mice
  • Neovascularization, Pathologic / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • RNA Interference
  • RNA, Long Noncoding / genetics*

Substances

  • Carrier Proteins
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • RNA, Long Noncoding
  • long non-coding RNA 00261, human
  • sterol carrier proteins