Long noncoding RNA BLACAT1 modulates ABCB1 to promote oxaliplatin resistance of gastric cancer via sponging miR-361

Biomed Pharmacother. 2018 Mar;99:832-838. doi: 10.1016/j.biopha.2018.01.130. Epub 2018 Feb 20.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as novel gene regulators in multiple tumorigenesis and chemoresistance. However, their potential roles and molecular mechanisms in gastric cancer chemoresistance remain unclear. In present study, our team investigated the role and potential regulatory mechanism of lncRNA s bladder cancer associated transcript-1 (BLACAT1) in the gastric cancer chemoresistance. Results showed that BLACAT1 expression was up-regulated in the oxaliplatin (OXA) resistant gastric cancer tissue and cells compared with OXA-sensitive tissue and parental cell lines. In vitro, BLACAT1 knockdown decreased the expression levels of drug resistance related genes and ABCB1 protein. Besides, BLACAT1 knockdown significantly promoted apoptosis and down-regulated the invasion and the IC50 value of oxaliplatin. In vivo, BLACAT1 knockdown suppressed the tumor growth of gastric cancer cells. Bioinformatics tools and luciferase assay indicated that miR-361 both targeted 3?-UTR of BLACAT1 and ABCB1mRNA, suggesting the BLACAT1/miR-361/ABCB1 regulatory pathway. In summary, our results conclude that BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361, providing a novel insight for the chemoresistance of gastric cancer.

Keywords: ABCB1; BLACAT1; Gastric cancer; Long non-coding RNA; Oxaliplatin resistance; miR-361.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Humans
  • Inhibitory Concentration 50
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Organoplatinum Compounds / pharmacology*
  • Oxaliplatin
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents
  • MIRN361 microRNA, human
  • MicroRNAs
  • Organoplatinum Compounds
  • RNA, Long Noncoding
  • long noncoding RNA BLACAT1, human
  • Oxaliplatin