LncRNA CACS15 contributes to oxaliplatin resistance in colorectal cancer by positively regulating ABCC1 through sponging miR-145

Arch Biochem Biophys. 2019 Mar 15:663:183-191. doi: 10.1016/j.abb.2019.01.005. Epub 2019 Jan 9.

Abstract

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are implicated with chemoresistance of cancers. However, their functional role and molecular mechanisms in colorectal cancer (CRC) chemoresistance are still largely unclear. In this work, we aimed to investigate the functional role of lncRNA cancer susceptibility candidate 15 (CASC15) in oxaliplatin (OXA) resistance of CRC and reveal the underlying molecular mechanism. Our results discovered that CASC15 was up-regulated in OXA-resistant CRC tissues and cells. Patients with high CASC15 expression level had a poor prognosis. CASC15 knockdown re-sensitized HT29/OXA and HCT116/OXA cells to OXA. Moreover, CASC15 could act as a competing endogenous RNA (ceRNA) to de-repress ABCC1 expression through sponging miR-145. miR-145 overexpression or ABCC1 knockdown could mimic the functional role of down-regulated CACS15 in OXA resistance, which was counteracted by CASC15 overexpression. Furthermore, CASC15 knockdown facilitated OXA sensitivity of OXA-resistant CRC cells in vivo. In summary, CASC15 silencing overcame OXA resistance of CRC by regulating miR-145/ABCC1 axis, providing a potential therapeutic target for CRC chemoresistance.

Keywords: ABCC1; Colorectal cancer; Oxaliplatin; lncRNA CASC15; miR-145.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Knockdown Techniques
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Oxaliplatin / pharmacology*
  • Oxaliplatin / therapeutic use
  • Prognosis
  • RNA, Long Noncoding / physiology*

Substances

  • Antineoplastic Agents
  • MIRN145 microRNA, human
  • MicroRNAs
  • Multidrug Resistance-Associated Proteins
  • RNA, Long Noncoding
  • Oxaliplatin
  • multidrug resistance-associated protein 1