Functional role of a long non-coding RNA LIFR-AS1/miR-29a/TNFAIP3 axis in colorectal cancer resistance to pohotodynamic therapy

Biochim Biophys Acta Mol Basis Dis. 2018 Sep;1864(9 Pt B):2871-2880. doi: 10.1016/j.bbadis.2018.05.020. Epub 2018 May 25.


Colorectal Cancer (CRC) is one of the most common digestive system malignant tumors. Recently, PDT has been used as a first-line treatment for colon cancer; however, limited curative effect was obtained due to resistance of CRC to PDT. During the past decades, accumulating CRC-related long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs have been reported to exert diverse functions through various biological processes; their dysregulation might trigger and/or promote the pathological changes. Herein, we performed microarrays analysis to identify dysregulated lncRNAs, miRNAs and mRNAs in PDT-treated HCT116 cells to figure out the lncRNA-miRNA interactions related to the resistance of CRC to PDT treatment, and the downstream mRNA target, as well as the molecular mechanism. We found a total of 1096 lncRNAs dysregulated in PDT-treated CRC HCT116 cells; among them, LIFR-AS1 negatively interacted with miR-29a, one of the dysregulated miRNAs in PDT-treated CRC cells, to affect the resistance of CRC to PDT. LIFR-AS1 knockdown attenuated, whereas miR-29a inhibition enhanced the cellular effect of PDT on HCT116 cell proliferation and apoptosis. Furthermore, among the dysregulated mRNAs, TNFAIP3 was confirmed to be a direct target of miR-29a and exerted a similar effect to LIFR-AS1 on the cellular effects of PDT. In summary, LIFR-AS1 serves as a competitive endogenous RNA (ceRNA) for miR-29a to inhibit its expression and up-regulate downstream target TNFAIP3 expression, finally modulating the resistance of CRC to PDT. We provide an experimental basis for this lncRNA/miRNA/mRNA network being a promising target in CRC resistance to PDT treatment.

Keywords: Colorectal cancer (CRC), photodynamic therapy (PDT); Long non-coding RNA (lncRNA) LIFR-AS1; Microarrays analysis; TNFAIP3; miR-29a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Computational Biology
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks / genetics
  • Glucosides / administration & dosage
  • HCT116 Cells
  • Humans
  • Leukemia Inhibitory Factor Receptor alpha Subunit / genetics
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Photochemotherapy
  • Porphyrins / administration & dosage
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics*
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism
  • Up-Regulation


  • 5,10,15,20-tetrakis(4-(glucopyranosylthio-2,3,5,6-tetrafluorophenyl)-2,3-(methano(N-methyl)iminomethano)chlorin
  • 5,10,15,20-tetrakis(pentafluorophenyl)-2,3-(methano(N-methyl)iminomethano))chlorin
  • Glucosides
  • LIFR protein, human
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • MIRN29a microRNA, human
  • MicroRNAs
  • Porphyrins
  • RNA, Long Noncoding
  • RNA, Messenger
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3