Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer

Cell Physiol Biochem. 2018;48(1):194-207. doi: 10.1159/000491718. Epub 2018 Jul 13.

Abstract

Background/aims: An increasing body of evidence shows that long noncoding RNAs (lncRNAs) are involved in many different cancers. In this study, we aimed to investigate the competing endogenous RNA (ceRNA)-dependent mechanism by which the lncRNA GAS5 contributes to the development of breast cancer.

Methods: A total of 68 breast cancer patients were enrolled, and breast cancer and adjacent normal tissues were collected. The human breast cancer cell lines MDA-MB-231, MDA-MB-453, BT549, SK-BR-3 and MCF-7 and human breast cell line MCF10A were utilized in this study. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting were performed to detect expression of relative factors. RNA immunoprecipitation (RIP) was used to evaluate the relationship between GAS5 and miR-23a, and a dual luciferase reporter gene assay was employed to assess the relationship between ATG3 and miR-23a. A subcutaneous xenograft nude mouse model was generated to examine the role of GAS5 and its regulatory pathway in autophagy.

Results: GAS5 levels were frequently decreased in breast cancer tissues and cell lines, and its relatively low expression was closely related to a larger tumour size, advanced tumour-node-metastasis (TNM) stage and estrogen receptor-negative (ER-) breast cancer tissues. More importantly, we found that GAS5 promoted autophagy, with enhanced autophagosome formation after GAS5 overexpression. GAS5 was found to act as a microRNA sponge in a pathway that included miR-23a and its target gene ATG3. The GAS5-miR-23a-ATG3 axis significantly regulated autophagy in vivo and in vitro.

Conclusions: In summary, we report that the GAS5-miR-23a-ATG3 axis can be regarded as a key regulator of autophagy pathways in breast cancer; it may constitute a promising biomarker and therapeutic target in the future.

Keywords: ATG3; Autophagy; Breast cancer; CeRNA; Gas5; MiR-23a.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Antagomirs / metabolism
  • Antagomirs / pharmacology
  • Autophagy
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lymphatic Metastasis
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Neoplasm Staging
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / pharmacology
  • Sequestosome-1 Protein / metabolism
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*

Substances

  • Antagomirs
  • Autophagy-Related Proteins
  • GAS5 long non-coding RNA, human
  • MIRN23a microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Sequestosome-1 Protein
  • Ubiquitin-Conjugating Enzymes
  • ATG3 protein, human