Silencing long non-coding RNA HNF1A-AS1 inhibits growth and resistance to TAM of breast cancer cells via the microRNA-363/SERTAD3 axis

J Drug Target. 2021 Aug;29(7):742-753. doi: 10.1080/1061186X.2021.1878362. Epub 2021 May 17.


Long non-coding RNAs (lncRNAs) can exert effects on drug resistance of cancer cells. This study investigated the role of lncRNA HNF1A-antisense 1 (HNF1A-AS1) in growth and Tamoxifen (TAM) sensitivity of breast cancer (BC) cells. HNF1A-AS1 expression was promoted in BC cells and tissues. BC cells with HNF1A-AS1 silencing were constructed to detect cell proliferation. TAM resistant cell line with HNF1A-AS1 silencing and parent cell line with overexpressed HNF1A-AS1 were constructed to measure drug resistance. Silencing HNF1A-AS1 reduced proliferation and TAM resistance of BC cells. The downstream microRNAs (miRs) of HNF1A-AS1 and its targets were figured out and their functions in TAM resistance of BC cells were identified. HNF1A-AS1 sponged miR-363 to promote SERTAD3 expression. Downregulation of miR-363 or upregulation of SERTAD3 stimulated TAM resistance of BC cells. The findings in vitro were reproduced in in vivo experiments. It could be concluded that silencing HNF1A-AS1 inhibited growth and drug resistance to TAM of BC cells through the miR-363/SERTAD3 axis and the inactivation of the TGF-β/Smad pathway.

Keywords: Breast cancer; LncRNA HNF1A-antisense 1; SERTAD3; TGF-β/Smad pathway; ceRNA; miR-363; tamoxifen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Tamoxifen / administration & dosage
  • Tamoxifen / pharmacology*
  • Trans-Activators / genetics*
  • Up-Regulation
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Hormonal
  • MIRN363 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • SERTAD3 protein, human
  • Trans-Activators
  • long non-coding RNA HNF1A-AS1, human
  • Tamoxifen