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

Abstract

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
• tamoxifen
• miR-363
• SERTAD3
• ceRNA
• TGF-β/Smad pathway

Disclosure statement

The authors declared that they have no competing interests.

Additional information

Funding

The work was supported by the Henan Medical Science and Technology Research Project (201602140). Study Abroad Program of Henan Province (grant number 2017047).