GATA1-Activated HNF1A-AS1 Facilitates the Progression of Triple-Negative Breast Cancer via Sponging miR-32-5p to Upregulate RNF38

Abstract

Background

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer with a high mortality rate. Recently, long non-coding RNAs (lncRNAs) are confirmed to modulate the progression of assorted cancers, including TNBC. However, the functions of lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) in TNBC are still unclear.

Aim

We aimed to investigate the function and mechanism of HNF1A-AS1 in TNBC.

Methods

The expression of genes in TNBC cells was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In vitro loss-of-function assays and in vivo xenograft experiments were conducted for evaluating the impact of HNF1A-AS1 on TNBC progression. RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays were utilized for assessing the correlations between molecules.

Results

We discovered that HNF1A-AS1 was highly expressed in TNBC tissues and cells. Knockdown of HNF1A-AS1 restrained cell proliferation but accelerated cell apoptosis. Besides, GATA-binding protein 1 (GATA1) activated HNF1A-AS1 transcription in TNBC. MicroRNA-32-5p (miR-32-5p) was slowly expressed in TNBC cells and sponged by HNF1A-AS1, and its overexpression hinders TNBC cell growth. Ring finger protein 38 (RNF38) was verified as the target of miR-32-5p, and HNF1A-AS1 was a competing endogenous RNA (ceRNA) of RNF38 through sponging miR-32-5p. Rescue experiments indicated that upregulation of RNF38 reversed the inhibited impacts of silencing HNF1A-AS1 on TNBC cell growth.

Conclusion

GATA1-activated HNF1A-AS1 facilitated TNBC progression via miR-32-5p/RNF38 axis. The findings may provide new roads for developing targeted therapies of TNBC.

Keywords:

• HNF1A-AS1
• miR-32-5p
• RNF38
• triple-negative breast cancer

Acknowledgment

We thank all the participators.

Data Sharing Statement

Data have all been provided in the manuscript and supplementary materials.

Ethics Approval and Informed Consent

This work was carried out with the approval of the Ethics Committee of the First People’s Hospital of Yunnan Province. All involvers signed the informed consents before surgery.

Consent for Publication

All involvers signed the informed consents before surgery.

Disclosure

No conflicts of financial interest are enclosed in this study.