lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p

ABSTRACT

Long non-coding RNA (lncRNA) prostate cancer-associated transcript 18 (PCAT18) is a potential diagnostic target for adenocarcinoma. However, its role in triple-negative breast cancer (TNBC) remains largely unknown. Based on data from an online database, a significant decline in lncRNA PCAT18 was observed in patients with TNBC subtype compared to a population with normal breast tissue. Patients with TNBC with high PCAT18 levels presented good outcomes. Patients with TNBC with high PCAT18 had a lower rate of lymph node-positive metastasis than those with low PCAT18. PCAT18-upregulation inhibited, while PCAT18-downregulation promoted, migration and expression of matrix metalloproteinases 9/2 (MMP9/MMP2) and uridylyl phosphate adenosine (uPA) in TNBC cells. Activating transcription factor 7 (ATF7) was positively associated with PCAT18, and ATF7-inhibition abrogated the anti-migration effects of PCAT18 on TNBC cells. Mechanistically, miR-103a-3p directly targeted and inhibited ATF7 expression. PCAT18 competitively sponges miR-103a-3p, promoting the expression of ATF7. Exogenous PCAT18 was associated with lower incidence of lung metastasis followed by the upregulation of ATF7, which was prevented by the treatment of miR-103a-3p mimics. Collectively, PCAT18 was expressed at low levels in TNBC, and PCAT18 could sponge miR-103a-3p and promote ATF7 expression, resulting in prevention of TNBC metastasis. Thus, PCAT18 can serve as a predictive factor for patients with metastatic TNBC.

Graphical Abstract

KEYWORDS:

• Triple-negative breast cancer
• metastasis
• LncRNA PCAT18
• activating transcription factor 7
• MiR-103a-3p

Authors’ contributions

WHM and LL conceived the idea and designed the project; ZJF and LDH performed the in vitro experiments and analysed the data based on the online database; DGM performed the Transwell assay; WQM performed the qRT-PCR and WB assay; ZJF and DGM determined the reporter gene experiment. LDH and WQM collected the online data and performed the IHC/HE staining assay. WHM and LL drafted the text; All authors edited and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

All experiments were approved by the Ethics Committee of Meizhou People’s Hospital.

Data availability

All data generated or analyzed during this study are included in this published article and its additional files.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by the Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translation Research of Hakka Population (Grant No.: 2018B030322003), the Science and Technology Program of Meizhou (Grant No.: 2019B0202001), and the Scientific Research Cultivation Project of Meizhou People's Hospital (Grant No.: PY-C2020020 and PY-C2020031).