The Biological Function of TUSC7/miR-1224-3p Axis in Triple-Negative Breast Cancer

Abstract

Background

Triple-negative breast cancers (TNBC), comprising about 20% of breast cancers, have a poor prognosis. Currently, there is no effective target therapy for TNBC. LncRNA TUSC7 has been identified as a tumor suppressor in osteosarcoma and colorectal cancer. In this study, we investigated the clinical significance and the biological function of TUSC7 in breast cancer.

Methods

We retrospectively evaluated the expression level and clinical significance of TUSC7 in 90 paired breast cancer tissues and normal tissues. The proliferation, migration, and invasion assays were performed to investigate the biological function of TUSC7 in breast cancer. Finally, microarray, a luciferase reporter assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the potential underlying mechanism of tumor suppressor role of TUSC7.

Results

Low TUSC7 expression was found to be an independent prognostic factor of poor overall survival (OS) in TNBC patients. Ectopic expression of TUSC7 inhibited tumor cell growth both in vitro and in vivo. TUSC7 overexpression significantly promoted the sensitivity of MDA-MB-468 cells to paclitaxel and carboplatin. In terms of the mechanism, TUSC7 might perform its biological function through binding with miR-1224-3P and regulating its expression level. Besides, genes in cell cycle pathways, such as BUB3 (budding uninhibited by benzimidazoles 3) and TGF-ß (targeting transforming growth factor β) pathways were downregulated, and genes involved in the MAPK (mitogen-activated protein kinase) (TGFBR2, transforming growth factor-beta receptor 2), PI3K-AKT (phosphoinositide 3-kinase- AKT serine/threonine kinase 1) and NF-κB (nuclear factor-kappa B subunit) pathways were upregulated in TUSC7 knockdown MDA-MB-231 cells.

Conclusion

The low TUSC7 expression is an independent prognostic factor of poor OS of TNBC patients. TUSC7 might inhibit breast cancer cell growth and metastasis both in vitro and vivo through binding with miR-1224-3P and regulating MAPK, PI3K/AKT, and NF-κB signaling pathways.

Keywords:

• TUSC7
• long non-coding RNA
• MiR-1224-3P
• triple-negative breast cancer
• prognosis

Abbreviations

ER, estrogen receptor; HER2, human epidermal growth receptor-2; TNBC, triple-negative breast cancer; LncRNAs, long non-coding RNAs; OS, overall survival; HR, hazards ratios; PR, progesterone receptor; CI, confidence interval; TUSC7, tumor suppressor candidate 7.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author Xiao-Jian Ni on reasonable request.

Ethics Approval and Consent to Participate

This study was approved by the institutional review board of Zhongshan Hospital, Fudan University. Every patient provided written informed consent before enrollment.

Disclosure

The authors reported no conflicts of interest for this work.