Background: Triple negative breast cancer (TNBC) poses a great threat to patient prognosis. LncRNA-miRNA is a molecular module formed by a long non-coding RNA (LncRNA) and a microRNA (miRNA) that mediates the metastatic potential of tumours such as TNBC, and luteolin (LU) is a natural compound with anti-TNBC activity.
Objective: We aim to explore the regulatory mechanism of terminal differentiation-induced non-coding RNA (TINCR)-miR-761 molecular module in early TNBC, as well as its influence on anti-tumor activity of LU.
Methods: The serum was collected from TNBC patients in early stage to detect the expression of TINCR and miR-761 using RT-PCR. Transwell method was applied for the determination of cell migration and invasion, Western blot for epithelial–mesenchymal transition (EMT), flow cytometry (FCM) for cell apoptosis, and dual luciferase reporter and RNA pull-down experiment for the verification of the targeted relationship between TINCR and miR-761.
Results: Both TINCR and miR-761 were up-regulated in the serum of patients with early TNBC and the area under the curve (AUC) of the two for distinguishing TNBC from BC was not less than 0.850. In the cell function tests, down-regulation of TINCR or miR-761 notably suppressed the metastatic potentials (cell migration, invasion and EMT) of TNBC cells were remarkably inhibited, while up-regulation of TINCR or miR-761 notably promoted the metastatic potentials. We also confirmed that TINCR acts as the molecular sponge of miR-761, and has positive regulation on it. Besides, LU can significantly down-regulate TINCR and miR-761, and partially offset the anti-TNBC activity of LU when they were abnormally up-regulated, which was mainly reflected in the decrease of anti-proliferation and pro-apoptotic ability of LU against TNBC.
Conclusion: There is an imbalance of TINCR-miR-761 molecular module in early TNBC, which may be a potential new therapeutic target of TNBC.
Keywords: triple negative breast cancer, TINCR, miR-761, metastasis, luteolin