Upregulation of long non-coding RNA LINC00963 has been observed in several cancer types. In this study, we analyzed the clinical and biological significance of LINC00963 in breast cancer. The key microRNA (miR) mediating the action of LINC00963 was identified. We show that LINC00963 upregulation is correlated with aggressive parameters of breast cancer. Silencing of LINC00963 suppresses the proliferation and tumorigenesis of breast cancer cells, whereas LINC00963 overexpression exerts an opposite effect. Knockdown of LINC00963 enhances DNA damage and oxidative stress and sensitizes breast cancer cells to radiation. Mechanistically, LINC00963 antagonizes the repressive activity of miR-324-3p on ACK1 expression. Clinically, there is a negative correlation between miR-324-3p and LINC00963 expression in breast cancer tissues. Overexpression of LINC00963 or ACK1 rescues the inhibitory effects of miR-324-3p on breast cancer cell proliferation and radiosensitivity. In addition, knockdown of ACK1 attenuates LINC00963-dependent breast cancer growth and tumorigenesis. Taken together, LINC00963 promotes tumorigenesis and radioresistance in breast cancer through interplay with miR-324-3p and derepression of ACK1. LINC00963 may represent a potential target for the treatment of breast cancer.
Background. The impact of postmastectomy radiotherapy (PMRT) in patients receiving neoadjuvant chemotherapy (NAC) is unclear. The purpose of this study is to identify the patients who may benefit from PMRT. Methods. We retrospectively analysed patients with clinical stage II-III breast cancer who underwent NAC and modified radical mastectomy at our centre from 2007 to 2015. We investigated the relationship amongst locoregional recurrence rate (LRR), disease-free survival (DFS), and clinical pathological characters. Results. A total of 554 patients were analysed in this study. The median follow-up time was 65 months. Amongst the patients, 58 (10.5%) had locoregional recurrence, 138 (24.9%) had distant metastasis, and 72 (13.0%) patients died. The 5-year cumulative incidence of LRR and DFS was 9.2% and 74.2%, respectively. A total of 399 (72%) patients received PMRT and 155 (28%) did not. The 5-year LRR of the patients with PMRT (7.3% vs. 14.1%,
P
=
0.01
) decreased significantly. We found that PMRT was an independent prognostic factor of LRR and DFS. Patients with the persistent involvement of 1–3 lymph nodes (ypN1) and more than 4 positive lymph nodes (ypN2-3) had a better outcome after PMRT than those without. However, the LRR and DFS of patients with negative lymph nodes at the time of surgery (ypN0) and who received PMRT showed no significant benefits. Amongst all patients with the three molecular subtypes of breast cancer, patients with triple-negative breast cancer had the highest pathological complete response rate but the worst prognosis (
P
=
0.001
). Conclusion. Results showed that PMRT significantly reduced the LRR of patients with clinical stage II-III breast cancer after receiving NAC and mastectomy. YpN0 patients derived no local control or survival benefit after receiving PMRT, whereas those with ypN1 and ypN2-3 could obviously benefit from PMRT.
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