Abstract
Abstract Background: The recent discovery of the long noncoding RNA genes has dramatically altered our understanding of cancer genetics. Breast cancer is a collection of diseases with variable molecular underpinnings that modulate therapeutic responses, disease free intervals, and long-term survival of patients. In this study, we report the identification of a lncRNA signature associated with metastasis of breast cancer. Methods: LINC00926 was identified by microarray and validated by real-time PCR. Survival analysis was evaluated using the Kaplan-Meier method and assessed using the log-rank test. In vitro assays were preformed to explore the biological effects of LINC00926 in BC cells. The interaction of LINC00926 with HNRNPC was identified by RNA pull-down and RNA immunoprecipitation. Results: We assessed the expression of LINC00926 in 293 invasive breast cancer tumors in Fudan University Shanghai Cancer Center (FUSCC), Kaplan-Meier analysis revealed that the high expression level of LINC00926 was significantly associated with good overall survival (OS) (P = 0.009) and disease-free survival (DFS) (P = 0.007). Low expression of LINC00926 was also associated with poor overall survival in TCGA database. Cox proportional hazards regression analysis further demonstrated that high LINC00926 expression level was an independent prognostic factor for overall survival (HR: 0.37; 95% CI: 0.16-0.84; P = 0.018) and DFS (HR: 0.48; 95% CI: 0.24-0.98; P = 0.045). These results suggested that LINC00926 might be a potential tumor-suppressor lncRNA in breast cancer. LINC00926 was mainly located in the cell nucleus. Overexpression of full-length LINC00926 significantly inhibited breast cancer proliferation, invasion and migration in vitro. Knockdown transcriptional activation of LINC00926 promotes the ability of tumor proliferation and metastasis. Via RNA pull-down assay and mass spectrometry, HNRNPC was found to interact with LINC00926. HNRNPC repression is well known to induce alternative splicing. Therefore, such compensating machinery may monitor the RNA post-transcriptional processing and block dsRNA generation. This hypothesis certainly worths further investigation. Conclusion: Our study revealed a correlation between LINC00926 and metastases in breast cancer. High level of LINC00926 was associated with better metastasis-free survival. The changed metastasis phenotype may be mediated by the interaction of LINC00926 and HNRNPC via meditation of post-transcriptional processing in breast cancer cells. Therefore, LINC00926 may represent a potential predictive biomarker for inhibiting breast cancer invasion-metastasis cascade. Citation Format: Jianjing Hou, Bingqiu Xiu, Weiru Ji, Qi Zhang, Rong Guo, Yayun Chi, Jiong Wu. LINC00926 interacts with HNRNPC and suppress metastasis in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-08.
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