Cancer Management and Research (Aug 2020)
Long Intergenic Non-Coding RNA LINC00922 Aggravates the Malignant Phenotype of Breast Cancer by Regulating the microRNA-424-5p/BDNF Axis
Abstract
Xin Yue, Zhuo Wang Department of Breast Surgery, The First People’s Hospital of Jingzhou, Jingzhou, Hubei, 434000, People’s Republic of ChinaCorrespondence: Zhuo Wang Department of Breast SurgeryThe First People’s Hospital of Jingzhou, No. 8 Hangkong Road, Shashi District, Jingzhou, Hubei 434000, People’s Republic of ChinaEmail [email protected]: Long intergenic non-coding RNA 922 (LINC00922) plays a critical role in the progression of lung cancer. In this study, we aimed to quantify LINC00922 expression in breast cancer and determine its influence on the malignant behavior of breast cancer cells in vitro and in vivo. We also investigated the mechanism by which LINC00922 affects the progression of breast cancer.Materials and Methods: Reverse transcription-quantitative polymerase chain reaction was performed to quantify LINC00922 expression in breast cancer tissues and cell lines. The cell counting kit-8 assay, flow cytometry, Transwell migration and invasion assays, and tumor model assays were performed to determine the effects of LINC00922 deficiency on breast cancer cell proliferation, apoptosis, migration and invasion in vitro, and tumor growth in vivo, respectively. Furthermore, bioinformatics analysis was performed to predict the potential target microRNA of LINC00922. The prediction was further evaluated using luciferase reporter and RNA immunoprecipitation assays.Results: LINC00922 was clearly overexpressed in breast cancer tissues and cell lines. LINC00922 depletion restricted breast cancer cell proliferation, migration, and invasion but induced cell apoptosis in vitro. Additionally, its knockdown evidently repressed tumor growth of breast cancer cells in vivo. Mechanistically, LINC00922 was demonstrated to serve as a molecular sponge for miR-424-5p in breast cancer cells. Furthermore, brain-derived neurotrophic factor (BDNF) was verified as a direct target of miR-424-5p in breast cancer cells, and BDNF expression was found to be positively regulated by LINC00922 through sponging miR-425-5p. Rescue experiments further revealed that the influences on breast cancer cell proliferation, apoptosis, migration, and invasion induced by LINC00922 silencing were abrogated by increasing the output of the miR-424-5p/BDNF axis.Conclusion: The LINC00922/miR-424-5p/BDNF pathway is implicated in the acceleration of the malignant behavior of breast cancer cells. These findings suggest that this pathway is a promising novel molecular target in breast cancer therapy.Keywords: RNA immunoprecipitation, quantitative reverse transcription PCR, brain-derived neurotrophic factor, apoptosis, molecular sponge
