Abstract
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Dysregulation of long non-coding RNAs (lncRNAs) plays crucial roles in the initiation and progression of TNBC. In this study, we analyzed public GEO profiles to verify the key lncRNAs in TNBC. Linc00921 was selected for further study. Low expression of linc00921 was observed in 49 of 95 TNBC tissues. Low expression of linc00921 was correlated with poor postoperative disease-free survival (DFS) and overall survival (OS) of TNBC patients. Overexpression of linc00921 with lentivirus suppressed the proliferation, migration and invasion of TNBC cells. A luciferase reporter assay showed that linc00921 could sponge miR-9-5p in TNBC. Moreover, linc00921 and miR-9-5p occupied the same Argonaute-2 (Ago2) protein in TNBC cells. Leucine zipper tumor suppressor 2 (LZTS2) was recognized as a target gene of miR-9-5p, and thereby a linc00921/miR-9-5p/LZTS2 axis was identified in TNBC cells. Overexpression of linc00921 promoted nuclear export of β-catenin, neutralized its function, and subsequently promoted epithelial-to-mesenchymal transition (EMT) in TNBC. A xenograft tumor mouse model showed that the miR-9-5p inhibitor upregulates LZTS2 expression and induce nuclear export of β-catenin in TNBC. Thus, linc00921 upregulates LZTS2 by sponging miR-9-5p to suppress tumorigenesis and EMT of TNBC. Linc00921/miR-9-5p/LZTS2 axis may be a novel biomarker and therapeutic target for TNBC patients.
Highlights
Breast cancer ranks first in female malignant tumor, threatening women’s health worldwide [1]
Revealing the roles of the tumor-suppressing long non-coding RNAs (lncRNAs) might be conducive to establishing novel treatment strategies for improving the prognosis of triple-negative breast cancer (TNBC)
We analyzed the public Gene Expression Omnibus (GEO) profiles GSE119233 and GSE115275 to verify the key lncRNAs correlated with TNBC
Summary
Breast cancer ranks first in female malignant tumor, threatening women’s health worldwide [1]. (human epidermal growth factor receptor 2) overexpression and triple-negative ( known as basal-like), according to the expression of estrogen receptor (ER), progesterone receptor (PR), Ki-67 and HER-2. Among these 4 subtypes, triple-negative breast cancer (TNBC) still has the poorest prognosis due to its formidable aggressiveness and high rate of recurrence [2]. Despite the improvement in treating approaches including surgery, chemotherapy, radiotherapy and immunotherapy, the overall survival of TNBC patients remains unsatisfactory. Further elucidation of the mechanisms of aberrant expression of tumor suppressor genes is necessary for establishing novel treatment strategies to improve the prognosis of TNBC patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
