Abstract
BackgroundLong noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. However, the functional roles of lncRNAs in breast cancer remain largely unknown.MethodsBased on public databases and integrating bioinformatics analyses, the overexpression of lncRNA BCRT1 in breast cancer tissues was detected and further validated in a cohort of breast cancer tissues. The effects of lncRNA BCRT1 on proliferation, migration, invasion and macrophage polarization were determined by in vitro and in vivo experiments. Luciferase reporter assay and RNA immunoprecipitation (RIP) were carried out to reveal the interaction between lncRNA BCRT1, miR-1303, and PTBP3. Chromatin immunoprecipitation (ChIP) and RT-PCR were used to evaluate the regulatory effect of hypoxia-inducible factor-1α (HIF-1α) on lncRNA BCRT1.ResultsLncRNA BCRT1 was significantly upregulated in breast cancer tissues, which was correlated with poor prognosis in breast cancer patients. LncRNA BCRT1 knockdown remarkably suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, lncRNA BCRT1 could competitively bind with miR-1303 to prevent the degradation of its target gene PTBP3, which acts as a tumor-promoter in breast cancer. LncRNA BCRT1 overexpression could promote M2 polarization of macrophages, mediated by exosomes, which further accelerated breast cancer progression. Furthermore, lncRNA BCRT1 was upregulated in response to hypoxia, which was attributed to the binding of HIF-1α to HREs in the lncRNA BCRT1 promoter.ConclusionsCollectively, these results reveal a novel HIF-1α/lncRNA BCRT1/miR-1303/PTBP3 pathway for breast cancer progression and suggest that lncRNA BCRT1 might be a potential biomarker and therapeutic target for breast cancer.
Highlights
Long noncoding RNAs play crucial roles in tumor progression and are aberrantly expressed in various cancers
Long non-coding RNAs (LncRNAs) BCRT1 expression is upregulated in breast cancer and associated with poor prognosis To identify important Long noncoding RNAs (lncRNAs) that potentially participate in breast cancer progression, we analyzed the lncRNA expression profiles using public databases (GSE112848 and a The Cancer Genome Atlas (TCGA) dataset) (Fig. 1a-b)
Using the Open Reading Frame (ORF) Finder and conserved domain database, we found that lncRNA BCRT1 had little potential to code proteins, which was in accordance with the results of five different online metrics (Additional file 3: Figure S1d-f)
Summary
Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are aberrantly expressed in various cancers. The functional roles of lncRNAs in breast cancer remain largely unknown. Despite advances in diagnosis and combined treatments, the prognosis of breast cancer patients remains unsatisfactory [1, 2]. A more comprehensive understanding of the mechanism of progression and metastasis is important for improving the prognosis of breast cancer patients. Despite the lack of cross-species conservation [8], researchers in our laboratory and others have demonstrated that lncRNAs are frequently dysregulated in cancers and are involved in the progression and metastasis of multiple malignancies [9, 10]. The clinical significance and biological mechanisms of the vast majority of lncRNAs in the regulation of breast cancer remain largely unknown
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.
