Linc00514 promotes breast cancer metastasis and M2 polarization of tumor-associated macrophages via Jagged1-mediated notch signaling pathway

Abstract

Background Tumor-associated macrophages (TAMs) and tumor cells are important components of the tumor microenvironment. M2 polarization of TAMs, which is a major actor in breast cancer malignancy and metastasis, can be induced by breast cancer cells. However, the potential mechanisms of the interaction between breast cancer cells and TAMs remain unclear. Methods The candidate breast cancer-associated long non-coding RNAs (lncRNAs) were analyzed using the GEO database. Functional assays, including MTT assay, Transwell assay, and EdU labeling detection, were performed to investigate the oncogenic role of linc00514 in breast cancer progression. The co-culture and ELISA assays were used to assess the role of linc00514 in macrophage recruitment and M2 polarization. RNA immunoprecipitation, RNA pull-down, and luciferase reporter assays were applied to determine the mechanism of linc00514 in breast cancer metastasis. Mouse xenograft models, mouse pulmonary metastatic models, and mouse primary tumor models were used to assess the role of linc00514 in M2 macrophage polarization and breast cancer tumorigenicity. Results Linc00514 was highly expressed in clinical breast cancer tissues and breast cancer cell lines. Overexpression of linc00514 promoted the proliferation and invasion of breast cancer cells and increased xenograft tumor volumes and pulmonary metastatic nodules. Overexpression of linc00514 also increased the percentage of macrophages expressing M2 markers CD206 and CD163. Mechanistically, linc00514 promoted Jagged1 expression in a transcriptional manner by increasing the phosphorylation of a transcription factor STAT3. Subsequently, Jagged1-mediated Notch signaling pathway promoted IL-4 and IL-6 secretions in breast cancer cells and ultimately inducing M2 polarization of macrophages. Conclusion Linc00514 plays an important role in regulating breast cancer tumorigenicity and M2 macrophage polarization via Jagged1-mediated Notch signaling pathway.

High expression of eIF4E is associated with tumor macrophage infiltration and leads to poor prognosis in breast cancer

“…For example, in ER-negative disease, tumors lacking immune infiltration were associated with the poorest prognosis, whereas in ER-positive disease, their prognosis was between high- and low-infiltration tumor patients [ 46 ]. Similarly, in ER-positive disease, both M0 and M2 macrophages were associated with poorer outcome, with a similar pattern in ER-negative disease [ 47 ]. Our results indicate that eIF4E is positively correlated with macrophage infiltration in BRCA.…”

Macrophage-Related SPP1 as a Potential Biomarker for Early Lymph Node Metastasis in Lung Adenocarcinoma

“…It has been well documented that M2 macrophages promote tumor growth and metastasis ( Tao et al, 2020 ). On the other hand, many studies indicated tumor cells stimulate naive M0 macrophages to differentiate into M2 macrophages ( Liu et al, 2021 ).…”

LINC00514 promotes lipogenesis and tumor progression in esophageal squamous cell carcinoma by sponging miR‑378a‑5p to enhance SPHK1 expression

“…in esophageal squamous cell carcinoma by sponging miR-378a-5p to enhance SPHK1 expression that lncRNAs may constitute novel, promising biomarkers and therapeutic targets for patients with ESCC. Long intergenic non-protein coding RNA 514 (LINC00514) is localized at chromosome 16p13.3, and it is 3,221-bp long (17). LINC00514 has been reported to be closely associated with the development and progression of tumors, including osteosarcoma (18), papillary thyroid cancer (19) and neuroendocrine prostate cancer (20).…”

“…Long intergenic non-protein coding RNA 514 (LINC00514) is localized at chromosome 16p13.3, and it is 3,221-bp long ( 17 ). LINC00514 has been reported to be closely associated with the development and progression of tumors, including osteosarcoma ( 18 ), papillary thyroid cancer ( 19 ) and neuroendocrine prostate cancer ( 20 ).…”