A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer

Abstract

Breast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.

YB-1 as an Oncoprotein: Functions, Regulation, Post-Translational Modifications, and Targeted Therapy

“…LncRNA AC073352.1 binds to and stabilizes YB-1 protein in breast cancer cells. Interestingly, exosomal lncRNA AC073352.1 also promote angiogenesis in HUVECs by binding to YB-1 [ 123 ]. LncRNA AATBC activates the YAP1/Hippo signaling pathway through the AATBC-YB-1-MST1 axis, promoting breast cancer migration and invasion [ 124 ].…”

HLA complex P5 upregulation is correlated with poor prognosis and tumor progression in esophageal squamous cell carcinoma

“…The interaction mode of lncRNA and protein is critical for cancer initiation, development and progression [ 21 ]. For example, AC073352.1 was reported as a binding partner of YBX1, and increased YBX1 protein stability, promoting breast cancer metastasis and angiogenesis [ 22 ]. BGL3 was shown to be a stabilizer of PTEN protein via binding to PTEN and inhibited papillary thyroid carcinoma growth and metastasis [ 23 ].…”

Noncoding RNAs of Extracellular Vesicles in Tumor Angiogenesis: From Biological Functions to Clinical Significance

“…In GC, exosomal X26nt decreases vascular endothelial cadherin (VE-cadherin) expression by directly binding to the 3'UTR of VE-cadherin mRNA, thereby increasing vascular permeability and angiogenesis in HUVECs [116]. Exosomal AC073352.1 secreted by BC cells is internalised by HUVECs and promotes angiogenesis by interacting with YBX1 and stabilizing its protein expression [93]. Exosomal H19 released by cancer stem cells promotes endothelial tube production by upregulating VEGF [97].…”