Exosomal microRNA-92b Is a Diagnostic Biomarker in Breast Cancer and Targets Survival-Related MTSS1L to Promote Tumorigenesis

外泌体 microRNA-92b 是乳腺癌的诊断生物标志物,靶向生存相关的 MTSS1L 来促进肿瘤发生

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作者:Jung-Yu Kan, Shen-Liang Shih, Sheau-Fang Yang, Pei-Yi Chu, Fang-Ming Chen, Chung-Liang Li, Yi-Chia Wu, Yao-Tsung Yeh, Ming-Feng Hou, Chih-Po Chiang

Abstract

Exosomal microRNAs (miRNAs) are novel, non-invasive biomarkers for facilitating communication and diagnosing cancer. However, only a few studies have investigated their function and role in the clinical diagnosis of breast cancer. To address this gap, we established a stable cell line, MDA-MB-231-CD63-RFP, and recruited 112 female participants for serum collection. We screened 88 exosomal miRNAs identified through microarray analysis of 231-CD63 and literature screening using real-time PCR; only exosomal miR-92b-5p was significantly increased in patients with breast cancer. It had a significant correlation with stage and discriminated patients from the control with an AUC of 0.787. Exosomal miR-92b-5p impacted the migration, adhesion, and spreading ability of normal human mammary epithelial recipient cells through the downregulation of the actin dynamics regulator MTSS1L. In clinical breast cancer tissue, the expression of MTSS1L was significantly inversely correlated with tissue miR-92b-5p, and high expression of MTSS1L was associated with better 10-year overall survival rates in patients undergoing hormone therapy. In summary, our studies demonstrated that exosomal miR-92b-5p might function as a non-invasive body fluid biomarker for breast cancer detection and provide a novel therapeutic strategy in the axis of miR-92b-5p to MTSS1L for controlling metastasis and improving patient survival.

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