Li Li

Objective. Studies revealed an important role of microRNAs (miRNAs) in multiple cancers, including breast cancer. In the present study, we evaluated the role and function of miR-641 in breast cancer. Methods. The expression level of miR-641 in breast cancer cell lines (Hs-578T, MCF7, HCC1937, and MAD-MB-231) was determined by real-time PCR. Functional analyses, including CCK-8 assay, transwell assay, wound-healing assay, and apoptosis detection, were carried out to explore the roles of miRNA-641 in malignant behaviors of breast cancer. Luciferase report assay was used to investigate the regulatory association of miRNA-641 with its potential targets. Results. The expression levels of miR-641 were downregulated, while the expression levels of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were increased in breast cancer cell lines. The in vitro results showed that miR-641 repressed proliferation and migration/invasion and promoted apoptosis of breast cancer cells. NUCKS1, a positive regulator of phosphatidylinositol-3-kinases (PI3K)/protein-serine-threonine kinase (AKT) pathway, was confirmed as a direct target of miR-641. The of treatment of the PI3K agonist, 740Y-P, could abrogate the antioncogenic potentials of miR-641 in breast cancer cells. Conclusion. miR-641 functioned as a tumor suppressor through the PI3K/AKT signaling pathway via targeting NUCKS1 in breast cancer.

Human epidermal growth factor receptor 2 (HER2)‐positive is a particularly aggressive type of the breast cancer. Trastuzumab‐based therapy is a standard treatment for HER2‐positive breast cancer, but some patients are resistance to the therapy. There are no known diagnostic biomarkers to improve the early diagnosis of HER2‐positive breast cancer and the clinical utility of trastuzumab therapy. Using ultrahigh‐performance liquid time of flight mass spectrometry (UPLC‐TOF‐MS)‐based serum metabolomics and multivariate statistical analysis, we investigated and identified the circulating metabolites L‐arginine and arachidonic acid were elevated in trastuzumab‐responsive and trastuzumab‐resistant HER2‐positive breast cancer patients, and increased until reaching their peaks in trastuzumab‐resistant HER2‐positive breast cancer patients. Moreover, an equation for assessing the risk scores based on linear logistic regression models involving L‐arginine and arachidonic acid was created, which was beneficial for revealing metabolic changes in HER2‐positive breast cancer and enhancing current trastuzumab‐based therapy. In summary, we develop serum‐based metabolic biomarkers for diagnosis of HER2‐positive breast cancers and predicts the therapeutic effects of trastuzumab therapy.