Bone metastasis of breast cancer makes patients suffer from pain, fractures, spinal cord compression, and hypercalcemia, and is almost incurable. Although the mechanisms of bone metastasis in breast cancers have been studied intensively, novel specific target will be helpful to the development of new therapeutic strategy of breast cancer. Herein, we focused on the microRNA of tumor cell‐derived exosomes to investigate the communication between the bone microenvironment and tumor cells. The expression of miR‐20a‐5p in the primary murine bone marrow macrophages (BMMs), MCF‐10A, MCF‐7, and MDA‐MB‐231 cell lines, as well as the cell‐derived exosomes were assessed by qRT‐PCR. Transwell assays were used to evaluate the effects of miR‐20a‐5p on tumor cell migration and invasion. The expression of exosomes marker including CD63and TSG101 was detected by Western Blot. Cell cycle distribution of BMMs was analyzed by flow cytometry. 3‐UTR luciferase reporter assays were used to validate the putative binding between miR‐20a‐5p and SRCIN1. MiR‐20a‐5p was highly expressed in breast tumor tissues and the exosomes of MDA‐MB‐231 cells. MiR‐20a‐5p promoted migration and invasion in MDA‐MB‐231 cells, and the proliferation and differentiation of osteoclasts. MDA‐MB‐231 cell‐derived exosomes transferred miR‐20a‐5p to BMMs and facilitated the osteoclastogenesis via targeting SRCIN1. The present work provides evidence that miR‐20a‐5p transferred from breast cancer cell‐derived exosomes promotes the proliferation and differentiation of osteoclasts by targeting SRCIN1, providing scientific foundations for the development of exosome or miR‐20a‐5p targeted therapeutic intervention in breast cancer progression.
Objectives: Heterotaxy syndrome is a recognized risk factor for surgical cardiac interventions. We evaluated the early- and middle-term results of a surgical intervention for patients with heterotaxy syndrome. Methods: A total of 42 patients with heterotaxy syndrome were enrolled (September 2008 to March 2015). Left and right atrial isomerism were identified in 26% (11 out of 42) and 74% of patients (31 out of 42), respectively. The median age of the patients at the time of surgery was 6.8 months (range: 5 days to 22.3 years). Biventricular repair was completed in 3 patients with left atrial isomerism. Seventeen out of 39 patients who were scheduled for single ventricular repair completed a modified Fontan procedure. Results: The hospital mortality rate was 4.7% (2 out of 42). Another 5 deaths occurred in the remaining survivors following hospital discharge with a follow-up duration of 45.8 ± 23.6 months (range: 13-111 months). The 1-year and 5-year survival rates were 88.1% (37/42) and 83.3% (35/42), respectively. Univariate analysis and multivariate analysis identified pulmonary venous obstruction and atrioventricular valve replacement as additional risk factors for mortality. Conclusions: Right ventricular bypass surgery remains the preferred palliative procedure for patients with heterotaxy syndrome. Based on the current results, the early- and middle-term outcomes are satisfactory.
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