This study investigated the effects of chronic intermittent hypoxia (CIH), a model of sleep apnea syndrome (SAS), on cardiac function. SRC-3 was extremely lowly expressed in the adult mouse heart tissue, while SRC-3 was highly expressed in the adult mouse heart tissue after CIH, suggesting that SRC-3 is involved in CIH model. We further studied the role of SRC-3 in CIH-induced myocardial injury in mice. Twenty-four healthy Balb/c male mice ( n = 16 , wild type; n = 8 , SRC-3 knockout (SRC3-KO)) were randomly divided into three groups: air control (Ctrl), CIH, and CIH+SRC3-KO. Mice were exposed to CIH for 12 weeks. qRT-PCR was used to evaluate cardiac expression of the following genes: 11HSD1, 11HSD2, GR, MR, COX-2, OPN, NOX2, HIF-1-α, IL-1β, IL-6, iNOS, TNF-α, PC-1, and TGF-β. Enzymatic levels of SOD, CAT, MDA, NOS, and NO in the mouse hearts were determined using commercially available kits. Immunohistochemistry (IHC) was used to evaluate NF-κB expression in cardiac tissues. A transmission electron microscope (TEM) was used to evaluate myocardial ultrastructure. TUNEL staining was used to assess myocardial cell apoptosis. CIH induced cardiac damage, which was ameliorated in the SRC-3 KO mice. CIH significantly increased the heart-to-body weight ratio, expression of all aforementioned genes except 11HSD1, GR, and MR, and increased the levels of MDA, NOS, NO, and NF-κB, which were attenuated in the SRC-3 KO mice. The CIH group had the lowest SOD and CAT levels, which were partially recovered in the CIH+SRC3-KO group. 11HSD2 gene expression was elevated in both the CIH and CIH+SRC3-KO groups compared to the Ctrl group. The CIH group had severe myocardial cell apoptosis and mitochondrial dysfunction, which were alleviated in the CIH+SRC3-KO group. CIH causes cardiac damage through inducing oxidative stress and inflammation. Knockout of SRC-3 ameliorates CIH-induced cardiac damage through antagonizing CIH-triggered molecular changes in cardiac tissue.

Background and purpose: HOX transcript antisense RNA (HOTAIR) is a long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes can mediate intracellular communication in cancer by transferring active molecules. However, the role and mechanism of HOTAIR in nonsmall cell lung cancer (NSCLC) are still unclear. This study mainly explores the role and mechanism of exosome-derived HOTAIR in NSCLC. Methods: after the material characterization of the CD63 immune lipid magnetic bead (CD63-IMB), the exosomes in serum of NSCLC patients were captured through CD63-IMB for the corresponding biological characterization. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression level of HOTAIR in tumor tissues, serum, and serum exosome from NSCLC patients. Subsequently, exosome secreted by NCI-H1975 cells with highly expressed HOTAIR was selected to treat low-expression A549 cells and HOTAIR knockdown on NCI-H1975 cells. In this way, action mechanisms of HOTAIR can be investigated by means of qRT-PCR, colony formation assays, and flow cytometry. Results: exosomes can be isolated by CD63-IMB, and taken up by cells effectively; the qRT-PCR results demonstrate that HOTAIR expressions are significantly upregulated in tumor tissues, serums, and exosomes isolated from serums of NSCLC patients. Clinicopathological correlation analysis shows that the upregulation of HOTAIR is closely associated with lymphatic metastasis and tumor node metastasis (TNM) staging (P < 0.05). HOTAIR expressions show a significant increase in A549 cells treated with exosomes derived from NCI-H1975 cells, signifying that both proliferation and migration of A549 cells are promoted, and HOTAIR depletion could inhibit the proliferation and migration of lung cancer cells. Conclusions: HOTAIR is highly expressed in tumor tissues, serums, and serum exosomes of NSCLC patients and its expression has a significant correlation with lymphatic metastasis and TNM staging. Moreover, the exosome may promote NSCLC proliferation and migration through HOTAIR transportation. Therefore, exosome-derived HOTAIR is expected to be a new molecular marker for NSCLC diagnosis, and exosomal transmission of HOTAIR may provide a new approach to NSCLC diagnosis.