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Breast cancer is the most prevalent cancer among women, and diagnosis and treatment represent a substantial challenge due to the lack of adequate molecular targets. It has been shown that long noncoding RNAs (lncRNAs) serve pivotal roles in regulating gene expression in tumors. The roles of long intervening noncoding RNA (Linc)-OIP5 has been demonstrated in different types of cancer; however, its function in breast cancer has not been determined. In the present study, expression of Linc-OIP5, YAP1 (Hippo signaling component) and JAG1 (Notch signaling component) in breast cancer cells with different degrees of malignancy were determined. To assess whether Linc-OIP5 regulated the malignant biological behaviors of MDA-MB-231 cells, its expression was knocked down using a specific small interfering RNA (siRNA), and cell proliferation was determined using a CCK-8 assay, apoptosis was evaluated using an Annexin V-FITC apoptosis detection kit, migration was assessed using a wound healing and transwell migration assays, and cell invasion examined using a transwell invasion assays. The effect of Linc-OIP5 knockdown on YAP1 and JAG1 expression was quantified using reverse transcription-quantitative PCR and immunoblotting. Cell proliferation, migration and invasion were reduced, while apoptosis was increased in MDA-MB-231 cells transfected with Linc-OIP5-specific siRNA. Mechanistic investigations showed that Linc-OIP5 knockdown downregulated YAP1 and JAG1 expression. The results of the present study suggest that Linc-OIP5 affects the malignant biological behaviors of MDA-MB-231 cells, at least partly through its effects on YAP1/JAG1 signaling. Whilst there are a number of mechanisms underlying the pathogenesis of breast cancer, the results of the present study highlight Linc-OIP5 as a potential therapeutic target in breast cancer.

Diabetic patients often have a heightened risk of cardiomyopathy, even in the absence of traditional risk factors such as hypertension and atherosclerotic coronary artery disease. Diabetic cardiomyopathy is characterized by a typical cardiomyopathy specific to diabetes, the pathogenesis of which has yet to be fully elucidated. As a well-documented oncogenic long noncoding RNA (lncRNA), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in a variety of pathological processes, including diabetic complications. This study aimed to evaluate the functional roles of MALAT1 in the pathogenesis of diabetic cardiomyopathy. Spontaneously diabetic (db/db) C57BL/Ks mice were employed to establish diabetic cardiomyopathy models in vivo and high glucose (HG)-cultured mouse cardiomyocytes for myocardial damage models in vitro. Mouse left ventricular volume and function were evaluated by echocardiography, while the myocyte cross-sectional area was calculated to evaluate the degree of myocardial hypertrophy. TUNEL staining and flow cytometric analysis were performed to evaluate myocardial damage and cardiomyocyte apoptosis. Silencing of MALAT1 was found to attenuate cardiac dysfunction and inhibit cardiomyocyte apoptosis in db/db mice and HG-cultured mouse cardiomyocytes. MALAT1 recruited the histone methyltransferase EZH2 to the miR-22 promoter region and inhibited its expression. EZH2 induced an increased in the expression of ATP-binding cassette transporter A1 (ABCA1), which was identified to be a target gene of miR-22. Silencing of EZH2 was found to improve cardiac function and prevent cardiomyocyte apoptosis in db/db mice and HG-cultured mouse cardiomyocytes in the presence of MALAT1, suggesting that MALAT1 mediated myocardial damage by recruiting EZH2 to the miR-22 promoter. Taken together, this study's findings provide evidence confirming our hypothesis, suggesting the involvement of MALAT1 in the processes of cardiac function and cardiomyocyte apoptosis via the EZH2/miR-22/ABCA1 signaling cascade, which has potential therapeutic implications for the understanding of diabetic cardiomyopathy.

Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications of diabetes mellitus independent of hypertension, coronary disease, and other heart diseases. The development of DCM is multifactorial and hard to detect at an early stage. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is emerging as a regulator of DCM, the underlying mechanism of its role in DCM has not been elaborated yet. In this study, we established a mouse DCM model via streptozocin injection as evidenced by cell hypertrophy and cell apoptosis of myocardial tissue, and found that Malat1 expression was upregulated in the myocardium in DCM mice. Meanwhile, elevated expression of pro-apoptotic factors p53, p21, cleaved caspase 3, cleaved caspase 9 and BAX, and down-regulation of anti-apoptotic BCL-2 were observed in DCM myocardium. We further investigated the effect of Malat1 on cardiomyocytes under high glucose condition by silencing Malat1 with its specific short-hairpin RNA. Like in vivo, expression of Malat1 in cardiomyocytes was notably raised, remarkable cell apoptosis and changes in apoptosis-related factors were also observed following high glucose treatment. Besides, we validated that Malat1 acted as a sponge of miR-181a-5p. Inhibition of miR-181a-5p could, at least partially, abolish Malat1 knockdown-induced alteration in cardiomyocytes. In addition, p53, a critical regulator of apoptosis, was validated to be a downstream target of miR-181a-5p. In summary, our findings reveal that Malat1 knockdown attenuates high glucose-induced cardiomyocyte apoptosis via releasing miR-181a-5p, and this mechanism may provide us with new diagnosis target of DCM.

Diabetic cardiomyopathy (DCM) is defined as ventricular dysfunction occurring independently of a recognized cause such as hypertension or coronary artery disease. Liver X receptor α (LXRα), a subtype of ligand-activated transcription factors LXRs, has been considered as a potential pharmacological target in the pathogenesis of cardiovascular and metabolic diseases. However, the potential mechanism of how LXRα is regulated in cardiomyocytes is still unclear. This study investigated the effect of activating LXRα with GW3965 on cardiomyocyte apoptosis and its upstream regulator in glucose-induced H9C2 cells. Our data indicated that GW3965 up-regulated the expression of LXRα, inhibited cardiomyocyte apoptosis, and altered the apoptosis-related proteins in glucose-induced H9C2 cells. In addition, GW3965 restored the mitochondrial membrane potential level and decreased the ROS production induced by glucose. Moreover, LXRα was confirmed as a direct target of microRNA-1 (miR-1) that was involved in cardiomyocyte apoptosis of DCM, and overexpression of miR-1 abrogated the inhibiting effect of GW3965 on glucose-induced apoptosis in H9C2 cells. This study highlights an important role of LXRα in the development of DCM and brings new insights into the complex mechanisms involved in the pathogenesis of DCM.

Diabetic cardiomyopathy (DCM) is a progressive disease of the heart muscle and the third most common cause of heart failure. In the present study, we evaluated the effects of bone marrow‑derived endothelial progenitor cell (EPC) transplantation on the development of DCM in a streptozotocin (STZ)-induced diabetic rat model. Ex vivo generated, characterized and cultivated rat EPCs were identified by flow cytometry of their surface markers. EPCs were transplanted intravenously into rats through the tail vein 6 weeks after they were challenged with STZ and the rats were sacrificed 4 weeks later. Before sacrifice, left ventricular (LV) catheterization was performed to evaluate the cardiac function. Myocardium sections were stained with Masson's trichrome staining to investigate myocardial collagen contents. Fibrosis-, apoptosis- and oxidative stress-related gene expressions were analyzed by western blot analysis. Transplantation of EPCs alleviated the impaired cardiac function associated with diabetes and decreased the collagen volume in diabetic myocardium resulting in improved cardiac function. Furthermore, EPC transplantation decreased the expression of type I collagen, Bax, caspase-3 and p67phox, while increasing the expression of Bcl-2 and manganese superoxide dismutase (MnSOD). Taken together, our results suggest that transplantation of EPCs improved cardiac function in the rat DCM model, likely through inhibition of cardiomyocyte apoptosis and attenuating myocardial fibrosis.

The present study was designed to investigate the myocardial expression of liver X receptor alpha (LXRα) in a streptozotocin (STZ)-induced diabetic rat model. Immunohistochemical staining, quantitative real-time RT-PCR, and Western blot analysis were used to determine the expression of LXRα in the myocardium of STZ-induced diabetic rats. The myocardial expression of LXRα target genes, long-chain acyl-CoA synthetase 3 (ACSL3), fatty acid transporter protein (FAT/CD36), ATP-binding cassette transporter A1 (ABCA1), and ABCG1 were also detected. Bisulfite sequencing analysis was employed to examine the methylation status of the CpG island at the LXRα promoter region in the myocardium of STZ-induced diabetic rats. We found that LXRα mRNA and protein expression in the left ventricles, right ventricles, and atria of diabetic rats were gradually increased during the progression of diabetic cardiomyopathy (DCM). The mRNA expression levels of ACSL3 and FAT/CD36 and the protein expression levels of ABCA1 and ABCG1 were also markedly increased in different heart chambers of diabetic rats. Moreover, there was a significant difference in the methylation status of LXRα gene between the ventricles of control and diabetic rats (P