Long noncoding RNA HOXD-AS1 induces epithelial-mesenchymal transition in breast cancer by acting as a competing endogenous RNA of miR-421.

Breast cancer (BCa) is the most common malignant tumor in females. Long noncoding RNAs (lncRNAs) are deregulated in many types of human cancers, including BCa. The purpose of the present study was to examine the expression profile and biological role of HOXD cluster antisense RNA 1 (HOXD-AS1) in BCa. Our results revealed that HOXD-AS1 was upregulated in BCa tissues and cell lines, and high HOXD-AS1 expression was correlated with aggressive clinicopathological characteristics of BCa patients. Further gain-of-function and loss-of-function analysis showed that HOXD-AS1 overexpression promoted, whereas HOXD-AS1 knockdown inhibited BCa cell proliferation, cell cycle progression, migration, and invasion, indicating that HOXD-AS1 may function as a novel oncogene in BCa. Mechanistically, HOXD-AS1 could activate epithelial-mesenchymal transition (EMT) in BCa cells. We further proved that HOXD-AS1 might serve as a competing endogenous RNA of miR-421 in BCa cells, and miR-421 was downregulated and negatively correlated with HOXD-AS1 expression in BCa tissues. Besides, we confirmed that SOX4, a master regulator of EMT, was a direct target gene of miR-421. Further, rescue experiments suggested that miR-421 overexpression partly abrogated the oncogenic role of HOXD-AS1 in BCa cells. Therefore, we shed light on that HOXD-AS1/miR-421/SOX4 axis may be considered as a novel therapeutic target for the treatment of BCa patients.

Overexpression miR-24-3p repressed Bim expression to confer tamoxifen resistance in breast cancer.

Endocrine therapy resistance represents a major challenge to the successful treatment of patients with breast cancer. The development of tamoxifen resistance commonly occurrs during the treatment of patients with breast cancer whereas its underlying mechanisms remain elusive. Here, we found that miR-24-3p regulated tamoxifen sensitivity in breast cancer cells. Forced overexpression of miR-24-3p augmented tamoxifen-induced cell viability inhibition in breast cancer cells, while knockdown of miR-24-3p partially attenuated the cytotoxicity effect of tamoxifen. Moreover, we discovered Bim as a target gene of miR-24-3p in breast cancer cells by RNA immunoprecipitation, quantitative reverse transcription polymerase chain reaction, Western blot, and dual luciferase reporter assay. In our established tamoxifen resistant MCF7 cell line (MCF7/TAM), there was a significant elevation of miR-24-3p and decrease of BIM expression compared with parental MCF7 cells. In addition, the inhibition of miR-24-3p could reverse the tamoxifen resistance of MCF7/TAM cells by the induction of cell apoptosis. Silencing of Bim expression blocked miR-24-3p inhibitor-induced elevation of tamoxifen sensitivity of MCF7/TAM cells. Using tumor tissues from patients with breast cancer, we also found that the expression of miR-24-3p was negatively correlated with Bim mRNA expression. Collectively, our study highlighted the pivotal role of miR-24-3p overexpression in mediating the development of tamoxifen resistance in breast cancer and suggested miR-24-3p might be a predictor or target for patients with breast cancer.

The Association of Occupational Stress and Depressive Symptoms among Employed Persons with Benign Breast Disease: The Mediating Role of Psychological Capital.

BACKGROUND: To evaluate the association between depressive symptoms and occupational stress, and the possibility of psychological capital (PsyCap) in alleviating depressive symptoms and occupational stress, we investigated the mediating role of PsyCap on the association between depressive symptoms and occupational stress among employed persons with benign breast disease (BBD) diagnosed by using ultrasonography. METHODS: A cross-sectional survey was conducted in 371 employed persons with BBD. Self-administered questionnaires, including the items of depressive symptoms, occupational stress, the 24-item Psychological Capital Questionnaire, as well as the age, education, marital status, occupation, monthly income, and weekly working hours, were obtained from all patients. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to measure the depressive symptoms, an effort-reward imbalance model was used to assess occupational stress, while 24-item Psychological Capital Questionnaire measurements were used to measure the PsyCap. Baron and Kenny's technique was used to test the mediating effect of PsyCap. RESULTS: In total, 62% of employed persons with BBD had scores equal to or above the cutoff point (CES-D ≥16). Overcommitment was not significantly correlated with PsyCap (r = -0.096, p = 0.066). Depressive symptoms were positively correlated with the effort-reward ratio (ERR) (ß = 0.327, p < 0.001) in model 2, and it was negatively correlated with PsyCap (ß = -0.339, p < 0.001) in model 3. PsyCap associated with ERR mediated the depressive symptoms. CONCLUSIONS: Besides the medical intervention, the management of depressive symptoms and decrease in occupational stress should be considered to alleviate the depressive symptoms associated with employed persons with BBD. PsyCap is an active resource for relieving depressive symptoms and reducing occupational stress in persons with BBD.

Shear Wave Elastography Imaging for the Features of Symptomatic Carotid Plaques: A Feasibility Study.

OBJECTIVES: Shear wave elastography (SWE) was performed to evaluate the Young's modulus of carotid plaques in patients presenting with cerebrovascular incidents, to estimate the clinical value and feasibility of this approach. METHODS: Sixty-one patients (mean age, 65 years; 45 men) underwent common duplex ultrasonic examination and SWE evaluation. The patients were divided into the symptomatic and asymptomatic groups based on the presence of unilateral focal neurological symptoms. Elasticity and echogenicity of the carotid plaque was assessed by Young's modulus and Gray-Weale classification, respectively. RESULTS: A total of 271 carotid plaques were assessed through duplex ultrasonic examination and SWE imaging. The Bland-Altman test revealed a perfect reproducibility of Young's modulus measurement using SWE. The interframe coefficient of variation was 16% within the 271 plaques. In the 61 representative plaques, significant correlations were found between Gray-Weale classification and mean Young's modulus (r = 0.728, P < .01) when the confounding factors were controlled. The mean Young's modulus of representative plaques in symptomatic group was lower than those in asymptomatic groups (mean Young's modulus: 81 kPa versus 115 kPa; P < .01). Logistic regression combined with receiver operating characteristic analysis suggested increased sensitivity and specificity for the identification of symptomatic carotid plaques when the mean Young's modulus was combined with stenosis rate. CONCLUSIONS: Shear wave elastography can evaluate the Young's modulus of carotid plaque stably, and could serve as an additional method for the detection of symptomatic carotid plaques, which, in combination with common ultrasound, can promote the efficiency of differentiating symptomatic carotid plaques.

The effects of microRNA-126 reduced inflammation and apoptosis of diabetic nephropathy through PI3K/AKT signalling pathway by VEGF.

Gene expression microarray and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of miR-126. In model of diabetic nephropathy, we demonstrated that miR-126 expression was down-regulated, compared with control group. Down-expression of miR-126 promoted cell apoptosis and increased inflammation (as indicated by the levels of IL-1ß, IL-6, IL-18 and TNF-α) of diabetic nephropathy in vitro. miR-126 over-expression led to significant inhibition of cell apoptosis and suppressed inflammation (IL-1ß, IL-6, IL-18 and TNF-α). However, the down-expression of miR-126 suppressed the protein expression of VEGF, PI3K and p-AKT in diabetic nephropathy in vitro. On the contrary, over-expression of miR-126 induced the protein expression of VEGF, PI3K and p-AKT in diabetic nephropathy in vitro. The inhibition of VEGF increased the effect of miR-126 down-expression on apoptosis and inflammation in diabetic nephropathy in vitro. We investigated the specific function of miR-126 in patients with diabetic nephropathy and its possible mechanism.

Computer-assisted ultrasound quantification analysis in fatty liver model of rats.

BACKGROUND: Early detection of nonalcoholic fatty liver disease (NAFLD) shows its significant efficacy in preventing the patients from liver failure. The ultrasonic image quantitative analysis software can assist to diagnose NAFLD in the clinical studies. In this study, we aim to explore new method to evaluate the value of computer-assisted ultrasound in diagnosis and classification of fatty liver via Image J software. METHODS: Forty Sprague-Dawley rats were randomly divided into control group (n=10) and model group (n=30). For model group, the rats received high fat diet and subcutaneous injection of carbon tetrachloride to establish nonalcoholic fatty liver model. Ultrasound and pathological examinations on rats were performed on 4, 8, and 12 weeks. Image J software was used to measure the liver grayscale value (LGV) and renal grayscale value (RGV). The difference between LGV and RGV (LRGV) was analyzed. The diagnostic performance of computer-assisted ultrasound quantification was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: We compared ultrasonic quantization parameters between control and model groups and found that the LGV and LRGV were statistically different between the normal and light fatty livers, light and moderate fatty livers, as well as moderate and severe fatty livers, respectively (P<0.05). There was no significant difference in RGV among these groups (P>0.05). Kappa statistic and Bland-Altman analyses showed the consistency of ultrasonic examination and pathological examination was good in diagnosis of fatty liver. CONCLUSIONS: This study indicated that the computer-assisted ultrasound quantification analysis, with high performance of NAFLD diagnosis like pathological examination, could provide a new and flexible noninvasive method for preclinical pharmacological research and basic research.

MicroRNA-204-3p Attenuates High Glucose-Induced MPC5 Podocytes Apoptosis by Targeting Braykinin B2 Receptor.

BACKGROUND: Previous study has been reported that braykinin B2 receptor (Bdkrb2) involves in high glucose-induced renal and podocytes injuries. However, there have been some studies with contradictory results that Bdkrb2 has a protective effect on hyperglycemia-induced injuries in vivo and in vitro. The purpose of the present study was carried out to further investigate the post-transcriptional regulatory mechanism of microRNA (miR) in high glucose-treated podocytes by targeting Bdkrb2 signaling in vitro. METHODS: The CCK-8 and flow cytometry were performed to measure the cell viability and apoptosis. Gene and protein expression were assayed by RT-qPCR and western blotting, respectively. RESULTS: High glucose treatment decreased cell viability and induced membrane and DNA damage, as well as apoptosis in podocytes. High glucose treatment also increased the expression of Bdkrb2, which was blocked by miR-204-3p mimics transfection in podocytes. Bioinformatics and luciferase reporter activity showed that miR-204-3p was directly targeted to the 3'-untranslated region (3'-UTR) of Bdkrb2. High glucose-induced apoptosis and dysfunction in podocytes were reserved by miR-204-3p mimics transfection, while the effects of miR-204-3p mimics in high glucose-treated podocytes were neutralized by overexpressed Bdkrb2. CONCLUSIONS: These findings suggested that miR-204-3p may play a protective role in high glucose-induced apoptosis and dysfunction in podocytes through down-regulation of Bdkrb2.