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Right ventricular (RV) failure determines the prognosis in pulmonary arterial hypertension (PAH), but the underlying mechanism is still unclear. Growing evidence has shown that microRNAs participate in RV remodeling. This study is undertaken to explore the role of miR-335-5p in regulating RV remodeling induced by PAH. Two PAH models were used in the study, including the monocrotaline rat model and hypoxia/su5416 mouse model. miRNA sequencing and RT-qPCR validation identified that miR-335-5p was elevated in the RV of PAH rats. In vitro, miR-335-5p expression was increased after angiotensin II treatment, and miR-335-5p inhibition relieved angiotensin II-induced cardiomyocyte hypertrophy. The luciferase reporter assay showed that calumenin was a target gene for miR-335-5p. Pretreatment with miR-335-5p inhibitors could rescue calumenin downregulation induced by angiotensin II in H9C2 cells. Moreover, intracellular Ca2+ concentration and apoptosis were increased after angiotensin II treatment, and miR-335-5p inhibition decreased intracellular Ca2+ accumulation and apoptosis. Finally, in vivo miR-335-5p downregulation (antagomir miR-335-5p) attenuated RV remodeling and rescued calumenin downregulation under conditions of hypoxia/su5416 exposure. Our work highlights the role of miR-335-5p and calumenin in RV remodeling and may lead to the development of novel therapeutic strategies for right heart failure. [ABSTRACT FROM AUTHOR]

The CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) plays an extremely important role of the programed death receptor ligand-1 (PD-L1) protein. Our study is aimed at investigating the expression of CMTM6 and PD-L1 proteins in triple-negative breast cancer and their correlation with the clinical pathological data of patients. We selected 89 cases of triple-negative breast cancer and 62 cases of normal breast tissue specimens. Immunohistochemical methods were used to detect the expression levels of CMTM6 and PD-L1 and to carefully study differences in their expression. The expression of CMTM6 and PD-L1 in TNBC was higher than that in normal breast tissue, and the expression of the two was positively correlated (p < 0.05). In TNBC, CMTM6 expression is positively correlated with tumor size, lymph node metastasis, Ki67 proliferation index, and TNM stage (p < 0.05). PD-L1 expression is positively correlated with tumor size, lymph node metastasis, Ki67 proliferation index, TNM stage, and vascular infiltration (p < 0.05). Kaplan-Meier analysis showed that the positive expression of CMTM6 and PD-L1 had no correlation with the survival rate of patients (p > 0.05). According to KM-plotter, we found that a higher CMTM6 expression was positively related with relapse-free survival rate of patients (p < 0.05). A higher PD-L1 expression was positively correlated with relapse-free, overall, and distant metastasis survival rate of patients (p < 0.05). In timer database, we found a positive correlation between the expression of CMTM6 and PD-L1 in triple-negative breast cancer. Both CMTM6 and PD-L1 are highly expressed in TNBC, and their expressions are positively related. In the future, the two gene might become targets for the treatment of TNBC, providing a basis of clinical treatment of TNBC. [ABSTRACT FROM AUTHOR]

Secreted protein, acidic and rich in cysteine (SPARC, also known as osteonectin), is a small molecule glycoprotein associated with cell secretions. The purpose of our research is to clarify the clinicopathological and prognostic significance of SPARC expression in breast cancer. In this study, we performed a meta-analysis and bioinformatics analysis using the PubMed, Web of Science, Wanfang Data, and CNKI databases. The meta-analysis showed that SPARC expression was elevated in breast cancer tissue, compared with normal tissue, while SPARC expression in tumor stromal cells was higher than that of tumor cells. The expression of SPARC was positively correlated with histological grade and TNM staging. The Kaplan-Meier plotter showed that low SPARC expression was negatively correlated with the overall, postprogression, and distant metastasis survival rates of patients. According to Oncomine database, SPARC expression was upregulated in breast cancer than normal tissues. In TCGA database, univariate analysis showed that lymph node metastasis, distant metastasis, and TNM staging were negatively correlated with patient prognosis in breast cancers. Cox multivariate analysis showed that age, lymph node metastasis, distant metastasis, and TNM staging were important factors affecting the survival time of breast cancer patients. SPARC expression can be employed as a good indicator of prognosis of breast cancer patients, which will provide new methods and ideas of preventive treatment. [ABSTRACT FROM AUTHOR]