BackgroundOvarian cancer (OvCa) is one of the most common malignant diseases of the female reproductive system in the world. The majority of OvCa is diagnosed with metastasis in the abdominal cavity. Epithelial-to-mesenchymal transition (EMT) plays a key role in tumor cell metastasis. However, it is still unclear whether long non-coding RNA (lncRNA) is implicated in EMT and influences cell invasion and metastasis in OvCa.ResultsIn this study, using bioinformatcis analysis, we constructed a lncRNA-mediated competing endogenous RNA (ceRNA) network for mesenchymal OvCa and identified lncRNA AP000695.4, which we named pro-transition associated RNA (PTAR). PTAR was significantly up-regulated in the mesenchymal subtype samples compared with the epithelial subtype samples from the TCGA OvCa data sets. In addition, our study showed that PTAR expression was positively correlated with the expression level of ZEB1 in the mesenchymal OvCa samples. Meanwhile, we found that silencing miR-101 promoted cell migration, whereas the overexpression of miR-101 suppressed EMT and cell migration in OvCa cell lines through the regulation of ZEB1. Further analysis showed that enhanced expression of PTAR promoted EMT and metastasis through the regulation of miR-101, whereas silencing PTAR led to the attenuation of TGF-β1-induced tumorigenicity in ovarian cancer cells. Mechanistically, we found that PTAR acted as a ceRNA of miR-101, as forced expression of PTAR reduced the expression and activity of miR-101. More importantly, the knockdown of PTAR reduced tumorigenicity and metastasis in vivo.ConclusionsTaken together, the results from our study highlight a role for the PTAR-miR-101-ZEB1 axis in OvCa, which offers novel strategies for the prevention of metastasis in OvCa.

More evidence is emerging of the roles long non-coding RNAs (lncRNAs) play as regulatory factors in a variety of biological processes, but the mechanisms underlying the function of lncRNAs in acute myocardial infarction (AMI) have not been explicitly delineated. The present study identified the lncRNA 2810403D21Rik/AK007586/Mirf (myocardial infarction-regulatory factor), that inhibited macroautophagy/ autophagy by modulating Mir26a (microRNA 26a). Inhibition of Mir26a led to cardiac injury both in vitro and in vivo, whereas overexpression of Mir26a attenuated ischemic stress-induced cell death by activating autophagy through targeting Usp15 (ubiquitin specific peptidase 15). More importantly, 2810403D21Rik/Mirf acted as a competitive endogenous RNA (ceRNA) of Mir26a; forced expression of 2810403D21Rik/Mirf downregulated Mir26a to inhibit autophagy. In contrast, loss of 2810403D21Rik/Mirf resulted in upregulation of Mir26a to promote autophagy and alleviate cardiac injury, which in turn improved cardiac function in MI mice. This study identified a lncRNA 2810403D21Rik/Mirf that functions as an anti-autophagic molecule via ceRNA activity toward Mir26a. Our findings suggest that knockdown of 2810403D21Rik/Mirf might be a novel therapeutic approach for cardiac diseases associated with autophagy.

Long non-coding RNAs (lncRNAs) have been reported to be involved in various pathophysiological processes in many diseases. However, the role and mechanism of lncRNAs in idiopathic pulmonary fibrosis (IPF) have not been explicitly delineated. In the present study, we reported that lncRNA NONMMUT065582, designated pulmonary fibrosis-associated RNA (PFAR), is upregulated in the lungs of mice with lung fibrosis as well as in fibrotic lung fibroblasts. Overexpression of PFAR promoted fibrogenesis through modulation of miR-138, whereas knockdown of PFAR attenuated TGF-β1-induced fibrogenesis in lung fibroblasts. In addition, knockdown of miR-138 promoted fibrogenesis by targeting regulation of yes-associated protein 1 (YAP1), whereas enhanced expression of miR-138 attenuated fibrogenesis in lung fibroblasts. Mechanistically, PFAR acted as competing endogenous RNA (ceRNA) of miR-138: forced expression of PFAR reduced the expression and activity of miR-138 to activate YAP1 and promote fibrogenesis in lung fibroblasts, whereas loss of YAP1 abrogated the pro-fibrotic effect of PFAR. More importantly, PFAR silencing alleviated BLM-induced lung fibrosis in mice. Taken together, the results of our study identified lncRNA PFAR as a new pro-fibrotic molecule that acts as a ceRNA of miR-138 during lung fibrosis and demonstrated PFAR as a novel therapeutic target for the prevention and treatment of lung fibrosis.