MicroRNA-30d-5p ameliorates lipopolysaccharide-induced acute lung injury via activating AMPKα.

OBJECTIVES: Acute lung injury (ALI) is a devastating lung disease characterized by uncontrolled pulmonary inflammation and oxidative stress. Currently, no effective therapeutic strategies are available for ALI and its prognosis remains poor. The present study aims to investigate the role and potential mechanism of microRNA-30d-5p (miR-30d-5p) in the progression of ALI. METHODS: Mice were intravenously treated with miR-30d-5p agomir, antagomir or their respective controls for 3 consecutive days and then were exposed to a single intratracheal injection of lipopolysaccharide (LPS) for 12 h at a dosage of 5 mg/kg to induce ALI. To inhibit adenosine monophosphate-activated protein kinase α (AMPKα) or phosphodiesterase 4 D (PDE4D), compound C (CpC) and rolipram were used. RESULTS: miR-30d-5p expression in the lungs was significantly inhibited by LPS treatment. miR-30d-5p agomir significantly alleviated, while miR-30d-5p antagomir aggravated pulmonary inflammation, oxidative damage, and dysfunction in ALI mice. Besides, we found that miR-30d-5p agomir ameliorated LPS-induced ALI via activating AMPKα and that the inhibition of AMPKα by CpC completely abolished these beneficial effects of miR-30d-5p agomir. Further findings validated that PDE4D downregulation was required for the activation of AMPKα by miR-30d-5p agomir. CONCLUSION: miR-30d-5p ameliorates LPS-induced ALI via activating AMPKα and it is a valuable therapeutic candidate in the treatment of ALI.

FOXC2-AS1 stabilizes FOXC2 mRNA via association with NSUN2 in gastric cancer cells.

Long noncoding RNA (lncRNA) FOXC2-AS1 has been reported to act as an oncogene in multiple human cancers. However, the clinical significance, functional role and underlying mechanism of FOXC2-AS1 in gastric cancer (GC) remains largely unknown. Here, we found that FOXC2-AS1 expression was significantly elevated in GC tissues and cells, and overexpression of FOXC2-AS1 indicated advanced TNM stage and shorter overall survival in GC patients. Functionally, knockdown of FOXC2-AS1 attenuated the proliferation, migration and invasion of GC cells, whereas overexpression of FOXC2-AS1 showed the opposite effects. Further investigation revealed that FOXC2-AS1 interacted with FOXC2 mRNA and repressed its degradation. FOXC2-AS1 recruited RNA methyltransferase NSUN2 to FOXC2 mRNA, increasing its m5C level and association with YBX1. Taken together, our findings suggested that FOXC2-AS1 acted as an oncogenic lncRNA by stabilizing FOXC2 mRNA in an m5C-dependent manner, which may provide a novel therapeutic target for GC.

miR­351­5p aggravates lipopolysaccharide­induced acute lung injury via inhibiting AMPK.

Inflammation and oxidative stress have indispensable roles in the development of acute lung injury (ALI). MicroRNA (miRNA/miR)­351­5p was initially identified as a myogenesis­associated miRNA; however, its role in lipopolysaccharide (LPS)­induced ALI remains unclear. The aim of the present study was to investigate the role and potential mechanisms of miR­351­5p in ALI. ALI was induced through a single intratracheal injection of LPS for 12 h, and miR­351­5p agomir, antagomir or their corresponding negative controls were injected into the tail vein before LPS stimulation. Compound C, 2',5'­dideoxyadenosine and H89 were used to inhibit AMP­activated protein kinase (AMPK), adenylate cyclase and protein kinase A (PKA), respectively. miR­351­5p levels in the lungs were significantly increased in response to LPS injection. miR­351­5p antagomir alleviated, while miR­351­5p agomir aggravated LPS­induced oxidative stress and inflammation in the lungs. The present results also demonstrated that miR­351­5p antagomir attenuated LPS­induced ALI via activating AMPK, and that the cAMP/PKA axis was required for the activation of AMPK by the miR­351­5p antagomir. In conclusion, the present study indicated that miR­351­5p aggravated LPS­induced ALI via inhibiting AMPK, suggesting that targeting miR­351­5p may help to develop efficient therapeutic approaches for treating ALI.

[Expressions of Cyr61 and WISP-3 in non-small cell lung cancer and its clinical significance].

BACKGROUND: Cysteine-rich protein 61 (Cyr61) plays a role as a tumor suppressor in non-small cell lung cancer (NSCLC). Cyr61 and WISP-3 have a very significant sequence homology, belonging to the same CCN gene family. The aim of this study is to investigate the expressions of Cyr61 and WISP-3 in NSCLC, and explore the relationship between their expressions and tumor's clinicopathological characteristics. METHODS: The expressions of Cyr61 and WISP-3 were detected in 54 cases with primary NSCLC and their corresponding normal lung tissues in control group by immunohistochemical staining (SP), and the clinical data were analyzed. RESULTS: Down-regulation of Cyr61 and up-regulation of WISP-3 were both found in lung cancer tissue compared with the corresponding normal lung tissue (both P < 0.001); The expression of Cyr61 was negatively correlated with the expression of WISP-3 (r=-0.395, P=0.003); Cyr61 expression levels was closely correlated with tumor grade, tumor type, clinical stage, family history, smoking and metastasis (P < 0.05). Also, WISP-3 was closely correlated with tumor grade, clinical stage and age (P < 0.05). CONCLUSIONS: The expressions of Cyr61 and/or WISP-3 may be important biological markers in reflecting the progression, biological behaviors, metastatic potential and prognosis of NSCLC.