Functional Analysis of Serum Long Noncoding RNAs in Patients with Atrial Fibrillation.

Objectives: Long noncoding RNAs (lncRNAs) are closely related to diverse diseases. However, its role in atrial fibrillation (AF) pathogenesis needs further exploration. Design: We performed microarray analysis on the serum samples from 70 healthy volunteers and 70 AF patients. This study was aimed at detecting the levels of serum lncRNAs and mRNAs and bioinformatically analyze them to establish potential marker(s) for AF diagnosis. Receiver operating curve (ROC) and area under the curve (AUC) were employed to address the AF diagnostic power of lncRNAs. Results: In the AF serum samples, 753 lncRNAs and 802 mRNAs (p ≤ 0.05; fold change ≥ 2) were upregulated, and 315 lncRNAs and 153 mRNAs were downregulated, as opposed to healthy serum samples. Using bioinformatic analysis, we analyzed the top 4 differentially expressed (DE) lncRNAs, namely, NR-001587, NR-015407, NR-038455, and NR-038894, and found that the PI3K-AKT cell proliferation signaling pathway was most affected. This was in accordance with our functional analysis of DE mRNAs and adjacent lncRNAs. Notably, the elevated serum NR-001587 levels were strongly associated with AF incidence. Conclusions: Our work highlights the role of lncRNAs in AF pathogenesis and provides a novel serum biomarker for AF diagnosis.

Osteopontin promotes metastasis of intrahepatic cholangiocarcinoma through recruiting MAPK1 and mediating Ser675 phosphorylation of ß-Catenin.

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide in recent decades. Osteopontin (OPN) plays an important role in cancer metastasis, but its functional mechanism in ICC is not clear yet. In this study, we found that OPN level was elevated both in plasma and tumor tissues of ICC patients, which was closely related to a shorter overall survival (OS) and high probability of tumor relapse after curative resection. The gain- and loss-of-function studies determined that OPN could promote ICC growth and metastasis. OPN selectively interacted with ß-Catenin and knockdown of ß-Catenin abrogated the effects induced by OPN. OPN recruited MAPK1 and activated MEK-MAPK1 pathway to mediate the S675 phosphorylation of ß-Catenin and nucleus accumulation, which induced the activation of Wnt signaling. Moreover, a significant correlation between OPN and ß-Catenin was found in ICC tissues. OPN, ß-Catenin, and their combination were independent prognostic indicator for ICC patients. In conclusion, OPN promotes ICC progression through recruiting MAPK1 and activating the Wnt/ß-Catenin pathway and can serve as a novel prognostic marker and therapeutic target for ICC.