Erratum: MicroRNA-506-3p targets SIRT1 and suppresses AMPK pathway activation to promote hepatic steatosis.

[This corrects the article DOI: 10.3892/etm.2021.10865.].

M6A-mediated up-regulation of LncRNA LIFR-AS1 enhances the progression of pancreatic cancer via miRNA-150-5p/ VEGFA/Akt signaling.

N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. There is extensive evidence indicating that long non-coding RNAs (lncRNAs) serve as key regulators of oncogenesis and tumor progression in humans. Through prior study has assessed that LIFR-AS1 plays a key role in various kinds of malignant tumors. However, the exact role of m6A induced LIFR-AS1 in pancreatic cancer (PC) and its potential molecular mechanisms remain largely unknown. In this study, we determined that PC cell lines and tumors exhibit increased LIFR-AS1 expression that correlates with larger tumor size, lymph node metastasis, and more advanced TNM stage. Functionally, loss-of-function studies indicated that LIFR-AS1 knockdown decreased the proliferation, migration, and invasion of PC cells in vitro. Mechanistically, we found that METTL3 induced m6A hyper-methylation on the 3' UTR of LIFR-AS1 to enhance its mRNA stability and LIFR-AS1 could directly interact with miR-150-5p, thereby indirectly up-regulating VEGFA expressions within cells. Through rescue experiments, we were able to confirm that the unfavorable impact of LIFR-AS1 knockdown on VEGFA /PI3K/Akt Signaling could be reversed via the inhibition of miR-150-5p expression. Together, these findings indicate that a noval m6A-LIFR-AS1 axis promotes PC progression at least in part via regulation of the miR-150-5p/VEGFA axis, indicating that this regulatory axis may be a viable clinical target for the treatment of PC.

MicroRNA-506-3p targets SIRT1 and suppresses AMPK pathway activation to promote hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is a complex type of liver disease that represents an important global health threat. The mechanistic basis of this disease remains incompletely understood. The present study sought to explore whether microRNA (miR)-506-3p served a functional role in the onset and/or progression of NAFLD. To that end, high levels of glucose were used to treat liver cancer cell lines (HepG2 and Huh7) to model hepatic steatosis, and the expression levels of miR-506-3p and its downstream target genes were assessed. The cells of this hepatic steatosis model were transfected with miR-506-3p mimic molecules to explore the effect of miR-506-3p overexpression on cell viability, target gene expression and AMP-activated protein kinase (AMPK) phosphorylation. Via bioinformatics approaches, sirtuin 1 (SIRT1) was identified as a potential miR-506-3p target gene with relevance in NAFLD, and this interaction was confirmed via luciferase reporter assay. In the hepatic steatosis model of the present study, miR-506-3p expression level was significantly increased, whereas SIRT1 mRNA/protein levels and AMPK phosphorylation levels were markedly decreased. Transfection of the cells with miR-506-3p mimics led to significant SIRT1 downregulation, while miR-506-3p inhibitor molecules exhibited the opposite effect, with similar trends observed in the phosphorylation status of AMPK. These results suggested that miR-506-3p can inhibit SIRT1 expression and associated AMPK phosphorylation in HepG2 and Huh7 cells in an in vitro hepatic steatosis model system. These data indicated that the miR-506-3p/SIRT1/AMPK axis may be valuable as a therapeutic target in patients affected by NAFLD.

MicroRNA-520f-3p inhibits proliferation of gastric cancer cells via targeting SOX9 and thereby inactivating Wnt signaling.

MicroRNAs (miRNAs) are known to be important in a variety of cancer types. The specific expression and roles of miR-520f-3p in the context of gastric cancer (GC), however, remains unknown. Herein we determined miR-520f-3p expression to be significantly reduced in human GC cells compared to cells of the gastric epithelium, with comparable down-regulation also being evident in gastric cancer tissue samples and the low expression of this miRNA was positively correlated with features of more aggressive large tumor size (p = 0.019), depth of invasion (p = 0.008), and distant metastasis (p = 0.037). We further found that lower levels of miR-520f-3p corresponded with poorer GC patient overall (p = 0.003) and disease-free (p = 0.036) survival. When over-expressed in GC cells, miR-520f-3p was able to impair their growth, proliferation, and survival, instead leading to the induction of apoptosis. We further found that miR-520f-3p was able to bind the SOX9 3'-UTR, thereby negatively regulating its expression in GC cells. Consistent with this model, SOX9 and miR-520f-3p expression were negatively correlated with one another in GC tissues. When SOX9 was upregulated, this was also able to abrogate miR-520f-3p-mediated inactivation of Wnt/ß-catenin signaling. Together our findings thus suggest that miR-520f-3p can act to suppress GC progression, at least in part via suppressing SOX9 expression and thus disrupting Wnt/ß-catenin signaling. Our results thus highlight potential novel therapeutic targets in GC worthy of future investigation.