Erratum: microRNAs carried by exosomes promote epithelial-mesenchymal transition and metastasis of liver cancer cells.

[This corrects the article on p. 6811 in vol. 12, PMID: 33194074.].

microRNAs carried by exosomes promote epithelial-mesenchymal transition and metastasis of liver cancer cells.

In this study, transforming growth factor-ß1 treatment effectively induced epithelial-mesenchymal transition (EMT) of SMMC-7721 cells, and the expression and function of microRNAs (miRNAs) were determined to understand the processes involved in liver cancer metastasis. Nanoparticle tracking analysis and western blotting were performed to identify exosomes. Transwell and MTS assays were used to assess cell migration and proliferation, respectively. Immunofluorescence microscopy was used to identify the metastasis of exosomes in cells. High-throughput sequencing was used to identify mRNAs and miRNAs in cells and exosomes, respectively. The identified differentially expressed miRNAs (DEmis) were further confirmed using quantitative real-time polymerase chain reaction. An miRNA-target mRNA interaction network was constructed using Cytoscape_V2_8_3. SPSS version 16.0 software with one-way analysis of variance was used for statistical analysis. P < 0.05 was considered statistically significant. The overall size of exosomes in EMT SMMC-7721 cells was smaller than that in normal SMMC-7721 cells. Exosomes of EMT SMMC-7721 cells could promote cell migration and invasion in several cell lines. We identified differentially expressed mRNAs (DEms) and DEmis. Among them, a total of 60 and 78 DEms were upregulated and downregulated, respectively, in EMT SMMC-7721 cells compared with those in SMMC-7721 cells. A total of 709 and 123 DEmis were upregulated and downregulated, respectively, in exosomes in EMT SMMC-7721 cells compared with those in SMMC-7721 cells. hsa-miR-24-3p and hsa-miR-21-5p were further selected for knockdown experiments. Exosomes in cells with hsa-miR-24-3p knockdown could effectively inhibit EMT. hsa-miR-24-3p may be one of the most important molecular markers for EMT in liver cancer, which provides novel clues for the mechanisms involved in liver cancer metastasis.

The type 1 phosphatase Reg1p-Glc7p is required for the glucose-induced degradation of fructose-1,6-bisphosphatase in the vacuole.

Protein phosphatases play an important role in vesicular trafficking and membrane fusion processes. The type 1 phosphatase Glc7p and its regulatory subunit Reg1p were identified as required components in the glucose-induced targeting of the key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) to the vacuole for degradation. The interaction of Reg1p with Glc7p was important for the transport of FBPase from intermediate vacuole import and degradation (Vid) vesicles to vacuoles. The glc7-T152K mutant strain exhibited a reduced Reg1p binding along with defects in FBPase degradation and Vid vesicle trafficking to the vacuole. In this mutant, Vid vesicles were the most defective components, whereas the vacuole was also defective. Shp1p and Glc8p regulate Glc7p phosphatase activity and are required for FBPase degradation. In the Deltashp1 and Deltaglc8 strains, Reg1p-Glc7p interaction was not affected, suggesting that phosphatase activity is also necessary for FBPase degradation. Similar to those seen in the glc7-T152K mutant, the Deltashp1 and Deltaglc8 mutants exhibited severely defective Vid vesicles, but partially defective vacuoles. Taken together, our results suggest that Reg1p-Glc7p interaction and Glc7p phosphatase activity play a required role in the Vid vesicle to vacuole-trafficking step along the FBPase degradation pathway.