Fig. 1 | Signal Transduction and Targeted Therapy

Fig. 1

From: LncRNA Wee1-AS coordinates oxidative fatty acid metabolism through the activation of mitochondrial CDK1/CYCLIN B1

Fig. 1The alternative text for this image may have been generated using AI.

Identification of Wee1-AS which is overexpressed in livers of HFD-fed mice. a Heatmap representing 31 differentially expressed lncRNAs under HFD conditions in male and ovariectomized female mice. Each row corresponds to a single lncRNA, whereas each column represents the mean lncRNA expression of five mice from each experimental group. The scale bar denotes Z-score values, indicating relative lncRNA expression levels. Notably, Wee1-AS expression increased under HFD conditions, as indicated by the arrow. M: Male, F: Female, O: Ovariectomy, L: LFD, H: HFD. b Transcript of Wee1-AS was annotated previously in the NCBI database (AK081893). Wee1-AS transcripts with extra sequences were identified via rapid amplification of cDNA ends (RACE) in this study. The sizes of transcripts are shown in parentheses. The Coding Potential Calculator (https://cpc.gao-lab.org/programs/run_cpc.jsp) generated a negative coding potential score (–0.75), suggesting that the Wee1-AS does not encode a protein. c Relative Wee1-AS expression levels in livers of mice fed a HFD or a western diet (WD). Total RNA was isolated from the liver tissues and the levels of Wee1-AS were measured via qRT‒PCR. The RNA expression was normalized to that of 18srRNA. The values are presented as the means ± SDs (n = 5). The data were analyzed via the Mann‒Whitney test. **P < 0.01. d Single-cell RNA sequencing (scRNA-seq) analysis of liver samples from WD-induced MASLD mice revealed 13 distinct liver cell types, including Hep (hepatocytes), Chol (cholangiocytes), HSC (hepatic stellate cells), Endo (endothelial cells), KC (Kupffer cells), Mono/MDM (monocytes and monocyte-derived macrophages), cDC (conventional dendritic cells), pDC (plasmacytoid dendritic cells), Neu (neutrophils), and ILC (innate lymphoid cells). Normalized expression levels of Wee1-AS across different liver cell types. Redder colors indicate higher average expression within a given cell type, whereas larger dot sizes represent a greater proportion of cells expressing Wee1-AS. e Cytosol- (blue), nucleoplasm- (red), chromatin- (yellow), cytoplasm- (dark blue), and mitochondria- (green) RNAs in subcellular fractions of primary hepatocytes were purified. The RNA levels of Wee1-AS, Rps14, snRNA U1, and Neat1 was analyzed via qRT‒PCR. The proper cellular fractionation was confirmed by the localization of Rps14, snRNA U1, and Neat1. The data are presented as the means ± SDs (n = 4). f Localization of Wee1-AS in liver tissue obtained from mice in the dark cycle was analyzed via FISH. The upper images show the expression patterns of Wee1-AS (red) and c-Kit (green), a unique marker for the pericentral region (white arrow). The lower images provide an enhanced view, emphasizing intense clusters of Wee1-AS signals (red) within cytosol of individual hepatocytes surrounding the central vein (CV). Scale bar, 200 μm. g Gene Ontology (GO) biological process terms related to genes positively correlated with hepatic Wee1-AS expression in LFD- or HFD-fed mice. The bar graph illustrates significant associations between Wee1-AS and various biological processes. Each bar represents the -log10(p value), and the gene number is indicated in parenthesis

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