Background and Aims: Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods: Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results: Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PP-P2CA may be involved in HCC were determined using miR-Walk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions: PP-P2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.
Objective. An increasing risk of developing osteoporosis which is characterized by bone production weakness and microarchitectural deterioration is found among postmenopausal women. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues in response to local disease severity including bone diseases. Herein, we set out to identify candidate miRNAs predictable for osteoporosis incidence in postmenopausal elderly women. Methods. The circulating miRNA expression profiles deposited in the dataset accessioned as GSE201543 were downloaded from the GEO database. The study included 176 postmenopausal women who underwent BMD testing, including 96 women reporting osteoporosis and 70 women reporting normal BMD. All subjects were submitted their serum samples for measurements of bone metabolism markers. Results. The miRNA expression profiles of the GSE201543 dataset were differentially analyzed and found 97 miRNAs being upregulated concomitantly with 31 miRNAs being downregulated in the serum samples between osteoporotic postmenopausal women and postmenopausal women with normal BMD. Osteoporotic postmenopausal women were demonstrated with elevated serum levels of miR-340-5p and miR-506-3p when compared to normal postmenopausal women. Pearson correlation analysis demonstrated that circulating miR-340-5p and miR-506-3p expressions were increased as BAP, β-CTx, and PINP levels increased, but osteocalcin and 25-(OH)VitD levels are declined in osteoporotic postmenopausal women. Results of the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) showed circulating miR-340-5p and miR-506-3p expressions alone or combined together produced 0.843 AUC, 0.851 AUC, and 0.935 AUC, respectively, when used to predict the incidence of osteoporosis in postmenopausal women. Conclusion. Our work suggested that circulating miR-340-5p and miR-506-3p function as osteo-miRNAs in postmenopausal women and may serve as potential noninvasive biomarkers for the incidence of osteoporosis in postmenopausal women.
ing to 2018 statistics, the incidence of prostate cancer continues to rise, ranking fifth among male cancers (Bray et al., 2018). Despite PCa treatment has made significant progress, advanced PCa still imposes a huge social and economic burden (Cassell et al., 2019).Consequently, exploring new potential biomarkers is essential to discover new treatment strategies for prostate cancer. Circular RNAs (circRNAs) are single-stranded endogenous molecules constructed by back-splicing (Li et al., 2020). CircRNAs with high stability are aberrantly expressed in different diseases and hold great potential as cancer biomarkers (Tang & Hann, 2020). Synchronously, circRNAs are implicated in regulating various biological processes in PCa (Wu et al., 2020). For example, circ_0088233 was prominently boosted in PCa tissues through circRNA microarray detection and exerted oncogenic properties in PCa (Deng et al., 2020).Furthermore, interference of circ-ZNF609 impeded tumour metastasis and increased radiosensitivity in PCa via repressing glycolysis (Du et al., 2020). Also, low levels of circular RNA_LARP4 had apparent correlation with the poor prognosis of PCa patients, and its overexpression alleviated the malignant progression of PCa via combining with FOXO3A (Weng et al., 2020). Besides, prior research revealed that circ_0062019 produced by SLC19A1 gene was conspicuously up-regulated in PCa (Xia et al., 2018). Nevertheless, the mechanism underlying circ_0062019 in PCa needs further inquiry.In terms of circRNAs biological functions, circRNAs block the binding of microRNAs (miRNAs) to downstream target genes through functioning as miRNA sponges (Zhong et al., 2018). For
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