BackgroundCircular RNA (circRNA) is involved in the pathological processes of various diseases. CircRNA is more stable than linear RNAs and is expressed in high levels in tissues, making it a better biomarker candidate than linear RNAs. In this study, we aimed to identify potential circRNA biomarkers of gestational diabetes mellitus (GDM).MethodsA retrospective case–control study was conducted using data and samples from women treated at a hospital in China between July 10, 2017, and February 15, 2018. We collected serum samples from 40 healthy pregnant women (controls) and 40 women with GDM (cases) during the second trimester as well as 65 controls and 65 cases during the third trimester of pregnancy. Placenta tissues and neonatal cord blood were each from another 20 cases and 20 controls. We selected six circRNAs (hsa_circRNA_0054633, hsa_circRNA_103410, hsa_circRNA_063981, hsa_circRNA_102682, hsa_circRNA_0018508, and hsa_circRNA_406918) as candidate biomarkers and used quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to measure their concentrations in the serum and placental tissues. The Pearson correlation test was used to assess the correlation between various circRNAs and between circRNA and clinical variables. The area under the receiver operating characteristic (ROC) curve was used to assess the diagnostic value of circRNAs for GDM at each stage.ResultsHsa_circRNA_0054633 was highly expressed in the blood during the second and third trimesters; its expression was also high in the placenta but low in the cord blood (P < 0.05). Hsa_cirRNA_0054633 was highly correlated with GHBA1 and GHBA1c levels in maternal blood samples at various stages of the GDM group (including placental tissue and umbilical cord blood) (P < 0.05). Hsa_circRNA_063981, hsa_circRNA_102682, and hsa_circRNA_103410 were also differentially expressed between the case and control groups at different stages (P < 0.05). There was a strong correlation between hsa_circRNA_0054633 and hsa_circRNA_103410 levels in third-trimester maternal blood (P = 0.000, r = 0.554) and in neonatal umbilical cord blood (P = 0.000, r = 0.866). Hsa_circRNA_0054633 showed a significant diagnostic value in the second and third trimesters of pregnancy, placenta, and cord blood (AUC = 0.793, 0.664, 0.747, and 0.783, respectively, P < 0.001).ConclusionThis study suggests that hsa_cirRNA_0054633 is abnormally expressed in GDM patients and may play a potential role in the development of GDM. The possibility of using circRNAs for the diagnosis of GDM requires additional investigation in future studies.Electronic supplementary materialThe online version of this article (10.1186/s13148-019-0610-8) contains supplementary material, which is available to authorized users.

Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.

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High‐fat diet (HFD) induced hepatic endoplasmic reticulum (ER) stress drives insulin resistance (IR) and steatosis. NK cells in adipose tissue play an important role in the pathogenesis of IR in obesity. Whether NK cells in the liver can induce hepatic ER stress and thus promote IR in obesity is still unknown. We demonstrate that HFD‐fed mice display elevated production of proinflammatory cytokine osteopontin (OPN) in hepatic NK cells, especially in CD49a+DX5– tissue‐resident NK (trNK) cells. Obesity‐induced ER stress, IR, and steatosis in the liver are ameliorated by ablating NK cells with neutralizing antibody in HFD‐fed mice. OPN treatment enhances the expression of ER stress markers, including p‐PERK, p‐eIF2, ATF4, and CHOP in both murine liver tissues and HL‐7702, a human liver cell line. Pretreatment of HL‐7702 cells with OPN promotes hyperactivation of JNK and subsequent decrease of tyrosine phosphorylation of insulin receptor substrate‐1 (IRS‐1), resulting in impaired insulin signaling, which can be reversed by inhibiting ER stress. Collectively, we demonstrate that hepatic NK cells induce obesity‐induced hepatic ER stress, and IR through OPN production.