open access
Plasma Lnc-UCA1/miR-138 axis as a potential biomarker for gestational diabetes mellitus and neonatal prognosis


- Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, Affiliated Hospital of Tongji Medical College, Huazhong University of Science and Technology. Wuhan, China
open access
Abstract
Objectives: This study aimed to explore the correlations of Lnc-UCA1/miR-138 axis with gestational diabetes mellitus (GDM) risk and neonatal prognosis.
Material and methods: First, the blood samples from sixty GDM patients and 60 healthy pregnant women were collected to detect the change of Lnc-UCA1/miR-138 axis by using real-time polymerase chain reaction (RT-qPCR). The clinical characteristics of GDM patients, healthy controls, and neonates were recorded. Then, the correlation analysis of Lnc-UCA1, miR-138, and Lnc-UCA1/miR-138 axis levels with clinicopathological characteristics was performed to explore the clinical value of Lnc-UCA1/miR-138 axis in GDM. Finally, the specificity and sensitivity of Lnc-UCA1, miR-138, and Lnc-UCA1/miR-138 axis for GDM diagnosis was evaluated using receiver operating characteristic (ROC) curves.
Results: Our present study found that, when compared with healthy pregnancies, the expression levels of Lnc-UCA1 and miR-138 were increased and decreased, respectively, and Lnc-UCA1/miR-138 axis profile was elevated. Second, Lnc-UCA1 and Lnc-UCA1/miR-138 axis were positively correlated with fasting glucose, one-hour glucose, and two-hour glucose, while miR-138 showed the opposite trend. Furthermore, the area under the ROC curve (AUC) were 0.8196, 0.8021, and 0.8901 for diagnostic efficiencies of Lnc-UCA1, miR-138, and Lnc-UCA1/miR-138, respectively. In addition, higher profiles of Lnc-UCA1 were correlated with birth asphyxia of neonate.
Conclusions: Circulating Lnc-UCA1/miR-138 axis might be involved in the pathogenesis of GDM and could function as a novel and effective biomarker for GDM risk and neonatal prognosis.
Abstract
Objectives: This study aimed to explore the correlations of Lnc-UCA1/miR-138 axis with gestational diabetes mellitus (GDM) risk and neonatal prognosis.
Material and methods: First, the blood samples from sixty GDM patients and 60 healthy pregnant women were collected to detect the change of Lnc-UCA1/miR-138 axis by using real-time polymerase chain reaction (RT-qPCR). The clinical characteristics of GDM patients, healthy controls, and neonates were recorded. Then, the correlation analysis of Lnc-UCA1, miR-138, and Lnc-UCA1/miR-138 axis levels with clinicopathological characteristics was performed to explore the clinical value of Lnc-UCA1/miR-138 axis in GDM. Finally, the specificity and sensitivity of Lnc-UCA1, miR-138, and Lnc-UCA1/miR-138 axis for GDM diagnosis was evaluated using receiver operating characteristic (ROC) curves.
Results: Our present study found that, when compared with healthy pregnancies, the expression levels of Lnc-UCA1 and miR-138 were increased and decreased, respectively, and Lnc-UCA1/miR-138 axis profile was elevated. Second, Lnc-UCA1 and Lnc-UCA1/miR-138 axis were positively correlated with fasting glucose, one-hour glucose, and two-hour glucose, while miR-138 showed the opposite trend. Furthermore, the area under the ROC curve (AUC) were 0.8196, 0.8021, and 0.8901 for diagnostic efficiencies of Lnc-UCA1, miR-138, and Lnc-UCA1/miR-138, respectively. In addition, higher profiles of Lnc-UCA1 were correlated with birth asphyxia of neonate.
Conclusions: Circulating Lnc-UCA1/miR-138 axis might be involved in the pathogenesis of GDM and could function as a novel and effective biomarker for GDM risk and neonatal prognosis.
Keywords
LncRNA; miRNA; gestational diabetes mellitus; disease severity


Title
Plasma Lnc-UCA1/miR-138 axis as a potential biomarker for gestational diabetes mellitus and neonatal prognosis
Journal
Issue
Article type
Research paper
Published online
2022-06-10
Page views
408
Article views/downloads
255
DOI
10.5603/GP.a2022.0052
Pubmed
Keywords
LncRNA
miRNA
gestational diabetes mellitus
disease severity
Authors
Bingjie Leng
Feifei Chen
Min Li
Heng Yin
Guoqiang Sun
Yun Zhao


- WHO. Definition, diagnosis and classification of diabetes mellitus and its complications; World Health Organization: Geneva, Switzerland, 1999. http://apps.who.int/iris/handle/10665/66040 (12 January 2018).
- International Diabetes Federation. IDF diabetes atlas — across the globe. http://diabetesatlas.org/across-the-globe.html (6 July 2018).
- Wu L, Cui L, Tam WH, et al. Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis. Sci Rep. 2016; 6: 30539.
- Barbour LA, McCurdy CE, Hernandez TL, et al. Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care. 2007; 30(Suppl 2): S112–S119.
- Young BC, Ecker JL. Fetal macrosomia and shoulder dystocia in women with gestational diabetes: risks amenable to treatment? Curr Diab Rep. 2013; 13(1): 12–18.
- American Diabetes Association. Abridged for primary care providers. Clin Diabetes. 2018; 36(1): 14–37.
- Tieu J, McPhee AJ, Crowther CA, et al. Screening and subsequent management for gestational diabetes for improving maternal and infant health. Cochrane Database Syst Rev. 2014(2): CD007222.
- Plaisance V, Abderrahmani A, Perret-Menoud V, et al. MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem. 2006; 281(37): 26932–26942.
- Georgiou HM, Lappas M, Georgiou GM, et al. Screening for biomarkers predictive of gestational diabetes mellitus. Acta Diabetol. 2008; 45(3): 157–165.
- Li T, Hu D, Gong Y. Identification of potential lncRNAs and co-expressed mRNAs in gestational diabetes mellitus by RNA sequencing. J Matern Fetal Neonatal Med. 2021 [Epub ahead of print]: 1–15.
- Cao M, Zhang Le, Lin Yu, et al. Differential mRNA and long noncoding RNA expression profiles in umbilical cord blood exosomes from gestational diabetes mellitus patients. DNA Cell Biol. 2020; 39(11): 2005–2016.
- Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012; 9(6): 703–719.
- Wang CJ, Zhu CC, Xu J, et al. Correction to: The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs. Mol Cancer. 2019; 18(1): 129.
- Yu Q, Zhao MW, Yang Pu. LncRNA UCA1 suppresses the inflammation via modulating miR-203-mediated regulation of MEF2c/NF-κB signaling pathway in epilepsy. Neurochem Res. 2020; 45(4): 783–795.
- Yang JL, Han NH. LncRNA UCA1 stimulates the repair of hyperglycemic vascular smooth muscle cells through targeting miR-582-5p. Eur Rev Med Pharmacol Sci. 2020; 24(24): 12859–12866.
- Liu J, Luo C, Zhang C, et al. Upregulated lncRNA UCA1 inhibits trophoblast cell invasion and proliferation by downregulating JAK2. J Cell Physiol. 2020; 235(10): 7410–7419.
- Luan B, Sun C. MiR-138-5p affects insulin resistance to regulate type 2 diabetes progression through inducing autophagy in HepG2 cells by regulating SIRT1. Nutr Res. 2018; 59: 90–98.
- Qian C, Liang S, Wan G, et al. Salidroside alleviates high-glucose-induced injury in retinal pigment epithelial cell line ARPE-19 by down-regulation of miR-138. RNA Biol. 2019; 16(10): 1461–1470.
- Liu F, Guo J, Qiao Y, et al. MiR-138 plays an important role in diabetic nephropathy through SIRT1-p38-TTP regulatory axis. J Cell Physiol. 2021; 236(9): 6607–6618.
- Ding R, Guo F, Zhang Y, et al. Integrated transcriptome sequencing analysis reveals role of miR-138-5p/TBL1X in placenta from gestational diabetes mellitus. Cell Physiol Biochem. 2018; 51(2): 630–646.
- Xun G, Ma M, Li B, et al. miR-138 and miR-193 target long non-coding RNA UCA1 to inhibit cell proliferation, migration, and invasion of lung cancer. Thorac Cancer. 2020; 11(9): 2681–2689.
- Huang G, Li Li, Liang C, et al. Upregulated UCA1 contributes to oxaliplatin resistance of hepatocellular carcinoma through inhibition of miR-138-5p and activation of AKT/mTOR signaling pathway. Pharmacol Res Perspect. 2021; 9(1): e00720.
- American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2017; 40(Suppl 1): S11–S24.
- Poy MN, Eliasson L, Krutzfeldt J, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004; 432(7014): 226–230.
- Latreille M, Hausser J, Stützer I, et al. MicroRNA-7a regulates pancreatic β cell function. J Clin Invest. 2014; 124(6): 2722–2735.
- Krützfeldt J, Stoffel M. MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab. 2006; 4(1): 9–12.
- Adam S, Elfeky O, Kinhal V, et al. Review: Fetal-maternal communication via extracellular vesicles - Implications for complications of pregnancies. Placenta. 2017; 54: 83–88.
- Liu Y, Zhou D, Li G, et al. Long non coding RNA-UCA1 contributes to cardiomyocyte apoptosis by suppression of p27 expression. Cell Physiol Biochem. 2015; 35(5): 1986–1998.
- Geng JF, Liu X, Zhao HB, et al. LncRNA UCA1 inhibits epilepsy and seizure-induced brain injury by regulating miR-495/Nrf2-ARE signal pathway. Int J Biochem Cell Biol. 2018; 99: 133–139.
- Yan H, Yao P, Hu Ke, et al. Long non‐coding ribonucleic acid urothelial carcinoma‐associated 1 promotes high glucose‐induced human retinal endothelial cells angiogenesis through regulating micro‐ribonucleic acid‐624‐3p/vascular endothelial growth factor C. JDiabetes Investig. 2021; 12(11): 1948–1957.
- Luan B, Sun C. MiR-138-5p affects insulin resistance to regulate type 2 diabetes progression through inducing autophagy in HepG2 cells by regulating SIRT1. Nutr Res. 2018; 59: 90–98.
- Xun G, Ma M, Li B, et al. miR-138 and miR-193 target long non-coding RNA UCA1 to inhibit cell proliferation, migration, and invasion of lung cancer. Thorac Cancer. 2020; 11(9): 2681–2689.
- Szmuilowicz ED, Josefson JL, Metzger BE. Gestational diabetes mellitus. Endocrinol Metab Clin North Am. 2019; 48(3): 479–493.
- Zhang H. Mechanism associated with aberrant lncRNA MEG3 expression in gestational diabetes mellitus. Exp Ther Med. 2019; 18(5): 3699–3706.
- Nair S, Jayabalan N, Guanzon D, et al. Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Clin Sci (Lond). 2018; 132(22): 2451–2467.