Study on the Regulation of Trophoblast Activity by Abnormally Expressed lncRNA CCDC144NL-AS1 in Patients with Gestational Diabetes Mellitus

Abstract

Gestational diabetes mellitus (GDM) is a common complication in pregnant women. The growth and differentiation of trophoblast cells determine the function of the placenta, and therefore further affect the transport of nutrients to the fetus. lncRNA Coiled-Coil Domain Containing 144 N-Terminal-Like antisense1 (CCDC144NL-AS1) was reported to be abnormally expressed in GDM, but its function and mechanism remain undefined. This study aimed to reveal the expression of CCDC144NL-AS1 in GDM and evaluate its significance in disease development. The expression of CCDC144NL-AS1 in serum and placenta tissues of GDM patients and healthy pregnant women was evaluated using PCR. The effect of CCDC144NL-AS1 on the proliferation, migration, and invasion of trophoblast cells was evaluated with CCK8 and Transwell assay. The mechanism of the interaction between CCDC144NL-AS1 and miR-143–3p was assessed by luciferase reporter assay and cell transfection. CCDC144NL-AS1 was upregulated in GDM patients, which discriminated GDM patients from healthy pregnant women with high sensitivity and specificity and was positively correlated with the insulin resistance indexes. In trophoblast cells, high glucose exposure induced increased CCDC144NL-AS1 and suppressed cell proliferation, migration, and invasion. Silencing CCDC144NL-AS1 could alleviate the inhibitory effect of high glucose, while the knockdown of miR-143–3p reversed the effect of CCDC144NL-AS1. In conclusion, upregulated CCDC144NL-AS1 served as a diagnostic biomarker of GDM and regulated the development of trophoblast cells via negatively modulating miR-143–3p.

Key words

lncRNA CCDC144NL-AS1 - trophoblast cell - diagnosis - development - gestational diabetes mellitus 

Publication History

Received: 05 January 2023

Accepted after revision: 25 April 2023

Article published online:
09 June 2023

• References

• 1 Ma RCW.. Epidemiology of diabetes and diabetic complications in China. Diabetologia 2018; 61: 1249-1260
• 2 Johns EC, Denison FC, Norman JE. et al. Gestational diabetes mellitus: mechanisms, treatment, and complications. Trends Endocrinol Metab 2018; 29: 743-754
• 3 Alejandro EU, Mamerto TP, Chung G. et al. Gestational diabetes mellitus: a harbinger of the vicious cycle of diabetes. Int J Mol Sci 2020; 21: 5003
• 4 Juan J, Yang H.. Prevalence, Prevention, and lifestyle intervention of gestational diabetes mellitus in China. Int J Environ Res Public Health 2020; 17: 9517
• 5 Silva-Zolezzi I, Samuel TM, Spieldenner J.. Maternal nutrition: opportunities in the prevention of gestational diabetes. Nutr Rev 2017; 75: 32-50
• 6 Sert UY, Ozgu-Erdinc AS.. Gestational diabetes mellitus screening and diagnosis. Adv Exp Med Biol 2021; 1307: 231-255
• 7 Dluski DF, Wolinska E, Skrzypczak M.. Epigenetic changes in gestational diabetes mellitus. Int J Mol Sci 2021; 22: 7649
• 8 Zhang Y, Qu L, Ni H. et al. Expression and function of lncRNA MALAT1 in gestational diabetes mellitus. Adv Clin Exp Med 2020; 29: 903-910
• 9 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; 35: 5125-5139
• 10 Zhang Y, Zhang H, Wu S.. LncRNA-CCDC144NL-AS1 Promotes the development of hepatocellular carcinoma by inducing WDR5 expression via sponging miR-940. J Hepatocell Carcinoma 2021; 8: 333-348
• 11 Zhang L, Chi B, Chai J. et al. LncRNA CCDC144NL-AS1 Serves as a prognosis biomarker for non-small cell lung cancer and promotes cellular function by targeting miR-490-3p. Mol Biotechnol 2021; 63: 933-940
• 12 Zhang C, Wu W, Zhu H. et al. Knockdown of long noncoding RNA CCDC144NL-AS1 attenuates migration and invasion phenotypes in endometrial stromal cells from endometriosis†. Biol Reprod 2019; 100: 939-949
• 13 Wang Y, Guo B, Xiao Z. et al. Long noncoding RNA CCDC144NL-AS1 knockdown induces naïve-like state conversion of human pluripotent stem cells. Stem Cell Res Ther 2019; 10: 220
• 14 He J, Guan J, Liao S. et al. Long Noncoding RNA CCDC144NL-AS1 promotes the oncogenicity of osteosarcoma by acting as a molecular sponge for microRNA-490-3p and thereby increasing HMGA2 expression. Onco Targets Ther 2021; 14: 1-13
• 15 Vitiello D, Patrizio P.. Implantation and early embryonic development: implications for pregnancy. Semin Perinatol 2007; 31: 204-207
• 16 Assaf-Balut C, García de la Torre N, Calle-Pascual AL. et al. Detection, treatment and prevention programs for gestational diabetes mellitus: The St Carlos experience. Endocrinol Diabetes Nutr (Engl Ed) 2020; 67: 342-350
• 17 Anderlová K. Screening for gestational diabetes mellitus. Vnitr Lek 2021; 67: 366-367
• 18 Tieu J, McPhee AJ, Crowther CA. et al. Screening for gestational diabetes mellitus based on different risk profiles and settings for improving maternal and infant health. Cochrane Database Syst Rev 2017; 8: Cd007222
• 19 Filardi T, Catanzaro G, Mardente S. et al. Non-coding RNA: role in gestational diabetes pathophysiology and complications. Int J Mol Sci 2020; 21: 4020
• 20 Li Y, Xu K, Xu K. et al. Roles of identified long noncoding RNA in diabetic nephropathy. J Diabetes Res 2019; 5383010
• 21 Li YX, Long DL, Liu J. et al. Gestational diabetes mellitus in women increased the risk of neonatal infection via inflammation and autophagy in the placenta. Medicine (Baltimore) 2020; 99: e22152
• 22 Knöfler M, Haider S, Saleh L. et al. Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci 2019; 76: 3479-3496
• 23 Carrasco-Wong I, Moller A, Giachini FR. et al. Placental structure in gestational diabetes mellitus. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165535
• 24 Graham CH, Hawley TS, Hawley RG. et al. Establishment and characterization of first trimester human trophoblast cells with extended lifespan. Exp Cell Res 1993; 206: 204-211
• 25 Southern PJ, Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet 1982; 1: 327-341
• 26 Aplin JD. Developmental cell biology of human villous trophoblast: current research problems. Int J Dev Biol 2010; 54: 323-329
• 27 Fan H, Ge Y, Ma X. et al. Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer. Cell Death Dis 2020; 11: 521
• 28 Muralimanoharan S, Maloyan A, Myatt L.. Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: role of miR-143. Clin Sci (Lond) 2016; 130: 931-941
• 29 Li B, Fan J, Chen N.. A novel regulator of type II diabetes: MicroRNA-143. Trends Endocrinol Metab 2018; 29: 380-388
• 30 Li L, Zuo H, Huang X. et al. Bone marrow macrophage-derived exosomal miR-143-5p contributes to insulin resistance in hepatocytes by repressing MKP5. Cell Prolif 2021; 54: e13140
• 31 Bai S, Xiong X, Tang B. et al. Exosomal circ_DLGAP4 promotes diabetic kidney disease progression by sponging miR-143 and targeting ERBB3/NF-kappaB/MMP-2 axis. Cell Death Dis 2020; 11: 1008