Aberrantly Expressed Non-Coding RNAs in the Placenta and Their Role in the Pathophysiology of Gestational Diabetes Mellitus

Figures & data

Table 1 Summary and Functions of Aberrant microRNAs in the Placenta Linked to GDM

Reference	miRNA	Chromosome Location	Status	Sample Size	Species	Cell Line	Direct Target Gene	Function
Zhao 2014^Citation36	miR-518d	19q13.42	Upregulated	N = 80 40 GDM 40 NGT	Human	HEK cells	PPARα	–
Li 2015^Citation22	miR-508-3p	Xq27.3	Upregulated	N = 30 15 GDM 15 NGT	Human	HTR-8 cells	PIKfyve	Role in enhancing EGFR signaling
Muralimanoharan 2016^Citation32	miR-143	5q32	Downregulated in A2GDM	N = 18 6 A1GDM 6 A2GDM 6 NGT	Human	Primary trophoblast cells isolated from A2GDM placenta	HK2	Partially rescues mitochondrial function and reduced levels of glycolytic enzymes in trophoblast cells
Cao 2016^Citation85	miR-98	Xp11.22	Upregulated	N = 395 193 GDM 202 NGT	Human	JEG-3 cells	Mecp2	Enhances the DNA methylation level in placental tissues via Mecp2-Trpc3 pathway
Ding 2018^Citation23	miR-138-5p	16q13	Downregulated	N = 54 28 GDM 26 NG	Human	HTR-8/SVneo cells	TBL1X	Trophoblast dysfunction (↓migration and proliferation)
Wang 2018^Citation26	miR‐657	17q25.3	Upregulated	N = 94 48 GDM 46 NGT	Human	THP‐1 cells	IL‐37	Enhances the proliferation of mononuclear macrophages and promotes the generation of inflammatory cytokines via IL-37/NF-κB signaling axis
Peng 2019^Citation31	miR-137	1p21.3	Upregulated in A2GDM	N = 39 9 A1GDM 11 A2GDM 20 NGT	Human	HTR-8/SVneo cells	FNDC5	Trophoblast dysfunction (↓viability and migration)
Qi 2019^Citation71	miR-185	22q11.21	Downregulated	N = 256 156 GDM 100 NGT	Human	–	–	–
Zhou 2019^Citation72	miR-132	17p13.3	Downregulated	N = 158 108 GDM 50 NGT	Human	HTR-8/SVneo cells	–	Protective role against GDM by enhancing the trophoblast cell proliferation
Zhao 2019^Citation86	miR-221	Xp11.3	Downregulated	N = 40 20 GDM 20 NGT	Rats	INS-1 cells	PAK1	Protects GDM-induced islet dysfunction by regulating proliferation, apoptosis and insulin secretion in islet βcells
Qiu 2020^Citation34	miR-518d	19q13.42	Upregulated	N = 120 60 GDM 60 NGT (40 mice 30 GDM 10 NG)	Human Mice	HTR8/SVneo cell	PPAR-α	Triggers inflammatory response via NF-κB Pathway
Zhao 2020^Citation29	miR-140	16q22.1	Upregulated	N = 53 33 GDM 20 NGT	Human	HTR-8/SVneo, HEK293 cells and HUVEC cells	IR-α, IGF1R	Involved in the defective placental IR signaling in patients with GDM
Guan 2020^Citation35	miR-21	17q23.1	Downregulated	N = 295 137 GDM 158 NGT	Human	HTR-8/SVneo cells	PPAR-α	Trophoblast dysfunction (↑ cell proliferation, migration and invasion; ↓ apoptosis)
Zhang 2020^Citation56	miR-222	Xp11.3	Upregulated	N = 226 113 GDM 113 NGT (72 GDM mice)	Human, Mice	HEK-293T cells	CXCR4	Role in inflammatory response in GDM mice
Sun 2020^Citation77	miR-29b	7q32.3	Downregulated	N = 406 204 GDM 202NGT	Human	HTR-8/SVneo cells	HIF3A	Trophoblast dysfunction (↓cell proliferation, migration, and invasion; ↑apoptosis)
Song 2021^Citation30	miR-9 miR-22	17p13.3	Downregulated Downregulated	N = 51 31 GDM 20 NGT	Human	HTR8/SVneo cells, HEK293T cells and primary syncytiotrophoblasts	GlUT1, HK2 GLUT1	Increases glucose uptake, lactate secretion, and cell viability and represses apoptosis
Li 2021^Citation19	miR-345-3p	14q32.2	Downregulated	N = 60 30 GDM 30 NGT	Human	HTR-8/SVneo cells	BAK1	Trophoblast dysfunction (↑ cell proliferation, migration, and invasion; ↓ apoptosis)
Zhang 2021^Citation73	miR-125b miR-144	11q24.1 17q11.2	Downregulated Upregulated	N = 79 39 GDM 40 NGT	Human	–	–	–
Zhang 2021^Citation20	miR-30d-5p	8q24.22	Downregulated	N = 362 166 GDM 196 NGT	Human	HTR8 cells	RAB8A	Trophoblast dysfunction (↓cell proliferation, migration, and invasion; ↑ apoptosis) Downregulation of miR-30d-5p promotes glucose uptake in trophoblasts.
Zhang 2021^Citation78	miR-362-5p	Xp11.23	Downregulated	N = 80 40 GDM 40 NGT	Human	HTR-8/SVneo cells	GSR	Trophoblast dysfunction (↑cell proliferation; ↓apoptosis)
Yu 2021^Citation74	miR-96-5p	7q32.2	Downregulated	N = 246 123 GDM 123 NGT	Human	HTR-8/SVneo cells	–	Alleviates reduced viability of trophoblasts induced by high glucose

Notes: ↑Indicates a promotive effect; ↓Indicates an inhibitory effect.

Abbreviations: GDM, gestational diabetes mellitus; NGT, normal glucose tolerance; A1GDM, GDM patients treated with lifestyle-intervention; A2GDM, GDM patients treated with medication; miR, microRNA.

Figure 1 Effects of aberrantly expressed ncRNAs on trophoblast cells in GDM.

Notes: Green arrows indicate ncRNA knockdown. Orange arrows indicate ncRNA overexpression. Different from miRNAs, circRNAs and lncRNAs are in bold italics and bold, respectively. Black arrows indicate a promotive effect on trophoblast function. Black T-bars indicate an inhibitory effect on trophoblast function.
Abbreviations: GDM, gestational diabetes mellitus; ncRNA, non-coding RNA; miR, microRNA; MEG3, maternally expressed gene 3; PVT1, plasmacytoma variant translocation 1; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; circ_0005243, hsa_circ_0005243 (a circular RNA).

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