Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment

Mafi, Alireza; Rahmati, Atefe; Babaei Aghdam, Zahra; Salami, Raziyeh; Salami, Marziyeh; Vakili, Omid; Aghadavod, Esmat

doi:10.1186/s11658-022-00354-4

Cellular & Molecular Biology Letters

Table 1 MicroRNAs involved in the pathogenesis of glioma

From: Recent insights into the microRNA-dependent modulation of gliomas from pathogenesis to diagnosis and treatment

miRNA	Expression pattern	Study model	Sample type	Malignant behavior	Target(s)	Ref.
miR-21	Upregulated	In vitro In vivo	U87 glioma cell lines Xenograft tumor	Inhibition of apoptosis	Destabilizing TNFRs and decreasing the molecules involved in apoptosis including caspase-3, caspase-9, and APAF1	[93]
miR-221/222	Upregulated	In vitro In vivo	U251 glioblastoma/rat C6 glioma cells Xenograft tumor model (U251 glioma)	Induce proliferation of cell and disrupt cell death	Cell cycle inhibitors including p27 and/or p57	[96]
miR-34a	Downregulated	In vitro	MSCs-U87 U87-MG glioblastoma	Inhibition of glioma cell growth and cell cycle progression	Direct inhibition of expression of various cellular factors such as c-MET RTK, Notch-1, Notch-2, CDK6, CCND1, and SIRT1	[99, 100]
miR-124-3p	Downregulated	Human In vitro	Tissue samples U251 and U87 glioma cell lines/SHG44 glioblastoma cell line	Disrupt glioma cell proliferation, invasion, and migration	Connection with a variety of extracellular receptors such as NRP-1	[106, 107]
miR-125b	Upregulated	In vitro	U343 and U251 glioma cells	Induction of glioma cell proliferation, as well as inhibiting ATRA-induced cell apoptosis	Interaction with the 3′-UTR of Bmf	[108]
miR-9	Downregulated	Human In vitro	Tissue samples U87 MG (CL-0238) and TG-905 (CL-0309) glioblastoma cell lines	Inhibition of glioma cells proliferation and increased apoptosis	FOXG1 signaling	[122]
miR-186	Downregulated	Human In vitro	Tissue samples U87 glioma/astrocyte HA1800 cell lines	Increasing apoptosis	Inhibition of Smad6	[123]
miR-142-3p	Downregulated	Human In vitro	Tissue samples U251 and U87 cell lines	Inhibition of glioma cells proliferation and mitigates apoptosis	Inactivated Wnt/β-catenin signaling and activated caspase-3 signaling by targeting HMGB1	[124]
miR-25	Upregulated	Human In vitro	Tissue samples U-373MG Uppsala, U-87MG Uppsala, U251MG, and T98G glioma cell lines	Induction of tumor cell migration, invasiveness, and proliferation	Increasing expression of CADM2	[133]
miR-146b-5p	Downregulated	Human In vitro	Tissue samples U87MG/SNB19 cell lines	Inhibition of glioma cells migration and invasion	Degradation of MMP16-related mRNA	[139]
miR-379-5p	Downregulated	In vitro	U87 and U251 glioma cell lines/human astrocyte normal cells/HEB cells	Inhibition of glioma cells viability, migration, invasion, and EMT	Modulation of MGST1	[140]
miR-665	Downregulated	Human In vitro	Tissue samples U251MG, A172, LN18, and T98G glioma cell lines	Inhibition of glioma cell proliferation, migration, and invasion	Targeting HMGB1, as well as inhibiting the Wnt/β-catenin pathway	[143]
miR-3175 miR-134	Upregulated Downregulated	Human In vitro	Tissue samples U251 glioma cells	Affecting cell proliferation and apoptosis, as well as EMT	PI3K/Akt pathway	[148, 149]
miR-296	Downregulated	Human In vitro	Tissue samples U251 glioma cell line	Inhibition of cell invasion and multidrug resistance	Particular types of potassium channels such as EAG1 (also called KCNH1)	[150]
miR-320a	Downregulated	Human In vitro	Tissue samples U87 and U251 human glioma cell lines	Impeding invasion and migration of glioma cells	Aquaporin 4	[151]
miR-125b	Downregulated	Human In vitro	Pediatric low-grade glioma-derived cell lines (Res186, Res259, and BT66)	A decrease in cell growth and induction of apoptosis	The mechanisms is not clear	[155]
miR-125b	Downregulated	In vitro	Human brain microvascular endothelial cells	Inhibition of tumor angiogenesis	Molecular loop, which interacts with MAZ, VEGF, and miR-125b	[155]
miR-210-3P	Upregulated	In vitro	U87-MG, A172, and HS683 glioma cell lines	Induction of invasiveness and EMT in glioma cells Probable involvement in regulation of mitochondrial function	Modification of the mitochondrial membrane potential to improve mitochondrial function	[102]
miR-93	Upregulated	Human	Tissue samples	Induction of proliferation, cell cycle progression, colony formation, migration, invasion, and chemoresistance in glioma cells	Integrin β8	[158]
miR-124-3p	Downregulated	Human In vitro	Tissue samples U87MG and U251MG cell lines	Inhibition of the proliferation, invasion, and migration of glioma cells	Activating the PI3K/Akt/NF-κB signaling pathway	[152]
miR-21	Upregulated	In vitro	U87MG glioma cell line	Inhibition of TMZ-induced apoptosis	Decreasing the Bax/Bcl-2 ratio and caspase-3 activity	[167]
miR-125b-2	Upregulated	Human In vitro	Primary culture of glioblastoma tissues-derived cells	Induction of resistance of human glioblastoma stem cells to TMZ	Mitochondrial pathway of apoptosis	[169]
miR-128 and miR-149	Downregulated	Human In vitro	Tissue samples U251 and U87 glioma cell line	Inhibition of invasion of glioblastoma cells Increasing the TMZ sensitivity of glioblastoma cells	Rap1B-mediated cytoskeletal and related molecular alterations	[171]
miR-181a/b/c/d	Downregulated	Human In vitro	Tissue samples U251 and U87 glioma cell line	Increasing the TMZ sensitivity of glioblastoma cells Inhibition of invasive proliferation of glioblastoma cells	Rap1B-mediated cytoskeleton remodeling and related molecular (Cdc42, RhoA, and N-cadherin) changes	[172]
miR-155-3p	Upregulated	Human In vitro In vivo	Tissue samples LN299, A172, T98, U87, and U251 glioma cell lines and healthy human astrocytes Xenograft mice model (U87)	Induction of cell growth, while its inhibition promotes TMZ sensitivity Induction of cell arrest at the same point that TMZ acts on G1/S phase	Upmodulation of Six1 at translational level	[175]
miR-141-3p	Upregulated	Human In vitro In vivo	Tissue samples A172, U87, U251, T98, and LN229 glioma cell lines Xenograft mice model (U87)	Induction of cell growth and drug resistance Induction of tumor growth, as well as inhibition of cell apoptosis and cell cycle arrest	Suppression of p53 and its downstream proteins such as CDK2 and cyclin E1/B1, thus inhibiting cell cycle arrest at G1 to S phases	[176]
miR-195	Downregulated	In vitro	U251MG glioma cell line	Inhibition of miR-195-induced TMZ resistance and suppression of cell apoptosis of glioma cells	CCNE1	[177]
miR-524-5p miR-324-5p	Downregulated	Human In vitro In vivo	Profiling upon 158 glioma samples U87 and U251 glioma cells Xenograft mice model (U87)	Upregulation of miR-524-5p and miR-324-5p reduces glioma cell proliferation, but increases TMZ sensitivity	EZH2	[180]
miR-137	Downregulated	Human	Tissue samples	Inhibition of GSC self-renewal, while promoting their differentiation	Targeting RTVP-1, which downregulates CXCR4	[188]
miR-26a	Upregulated	In vitro In vivo	U251, U87, A172, and SHG44 glioma cell lines, human cervical cancer cell line HeLa, human embryonic kidney 293 and 293 T cells Xenograft mice model (U87)	Decreasing AP-2α expression by binding to the 3′-UTR of AP-2α and reversed the tumor-suppressive role of AP-2α in glioma	AP-2α/Nanog signaling axis	[192]
miR-30a	Downregulated	Human In vitro In vivo	Tissue samples A172, U87, and U251 glioma cell lines Xenograft mice model	Suppression of self-renewal and tumorigenicity of GSCs Exerting some antitumor effects on GSCs	Blocking the NT5E-dependent Akt signaling pathway	[194]
miR-30c	–	In vitro	Rat C6 glioma cell line	C6 cell sphere formation and neural differentiation to astrocytes	JAK–STAT signaling pathway	[195]
miR-33a	Upregulated	Human In vivo	Tissue samples Xenograft mice model	Increasing the PDE8A and UVRAG mRNAs’ expression	Modulation of PKA and Notch endocytosis signaling pathways	[196]
miR-300	Upregulated	Human In vivo	Tissue samples Xenograft mice model	Increasing the cell proliferation and self-renewal-related activities in patient-derived GSCs	Direct suppression of LZTS2	[239]
miR-29a	Downregulated	Human In vitro In vivo	Tissue samples U87 and U251 glioma cell lines BALB/c nude mice	Suppression of proliferation, migration, and invasion, but promotion of glioma cell apoptosis	Aberrated expression of MDM2/4 and final deregulation of the activity of the p53-miR-29a-MDM2/4 feedback loop	[173]

Akt protein kinase B; APAF1 apoptotic protease activating factor 1; ATRA all-trans retinoic acid; Bax Bcl-2-associated X; Bcl-2 B cell lymphoma protein -2; Bmf Bcl-2 modifying factor; CADM2 cell adhesion molecule 2; CCND1 Cyclin D1; Cdc42 cell division cycle 42; CDK cyclin-dependent kinase; CXCR4 C-X-C chemokine receptor type 4; EAG1 Ether-à-go-go1 potassium channel; EMT epithelial–mesenchymal transition; EZH2 Enhancer of zeste 2 polycomb repressive complex 2 subunit; FOXG1 Forkhead box G1; HMGB1 high mobility group box 1; KCNH1 potassium voltage-gated channel subfamily H member 1; LZTS2 leucine-zipper tumor suppressor 2; MAZ MYC associated zinc finger protein; MDM2 mouse double minute 2; MGST1 microsomal glutathione S-transferase 1; MMP16 matrix metalloproteinase 16; MSCs mesenchymal stem cells; NF-κB nuclear factor-κB; NRP neuropilin; NT5E 5′-nucleotidase ecto; PDE8A phosphodiesterase 8A; PI3K phosphoinositide 3-kinase; Rap1B Ras-associated protein 1B; RhoA Ras homolog family member A; RTK receptor tyrosine kinase; SIRT1 Sirtuin1; Six1 sine oculis homeobox 1; TMZ temozolomide; TNFRs tumor necrosis factor receptors; UTR untranslated region; UVRAG UV radiation resistance-associated gene; VEGF vascular endothelial growth factor

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ISSN: 1689-1392

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