Table 3.

Target genes of prominent microRNAs in lymphoid malignancies and their role in regulating GC-mediated apoptosis. Relations to GC signaling and/or GC-induced apoptosis are highlighten in bold. More detailed description is found in Sections 3 and 4.

miRNA	Important target genes	Regulation/expression	Effect on GC-induced apoptosis	References
let-7 family	K-Ras, Myc, HMGA2, PLCγ1, IMP-1, Dicer, IL-6, E2F2, CCND (Cyclin D2, Cdc25A, CDK6, Bcl- X L, PRDM1/Blimp1	↓ CLL ↓ MM ↓ T-ALL ↓ BL ↓Myc	Anticipated to synergize with GC	[345, 361, 473, 476–479, 525, 564, 640]
miR-9	PRDM1/Blimp1 NFκB	↑ FL		[564, 640–642]
miR-15a~16	Bcl-2, CHEK1, CCND1 (Cyclin D1), CCND2 (Cyclin D2), CCND3 (Cyclin D3), CCNE (Cyclin E), CDK4, CDK6, Wnt3a, E2F, Cdc25A, Mcm5	↑↓ CLL ↓ MM ↑GC ↑E2F1-3 ↓c-Myc	Promote GC-induced apoptosis	[255, 345, 346, 471, 473, 515, 525, 564, 566, 576, 643–646]
miR-17~92 cluster	Bim (Bcl2L11),   PTEN, E2F1, Notch1, Hoxa9, CYLD, RUNX1, p21	↑ T-ALL ↑ CLL ↑ MM ↑ BCL ↑ ALK+-ALCL ↑ DLBCL ↑ BL ↓GC ↑ c-Myc ↑ E2F1 ↓ GSI	Attenuates GC-induced apoptosis. Considered as an OncomiR.	[135, 206, 246–248, 255, 445, 467, 469, 515, 525, 564, 574, 618, 647, 648]
miR-18 (member of the miR-17~92 cluster)	GR		Reduced GR-mediated transactivation	[649]
miR-21	PTEN, PDCD4, TPM-1, Tap63, SPRY2, Msh2, SHIP1, TRAIL-3	↑ CLL ↑ CML ↑ MM ↑ BCL ↑ DLBCL ↓FoxO3a	Expected to prevent GC-induced apoptosis, due to increased Akt signaling. Considered as an OncomiR.	[268, 269, 525, 566, 574, 579, 580, 650–654]
miR-23a/b	Notch1, PLK3, PAX, MTSS1	↑ CLL ↓ cHL ↓ Relapsed T-ALL		[590, 655, 656]
miR-26a	PTEN, Bim, EZH2, c-Myc, CCND3 (Cyclin D3), CCNE2 (Cyclin E2)	↑ T-ALL ↑ CLL ↓ BL ↓ Myc	Expected to prevent GC-induced apoptosis. Considered as an OncomiR.	[253, 315, 465, 473, 481, 565, 566, 629]
miR-27a	Fbw7, ZBTB10, Myt-1, MDR, BMI1, FoxO1/3	↑ B-ALL ↓ DLBCL ↓GSI ↓GC		[253, 258, 438, 439, 445, 446, 657, 658]
miR-29a/b	Mcl-1, Tcl-1, CDK6, PTEN, DNMT1, DNMT3A, DNMT3B p85α, CDC42	↓ ALCL ↓ CLL ↓ MM ↓ MCL ↓ DLBCL ↓ BL ↓ Myc ↓ NFκB	Expected to synergize with GC.	[316, 380–383, 473, 564–566, 569, 574, 583, 587, 643, 655, 659–662]
miR-34a/b/c	Bcl-2, E2F1, c-Myb, B-Myb SIRT1, ZAP70, Notch1,   Delta1,   Jagged1	↑↓ CLL ↑p53 ↑PMA ↓Myc		[347, 348, 443, 473, 570, 663–667]
miR-101	mTOR, Mcl-1, Cox2, Fos, EZH2	↓ ALCL	Expected to synergize with GC.	[384, 587]
miR-106a~363 and miR-106b~25	p21/CDKN1a Bim, PTEN	↑ MCL ↑ MM ↑ DLBCL ↓GC	Attenuates GC-induced apoptosis	[254–256, 314, 574, 591, 668, 669]
miR-124a	GR	↑ MCL ↓ ALL	Reduced GR-mediated transactivation	[560, 583, 649, 670]
	CDK6 Hes-1
miR125a	PDPN, Bak1, KLF13, preproET1, ARID3B, HuR, ERBB2, ERBB3			[576]
miR-125b	IRF4 PRDM1-Blimp1 Lin28, STAT3 Bak1, Bmf   Mcl-1, Bcl-w, Bcl-2	↓ CLL	It has both pro- and anti-apoptotic effect.	[349–352, 356, 533, 571, 595, 671]
miR-128b	BMI1	↓ Relapsed T-ALL ↓ MLL-AF4-ALL ↓GC	miR-128 sensitizes MLL-AF4 ALL to GC.	[646, 655, 672, 673]
miR-130b	GR	↑ DLBCL ↑ Relapsed T-ALL	Attenuates GC-induced apoptosis.	[655, 674–676]
	RUNX3 p21
miR-135a/b	JAK2,	↓ cHL		[590, 677]
miR-142	GR	↓ MCL ↑ T-ALL ↓GC	Confers GC resistance	[583, 657, 678–680]
	AC9
miR-143 and miR145	MLL-ALL ERK5	↓ CLL		[525, 573]
miR-146a	TRAF6, IRAK1, Fas, Smad4, TBP, CCL8-MCP-2	↑ MM ↑ T-ALL ↑ CLL ↓ BL ↓Myc		[473, 564, 576, 635, 637, 638, 681]
miR-150	c-Myb, DKC1 AKT2, Notch3	↑↓ CLL ↑ T-ALL ↓ MCL ↓ cHL ↓ DLBCL ↑GC ↓ Myc		[441, 473, 547, 565, 566, 583, 589, 682–684]
miR-155	SOCS1, ETS1, c-MAF, HGAL, FoxO3a, SHIP1, SMAD5, PU.1, C/EBPβ, CSFR, KPC1, CEBPB, IL-13Rα1, CUTL1, CYR61, SMAD1, ETS1, SMAD2,	↓↑ CLL ↑ DLBCL ↑ C-ALCL ↑ ALK−-ALCL ↑ MCL ↑ cHL ↑ NHL	Expected to prevent GC-induced apoptosis. Considered as an OncomiR.	[263, 264, 515, 525, 564, 566, 568, 576, 583, 584, 587, 589, 599, 602, 681, 685–691]
	MEIS1, RUNX2, MYO10, PKIα, JARID2, AGTR1, PICALM, BACH1, ZIC3,	↑↓ BL ↓GC (in MΦ) ↑ NFκB ↑ TLR4 ↑ c-Myb ↑ EBV
miR-181a/b	Tcl1, Lin28, Bcl-2, Mcl-1, XIAP, CYLD, GR, CD69, TCR, Hoxa7, Hoxa9, Hoxa11, PBX3, NLK, TIMP3, Prox1, DUSP5, DUSP6, SHP-2, PTPN22, FoxP1, p27Kip1	↓↑ CLL ↓↑ DLBCL ↑ MM ↑ T-ALL ↓  GC ↓  GSI	Dual role on GC-induced apoptosis: attenuation through repression of GR, but sensitization due to reduced expression of anti-apoptotic proteins.	[270, 358, 359, 385, 445, 539, 546, 549, 551, 552, 565, 568, 569, 574–576, 684, 692–694]
miR-182	FoxO1/3,    Fbw7	↑ T-ALL cell lines resistant to GC ↓ CLL ↑ MCL	Confers GC resistance.	[253, 258–261, 564]
miR-221 and miR-222	p27Kip1, p57Kip2, PTEN, TIPM3, FoxO3a, c-Kit, Puma, Dicer, APAF-1, WTAP, Ets1, Bmf, Mdm2	↑ CLL ↑ DLBCL ↑ MM ↓ MLL-AF4 ALL ↓GSI	Dual effect on GC-induced apoptosis. Usually oncogenic with anti-apoptotic effect. In MLL-AF4 ALL, miR-221 sensitizes the cells to GC. Considered as an OncomiR.	[321, 445, 525, 533, 563, 575, 576, 580, 672, 695–699]
miR-223	LMO2, NFI-A, MYBL1, E2F1, Fbw7, Mef2c, IGFR	↓↑  T-ALL ↓ CLL ↓ DLBCL ↓ Relapsed T-ALL ↑  GC ↑ C/EBPα ↓ NFI-A ↓ E2F1	May sensitize to GC-induced apoptosis by preventing Akt activation.	[515, 533, 565, 566, 646, 655, 700–706]
miR-708	FoxO3	↑ Relapsed T-ALL	May confer GC resistance.	[655]

↑ upregulated, ↓ downregulated.

Abbreviations: AC9: adenylyl cyclase 9; BCL: B-cell lymphoma, Blimp1: B lymphocyte-induced maturity protein 1; cHL: classical Hodgkin's lymphoma; GSI- gamma secretase inhibitor; LMO2: LIM domain only 2; MDR: multidrug resistant gene; Msh2: DNA MutS homolog 2; MTSS1: Metastasis suppressor 1; NHL: non-Hodgkin's lymphoma; NLK: nemo-like kinase; PDCD4: programmed cell death 4; PMA: phorbol myristate acetate; SHIP1: SH2 (Src-homology 2) domain-containing inositol phosphatase 1; SOCS1: suppressor of cytokine signaling; SPRY2: Sprouty2; TPM-1: Tropomyosin 1; TRAF6: TNF receptor-associated factor 6; WTAP: Wilms' tumor-associated protein isoform 1; XIAP: X-linked inhibitor of apoptosis protein.