Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance

Bhat, Ajaz A.; Younes, Salma N.; Raza, Syed Shadab; Zarif, Lubna; Nisar, Sabah; Ahmed, Ikhlak; Mir, Rashid; Kumar, Sachin; Sharawat, Surender K.; Hashem, Sheema; Elfaki, Imadeldin; Kulinski, Michal; Kuttikrishnan, Shilpa; Prabhu, Kirti S.; Khan, Abdul Q.; Yadav, Santosh K.; El-Rifai, Wael; Zargar, Mohammad A.; Zayed, Hatem; Haris, Mohammad; Uddin, Shahab

doi:10.1186/s12943-020-01175-9

Molecular Cancer

Table 1 Roles of ncRNAs implicated in leukemia

From: Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance

Type of ncRNA	ncRNA	Type of leukemia	Expression in leukemia	Mechanism/target/pathway	References
miRNA	miR-194-5p	AML	Upregulated	inducing BCLAF1; BCL2-associated transcription factor 1 (BCLAF1)	[18]
miRNA	miR-103	AML	Upregulated	Blocking PI3K/AKT signal pathway by regulation of COP1	[19]
miRNA	miR-15a	CML-CP	Upregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-130b	CML-CP	Downregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-145	CML-CP	Upregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-16	CML-CP	Downregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-26a	CML-CP	Downregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-146a	CML-CP	Downregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-29c	CML-CP	Downregulated	Expression modulated by BCR–ABL is linked to CML progression and imatinib resistance	[20]
miRNA	miR-96	AML	Downregulated	Oncogene Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) knockdown inhibited proliferation, promoted apoptosis and enhanced Ara-C sensitivity in AML cells by upregulating miR-96	[21]
miRNA	miR-128b	ALL	Downregulated	downregulation of the MLL-AF4 chimeric fusion proteins MLL-AF4 and AF4-MLL that are generated by chromosomal translocation t(4;11)	[22]
miRNA	miR-34a	AML	Downregulated	TUG1 confers Adriamycin resistance in acute myeloid leukemia by epigenetically suppressing miR-34a expression via EZH2	[23, 24]
miRNA	miR-451a	CML	Downregulated	NR	[25]
miRNA	let-7b-5p	CML	Downregulated	NR	[25]
miRNA	hsa-miR-425	AML	Upregulated	Through calcium signaling pathway and natural killer cell mediated cytotoxicity.	[26]
miRNA	hsa-miR- 200c	AML	Downregulated	NR	[26, 27]
miRNA	hsa-mir-30a	CML	Downregulated	NR	[28]
miRNA	miRNA-155	ALL	Upregulated	NR	[29]
miRNA	miR-130a	CML	Downregulated	Functions as a tumor suppressor by inhibiting multiple anti-apoptosis proteins, including BCL-2, MCL-1 and XIAP.	[30]
miRNA	miR-125b	AML; ALL	Upregulated	microRNA125b promotes leukemia cell resistance to daunorubicin through inhibiting apoptosis	[31]
miRNA	miR-224	CML	Downregulated	miR-224, along with let-7i, regulate the proliferation and chemosensitivity of CML cells probably via targeting ST3GAL IV.	[32]
lncRNA	HOXA-AS2	AML	Upregulated	HOXA-AS2 negatively regulates the expression of miR-520c-3p in ADR cells. S100A4 was predicted as a downstream target of miR-520c-3p,	[33]
lncRNA	TUG1	AML	Upregulated	TUG1 confers Adriamycin resistance in acute myeloid leukemia by epigenetically suppressing miR-34a expression via EZH2	[23, 34]
lncRNA	RP11-342 M1.7	AML	Upregulated	Involved in neoplastic signaling pathways	[35]
lncRNA	CDCA4P3	AML	Upregulated	Involved in neoplastic signaling pathways	[35]
lncRNA	CES1P1	AML	Downregulated	Involved in neoplastic signaling pathways	[35]
lncRNA	AC008753.6	AML	Downregulated	Involved in neoplastic signaling pathways	[35]
lncRNA	RP11-573G6.10	AML	Downregulated	Involved in neoplastic signaling pathways	[35]
lncRNA	MEG3	CML	Downregulated	contributes to imatinib resistance through regulating miR-21	[36]
lncRNA	PANDAR	AML	Upregulated	NR	[37]
lncRNA	GAS5	AML	Upregulated	Via affecting hematopoietic reconstitution	[38]
lncRNA	UCA1	CML	Upregulated	UCA1acts as a ceRNA Against miR-16 in Chronic Myeloid Leukemia Cells	[39]
lncRNA	MALAT1	CML	Upregulated	MALAT1 promotes imatinib resistance of CML cells by targeting miR-328	[40]
lncRNA	UCA1	AML	Upregulated	knockdown of UCA1 plays a role in overcoming the chemoresistance of pediatric AML, by inhibiting glycolysis through regulating the miR-125a/HK2 pathway.	[41]
lncRNA	NONHSAT076891	APL	Upregulated	NR	[42]
lncRNA	CRNDE	AML	Upregulated	NR	[13]
lncRNA	LINC00899	AML	Upregulated	NR	[12]
lncRNA	HOTAIR	CML	Upregulated	Knockdown of HOTAIR expression downregulates MRP1 expression levels and reverses imatinib resistance via PI3K/Akt pathway.	[43]
lncRNA	IRAIN	AML	Downregulated	Interaction with chromatin DNA and involvement in the formation of an intrachromosomal promoter loop	[44]
lncRNA	CCDC26	AML	Upregulated	NR	[45]
lncRNA	KCNQ1OT1	AML	Upregulated	NR	[46]
lncRNA	NONHSAT027612.2	ALL	Upregulated	Through regulating immune response-associated pathways.	[47]
lncRNA	NONHSAT134556.2	ALL	Upregulated	Through regulating immune response-associated pathways.	[47]
lncRNA	LINP1	AML	Upregulated	Via HNF4alpha/AMPK/WNT5A signaling pathway	[48]
lncRNA	SNHG3	AML	Upregulated	SNHG3 elicits a growth-promoting function in AML via sponging miR-758-3p to regulate SRGN expression	[49]
lncRNA	LUNAR1	ALL	Downregulated	Proliferation of T cells	[50, 51]
lncRNA	T-ALL-R-LncR1	ALL	Upregulated	Regulate apoptosis by Par-4/THAP1 protein complex	[52]
lncRNA	HOTAIRM1	AML	Upregulated	Chromatin modification, myeloid differentiation	[53, 54]
lncRNA	PVT1	AML	Upregulated	Oncogene, induce proliferation and suppress Apoptosis	[55]
lncRNA	ANRIL	AML/ALL	Upregulated	Myeloblast proliferation	[56]
lncRNA	BGL3	CML	Upregulated	Apoptosis and DNA methylation	[57]
circRNA	f-circPR	AML	Upregulated	High proliferation, chemo resistance, Differential expression	[58]
circRNA	circ-PVT1	AML	Upregulated	Involved in the development of leukaemia (AML)	[59]
circRNA	circNPM1 75,001 (hsa_circ_0075001)	AML	Upregulated	NPM1/regulate myeloid differentiation though miR-181,	[60]
circRNA	circ-HIPK2	AML	Downregulated	Regulate differentiation though miR-124-3p	[61]
circRNA	circRNA-DLEU2	AML	Upregulated	Enhanced cell division, survival, and proliferation with suppressed apoptosis through miR-496/ PRKACB	[62]
circRNA	hsa_circ_0004277	AML	Downregulated	Act as prognostic factor for survival outcome in AML patients. Target multiple miRNAs and Genes miR-138-5p, miR-30c-1-3p, miR-892b, miR-571, miR-328-3p/SH3GL2, PPARGC1A, PIP4K2C, SH2B3, ZNF275, and ATP1B4	[63]
circRNA	circ-CBFB	CLL	Upregulated	regulating miR-607/FZD3/Wnt/beta-catenin pathway	[64]
circRNA	circ_0132266	CLL	Downregulated	circ_0132266 acts as a sponge of miR-337-3p and regulates its activity, resulting in a downstream change of target-gene PML, influencing cell viability.	[65]
circRNA	circPAN3	AML	Upregulated	circPAN3-miR-153-5p/miR-183-5p-XIAP axis; circPAN3 may facilitate AML drug resistance through regulating autophagy and influencing expression of apoptosis-related proteins	[66, 67]
circRNA	circ_0009910	AML	Upregulated	knockdown of circ_0009910 inhibited AML cell proliferation and induced apoptosis by acting as a sponge for miR-20a-5p	[68]
circRNA	circ_100053	CML	Upregulated	involved in imatinib resistance	[69]
circRNA	hsa_circ_0080145	CML	Upregulated	knockdown of hsa_circ_0080145 significantly suppressed CML cell proliferation thorugh acting as a sponge for miR-29b.	[70]
circRNA	circ-ANAPC7	AML	Upregulated	circ-ANAPC7 targets the MiR-181 Family	[71]
circRNA	hsa_circ_0004277	AML	Downregulated	Increasing level of hsa_circ_0004277 by chemotherapy was associated with successful AML treatment	[63]
circRNA	circBA9.3	CML	Upregulated	Chemoresistance, Oncogene, Induce cell proliferation and supressed apoptosis	[72]
siRNA	SKP2	AML	Upregulated	SKP2 inhibits the degradation of P27kip1 and down-regulates the expression of MRP	[73]

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