Table 3.

Effects of lncRNAs in acute myeloid leukemia

lncRNA	Expression	Effects	Does the lncRNA promote or demote AML formation?	Can it be used as a biomarker or prognostic tool?	References
H19	Upregulated	H19 upregulation shows that it behaves as a proto-oncogene in several AML cases, however it has also been observed to be downregulated and causes apoptosis in several other AML/CML cases through the H19/IGF2 axis. This differing characteristic can be attributed to the small sample size of observations.	It has oncogenic properties in several AML cases when upregulated, but can also have tumor suppressing roles in certain AML cases. Its effect differs with the sex and age of the patient as well.	Unmethylated H19 can be used as a prognostic biomarker. H19/ID2 has a therapeutic target value.	[81,82]
HOTAIR	Upregulated	It regulates LSC self-renewal by sponging miR-193a and by modulating c-KIT expression.	Its expression increases the pathogenicity of AML.	High HOTAIR expression is correlated with poor prognosis in AML patients.	[89-93]
UCA1	Upregulated	It results in increased AML cell viability, growth, metastasis and cell invasion. This lncRNA binds with miR-126 and downregulates its action. However, overexpressed miR-126 binds to 3’UTR of RAC1 and inhibits its action. The PI3/AKT and JAK/STAT pathway is also blocked by miR-126 overexpression. Hence the PI3/AKT pathways are activated by lncRNA UCA1. UCA1 also sponges miR-125a and miR-16.	Its expression aids in AML formation.	Could be used as a therapeutic target as it is abundant in patients with CEBPA mutation.	[94-96]
CRNDE	Upregulated	It is found to be overexpressed in AML cells and it results in inhibition of apoptosis, increased proliferation, and increased cloning.	It increases AML pathogenicity.	Its presence is a measure of poor prognosis. Can be used as a therapeutic target. It is seen to be overexpressed in M4 and M5 type of FAB cells, as compared to M1, M2 and M3 cells.	[97]
PVT1	Upregulated	It is elevated in t(8;21) AML and APL cases. It sponges miR-1204. It regulates MYC activation which is necessary for maintaining oncogenic state. PVT1 knockdown results in reduced cell migration and proliferation.	It increases AML pathogenicity.	Its expression is a measure of poor prognosis.	[84-87]
PANDAR	Upregulated	It results in AML pathogenesis by inhibiting the proapoptotic gene expression. This is done by interacting with the NF-YA transcription factor. It also results in higher BM (bone marrow) blast count and lower CR (complete remission) rate. The overall survival of the patients is also found to be shortened.	It results in AML pathogenesis.	It is used as a biomarker and as a prognostic marker. High expression levels result in poor prognosis especially in older individuals.	[98,99]
RUNXOR	Upregulated	It is involved in chromosomal translocation by interacting with the RUNX1 promoter via its 3’-terminal fragment. This results in the formation of an intrachromosomal loop. Mostly seen in t(8;21) AML cases. It also interacts with EZH2 which is a H3K27 methylase.	It results in AML proliferation.	Could play therapeutic and prognostic role.	[88]
CCAT1	Upregulated	Promotes HL-60 cell growth by inhibiting miR-155 which has tumor suppressive properties. Hence, AML patients have less amounts of miR-155. This results in repressed monocytic differentiation, and promotes cell growth. CCAT1 upregulation is found in mainly M4 and M5 AML patients according to the FAB system.	Promotes AML cell growth by sequestering miR-155.	Its expression is a measure of poor prognosis. Downregulating CCAT1 can serve as a therapeutic target.	[84,100]
TUG1	Upregulated	TUG1 suppresses miR-34a by recruiting EZH2, this results in ADR resistance. It also induces cell proliferation and inhibits AML cell apoptosis by targeting the aurora kinase A (AURKA).	Promotes AML proliferation.	High expression of TUG1 results in poor prognosis.	[101,102]
CCDC26	Upregulated	It is also known as retinoid modification (RAM) and is associated with pediatric AML. It is involved with the regulation of the differentiation and apoptosis of acute monocytic leukemia cell lines via regulating c-KIT expression.	Increases AML proliferation.	High expression is a measure of poor prognosis.	[103,104]
MONC	Upregulated	Enhances the proliferation of immature erythroid progenitor cells.	Increases AML proliferation.	Could play therapeutic role.	[105]
MIR100HG	Upregulated	Involved in AML cell proliferation, viability, and colony formation.	Increases AML proliferation.	Could play therapeutic role.	[105]
HOXA-AS2	Upregulated	Through a TRAIL mediated pathway, HOXA-AS2 suppresses apoptosis that is induced by ATRA. However, this HAOX-AS2 is also induced by ATRA. Net result is increase in the number of viable cells, and decrease in apoptosis.	Increases AML proliferation.	HOXA-AS2 is therapeutic targets need to be identified.	[106,107]
MALAT	Upregulated	Sponges and downregulates miR-96. It increases AML cell proliferation, and decreases apoptosis. It’s knockdown results in increased cytarabine (Ara-C) chemosensitivity by upregulating miR-96.	Increases AML proliferation.	Results in poor prognosis.	[108,109]
MEG3	Downregulated	In a p53 dependent manner, MEG3 is seen to inhibit tumorigenesis. However, its methylation is seen to increase tumor formation and results in poor prognosis. MEG3 can also inhibit tumorigenesis in a p53 independent manner as well. Ten-eleven translocation 2 (TET2) is seen to upregulate MEG3 expression via a TET2-WT1-MEG3 axis, and this results in increased AML proliferation.	Decreases AML proliferation.	Methylation of MEG3 results in poor prognosis and reduced overall survival rates. Can be used as a biomarker.	[110,111]
CASC15	Upregulated	CASC15 is a tumor suppressor gene and it results in reduced colony formation. It also limits AML cell proliferation. It regulates the SOX4 gene by modulating the transcription factor YY1.	It suppresses AML proliferation.	Studies on CASC15 have given insights into using them as potential therapeutic agents.	[112]
IRAIN	Downregulated	It is involved in inhibition of tumor cell migration. It is found to be more expressed in low-risk AML patients, but less expressed in high-risk AML patients. It is closely linked with the IGF1 promoter sequence. Exposing the AML cells to cytarabine (AraC), which is a chemotherapeutic agent, results in enhancing IRAIN expression.	It suppresses AML proliferation.	Results in shorter overall survival and results in a refractory response to chemotherapy.	[113,114]
NEAT1	Downregulated in AML pathogenesis condition.	Results in suppressing AML cell proliferation and induces apoptosis. This is done via the NEAT1/miR-23a-3p/SMC1A axis. NEAT1 expression downregulates miR-23a-3p expression which leads to SMC1A upregulation, which then reverses AML proliferation.	It is generally downregulated in AML state, but inducing its upregulation results in decreasing AML proliferation.	Could be used as a therapeutic target by upregulating NEAT1 expression in AML affected cells.	[115]
LOC285758	Upregulated	LOC285758 increases AML pathogenesis by regulating HDAC2 expression. Knockdown of LOC285758 results in increased cell apoptosis and inhibits cell proliferation.	Increases AML proliferation.	Indicates poor prognosis in AML patients.	[116-118]