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Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review)

  • Authors:
    • Yipei Jing
    • Xiaoqi Li
    • Ye Guo
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China, Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, P.R. China
    Copyright: © Jing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 57
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    Published online on: November 28, 2025
       https://doi.org/10.3892/ol.2025.15410
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Abstract

A newly recognized class of master regulators known as long non‑coding RNAs (lncRNAs) has emerged as key modulators of cancer. Among them, HOXA transcript antisense RNA myeloid‑specific 1 (HOTAIRM1) was initially identified in acute promyelocytic leukemia, where it resides within the HOXA gene cluster. The involvement of HOTAIRM1 has been indicated in the pathogenesis of multiple cancer types, including glioma, acute myeloid leukemia and osteosarcoma, has been well documented. HOTAIRM1 controls the growth, invasion and migration of tumors through different mechanisms and it is associated with the clinicopathological characteristics of patients with tumors. The present review describes the expression, function and molecular mechanism of HOTAIRM1 in different types of cancer and discusses the future obstacles in diagnosing and treating malignant tumors.
View Figures

Figure 1

Schematic diagram of HOTAIRM1.
HOTAIRM1, a long non-coding RNA located between HOXA1 and HOXA2, on
the human chromosome 7p15.2. Arrows indicate transcription
direction: Black for HOXA genes; red for the HOTAIRM1 transcript.
HOTAIRM1, HOXA transcript antisense RNA myeloid-specific 1; chr,
chromosome; HOX, homeobox.

Figure 2

HOTAIRM1 interaction with DNA to
exert a regulatory role in tumor progression. Interaction with
PRC2/EZH2: HOTAIRM1 directly interacts with EZH2 of the PRC2
complex, preventing the deposition of the repressive H3K27me3 mark
at target gene promoters; Interaction with H3K9 methyltransferases
and DNMTs: HOTAIRM1 binds to and prevents the recruitment of H3K9
methyltransferases and DNA methyltransferases to promoters, thereby
reducing repressive H3K9me2 and DNA methylation. Interaction with
histone demethylases: HOTAIRM1 interacts with histone demethylases
to help control chromatin structure and activate transcription of
target gene cluster. HOTAIRM1, HOXA transcript antisense RNA
myeloid-specific 1; EZH2, enhancer of zeste homolog 2; H3K27me3,
lysine residue 27 of histone 3; H3K9me2, histone H3 lysine 9
dimethylation; UTX, ubiquitously transcribed tetratricopeptide
repeat on chromosome X; MLL, mixed lineage leukemia; PRC2, polycomb
repressive complex 2; G9a, euchromatic histone-lysine
N-methyltransferase 2.

Figure 3

HOTAIRM1 interaction with RNA to
exert a regulatory role in tumor progression. Interaction with
specific miRNAs (e.g., miR-152-3p, miR-664b-3p, miR-29b-1-5p,
miR-519a-3p): HOTAIRM1 functions as a competitive endogenous RNA or
‘molecular sponge’ by binding to these miRNAs, leading to the
upregulation of genes like ULK3, ETS1, Rheb, PHLPP1, Bax, and
Bcl-2, which in turn modulates tumor progression. Interaction with
IGFBP2 mRNA: HOTAIRM1 directly binds to IGFBP2 mRNA to promote
tumor progression. HOTAIRM1, HOXA transcript antisense RNA
myeloid-specific 1; miR, microRNA; ULK3, Unc-51 like kinase 3;
ETS1, E26 transformation-specific 1; Rheb, Ras homolog enriched in
brain; PHLPP1, PH domain leucine-rich repeat protein phosphatase 1;
IGFBP2, insulin-like growth factor binding protein 2.

Figure 4

HOTAIRM1 interaction with proteins to
exert a regulatory role in tumor progression. Interaction with
HSPA5: HOTAIRM1 interacts with HSPA5 to transcriptionally regulate
its expression, influencing tumor progression. Interaction with
PTBP1 and IGF2BP2: HOTAIRM1 forms a complex with PTBP1 and IGF2BP2
to enhance its stability, thereby promoting tumor progression.
Interaction with FUS: HOTAIRM1 binds to the RNA-binding protein FUS
to promote tumor progression. Interaction with HOXA1: HOTAIRM1
interacts with HOXA1 to regulate tumor progression. Interaction
with EGR1: HOTAIRM1 acts as a scaffold, facilitating the EGR1 to
promote tumor progression. HOTAIRM1, HOXA transcript antisense RNA
myeloid-specific 1; IGF2BP2, insulin-like growth factor 2
mRNA-binding protein 2; EGR1, early growth response 1; FUS, fused
in sarcoma; HSPA2, heat shock protein family A (Hsp70) member 2;
PTBP1, polypyrimidine tract-binding protein 1; HOXA1, homeobox
A1.

Figure 5

HOTAIRM1 regulates various hallmarks
of cancer. HOTAIRM1 promotes cell proliferation by upregulating
Igfbp2/Hspa5/mTor or downregulating Egr1, while also upregulating
Pik3cd to exert an inhibitory effect on proliferation; HOTAIRM1
suppresses apoptosis by downregulating Bcl-2/Bid/p53 and promotes
autophagy by upregulating Ulk3/LC3 while downregulating p62;
HOTAIRM1 promotes EMT by upregulating Hoxa1 and downregulating
BTG3, leading to increased N-cadherin/Vimentin/Snail and decreased
E-cadherin; HOTAIRM1 promotes cell differentiation by upregulating
Nanog/Sox2/Pou5f1/Ets1 and downregulating miR-125b; HOTAIRM1
promotes metabolic reprogramming by upregulating mTOR/Hk2 to
enhance glycolysis and increasing Shmt2 to stimulate serine
metabolism; HOTAIRM1 modulates therapy response through
upregulating RhoA/ROCK1/Beclin-1/BTG3 expression. HOTAIRM1, HOXA
transcript antisense RNA myeloid-specific 1; Igfbp2, insulin-like
growth factor binding protein 2; Egr1, early growth response 1;
miR, microRNA; Ulk3, Unc-51 like kinase 3; Hoxa1, homeobox A1;
Ets1, E26 transformation-specific 1; Shmt2, serine
hydroxymethyltransferase 2; Hk2, hexokinase 2; Btg3, B-cell
translocation gene 3; Rock1, ρ-associated coiled-coil containing
protein kinase 1; Rhoa, Ras homolog family member A; Bid, BH3
interacting-domain death agonist; Pik3cd,
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit
∆.
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Copy and paste a formatted citation
Spandidos Publications style
Jing Y, Li X and Guo Y: Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review). Oncol Lett 31: 57, 2026.
APA
Jing, Y., Li, X., & Guo, Y. (2026). Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review). Oncology Letters, 31, 57. https://doi.org/10.3892/ol.2025.15410
MLA
Jing, Y., Li, X., Guo, Y."Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review)". Oncology Letters 31.2 (2026): 57.
Chicago
Jing, Y., Li, X., Guo, Y."Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review)". Oncology Letters 31, no. 2 (2026): 57. https://doi.org/10.3892/ol.2025.15410
Copy and paste a formatted citation
x
Spandidos Publications style
Jing Y, Li X and Guo Y: Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review). Oncol Lett 31: 57, 2026.
APA
Jing, Y., Li, X., & Guo, Y. (2026). Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review). Oncology Letters, 31, 57. https://doi.org/10.3892/ol.2025.15410
MLA
Jing, Y., Li, X., Guo, Y."Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review)". Oncology Letters 31.2 (2026): 57.
Chicago
Jing, Y., Li, X., Guo, Y."Role of HOXA transcript antisense RNA myeloid‑specific 1 in cancer (Review)". Oncology Letters 31, no. 2 (2026): 57. https://doi.org/10.3892/ol.2025.15410
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