Open Access

HOTTIP suppresses ferroptosis via mediating DGCR8/miR‑214‑3p/GPX4 regulatory axis in osteosarcoma

  • Authors:
    • Shou-Chang Ding
    • Chuan-Jian Shi
    • Feng-Xiang Pang
    • Rui-Jia Wen
    • Nan Li
    • Yong-Xin Mai
    • Shu-Ting Zhou
    • Jin-Fang Zhang
  • View Affiliations

  • Published online on: June 13, 2025     https://doi.org/10.3892/or.2025.8927
  • Article Number: 94
  • Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents and the current typical strategy remains unsatisfactory in clinical practice. Ferroptosis has been considered as a novel form of programmed cell death in eukaryotic cells, which is characterized by iron‑dependent lipid peroxidation accumulation. The emergence of ferroptosis brings great hope to develop the potential therapeutic targets for OS patients. Long noncoding (lnc)RNA HOXA transcript at the distal tip (HOTTIP) has been identified as an oncogene to facilitate tumorigenesis in OS. Whether ferroptosis participates in this lncRNA mediated OS tumorigenesis is not fully understood. In the present study, HOTTIP was found to be downregulated in the Erastin‑treated OS cells. Silence of HOTTIP promoted, while ectopic expression of HOTTIP suppressed, ferroptosis in OS cells in vitro and in vivo. Mechanically, HOTTIP recruited the RNA binding protein DiGeorge Critical Region 8 (DGCR8) and influenced its protein stability, which disrupted miR‑214‑3p biogenesis and facilitated the de‑repression of glutathione peroxidase 4 transcription, eventually leading to preventing ferroptosis. Taken together, the present study demonstrated that HOTTIP suppressed ferroptosis in OS cells via DGCR8/micro RNA 214‑3p/GPX4 regulatory axis, which might provide insights to develop HOTTIP as a promising therapeutic target for OS patients.
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August-2025
Volume 54 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ding S, Shi C, Pang F, Wen R, Li N, Mai Y, Zhou S and Zhang J: HOTTIP suppresses ferroptosis via mediating DGCR8/miR‑214‑3p/GPX4 regulatory axis in osteosarcoma. Oncol Rep 54: 94, 2025.
APA
Ding, S., Shi, C., Pang, F., Wen, R., Li, N., Mai, Y. ... Zhang, J. (2025). HOTTIP suppresses ferroptosis via mediating DGCR8/miR‑214‑3p/GPX4 regulatory axis in osteosarcoma. Oncology Reports, 54, 94. https://doi.org/10.3892/or.2025.8927
MLA
Ding, S., Shi, C., Pang, F., Wen, R., Li, N., Mai, Y., Zhou, S., Zhang, J."HOTTIP suppresses ferroptosis via mediating DGCR8/miR‑214‑3p/GPX4 regulatory axis in osteosarcoma". Oncology Reports 54.2 (2025): 94.
Chicago
Ding, S., Shi, C., Pang, F., Wen, R., Li, N., Mai, Y., Zhou, S., Zhang, J."HOTTIP suppresses ferroptosis via mediating DGCR8/miR‑214‑3p/GPX4 regulatory axis in osteosarcoma". Oncology Reports 54, no. 2 (2025): 94. https://doi.org/10.3892/or.2025.8927