2. Academic Validation
  3. LncRNA OLMALINC promotes osteosarcoma progression through USP1-mediated autophagy suppression

LncRNA OLMALINC promotes osteosarcoma progression through USP1-mediated autophagy suppression

  • Hum Cell. 2025 Apr 18;38(3):91. doi: 10.1007/s13577-025-01221-y.
Jianping Li # 1,  Bo Yu # 2,  Zhaowen Xue # 2,  Yiping Liang 3,  Shanchuang Chen 4,  Tao Gui 4,  Zitao Liu 5,  Lei Zhang 6,  Rui Peng 7
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  • 2 Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
  • 3 Department of Basic Research Department, Guangzhou National Laboratory, Guangzhou, Guangdong, China.
  • 4 Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  • 5 Department of Orthopaedics, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. hcaepliu@gzucm.edu.cn.
  • 6 Department of General Surgery, The Second Affiliated Hospital of Bengbu Medical University, Bengbu, 233080, Anhui, China. leizhang@bbmu.edu.cn.
  • 7 Department of Bone and Joint Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. pengrui0912@jnu.edu.cn.
  • # Contributed equally.
PMID: 40249458 DOI: 10.1007/s13577-025-01221-y
Abstract

Osteosarcoma (OS) remains a challenging malignancy with poor prognosis, especially in metastatic or recurrent cases. Despite progress, the molecular mechanisms driving OS, particularly the regulation of Autophagy, are not fully understood. Here, through integrated analysis of single-cell and transcriptomic data, we identify a novel long non-coding RNA (lncRNA), OLMALINC, as a critical Autophagy regulator in OS. OLMALINC is significantly upregulated in OS tissues, with its expression correlating to poor clinical outcomes. Functional studies show that altering OLMALINC expression impacts OS cell progression and Autophagy. Mechanistically, transcriptome analysis and RNA immunoprecipitation reveal Ubiquitin-Specific Peptidase 1 (USP1) as a direct downstream target of OLMALINC. The OLMALINC-USP1 axis inhibits Autophagy and activates the hypoxia-inducible factor 1 (HIF-1α) pathway, promoting OS progression. Therapeutically, combining the USP1 Inhibitor ML-323 with doxorubicin demonstrated synergistic anti-tumor effects in vitro and in vivo, enhancing Autophagy and Apoptosis while inhibiting tumor growth. These findings uncover a novel OLMALINC-USP1-HIF-1α axis in OS progression and highlight the potential of combining Autophagy modulation with chemotherapy for improved therapeutic outcomes.

Keywords

Autophagy; Combination therapy; Lnc OLMALINC; Osteosarcoma; USP1.

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