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Clinical and Translational Oncology
Erschienen in: Clinical and Translational Oncology 11/2023

15.05.2023 | RESEARCH ARTICLE

LncRNA OTUD6B-AS1 overexpression promoted GPX4-mediated ferroptosis to suppress radioresistance in colorectal cancer

verfasst von: Zilang Zhang, Baolong Ye, Yiban Lin, Wenjun Liu, Jianzhong Deng, Wu Ji

Erschienen in: Clinical and Translational Oncology | Ausgabe 11/2023

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Abstract

Background

Radiotherapy is widely employed in colorectal cancer (CRC) treatment but is often compromised by developed radioresistance. This study explored the mechanism of long non-coding RNA ovarian tumor domain containing 6B-antisense RNA1 (lncRNA OTUD6B-AS1) in CRC radioresistance through tripartite motif 16 (TRIM16).

Methods

CRC and non-cancerous tissues were collected and radioresistant CRC cells were established, with real-time quantitative polymerase chain reaction to determine gene expression in tissues and cells. Radioresistance was evaluated by cell counting kit-8 assay and immunofluorescence (γ-H2AX) and ferroptosis was tested by Western blot assay (ACSL4/GPX4) and assay kits (Fe2+/ROS/MDA/GSH). The association between ferroptosis and lncRNA OTUD6B-AS1-inhibited radioresistance was testified using ferroptosis inhibitor. The subcellular localization of lncRNA OTUD6B-AS1 was tested by the nuclear/cytoplasmic fractionation assay, with RNA immunoprecipitation assay to validate gene interactions. Rescue experiments were conducted to analyze the role of TRIM16 in CRC radioresistance.

Results

LncRNA OTUD6B-AS1 and TRIM16 were poorly expressed (P < 0.01) in CRC tissues and cells and further decreased (P < 0.01) in radioresistant CRC cells. OTUD6B-AS1 overexpression decreased cell survival (P < 0.01), increased γ-H2AX levels (P < 0.01), and elevated ferroptosis and oxidative stress (P < 0.01) after X-ray radiation. Ferroptosis inhibitor attenuated radioresistance (P < 0.01) caused by lncRNA OTUD6B-AS1 overexpression. LncRNA OTUD6B-AS1 stabilized TRIM16 mRNA via binding to HuR. TRIM16 knockdown reduced ferroptosis and increased radioresistance (P < 0.05).

Conclusion

OTUD6B-AS1 overexpression stabilized TRIM16 via binding to HuR and increased GPX4-mediated ferroptosis, thus attenuating CRC radioresistance. Our study provided a new rationale for the treatment of CRC.
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Metadaten
Titel
LncRNA OTUD6B-AS1 overexpression promoted GPX4-mediated ferroptosis to suppress radioresistance in colorectal cancer
verfasst von
Zilang Zhang
Baolong Ye
Yiban Lin
Wenjun Liu
Jianzhong Deng
Wu Ji
Publikationsdatum
15.05.2023
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 11/2023
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-023-03193-7

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