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. 2025 Apr;132(7):587-598.
doi: 10.1038/s41416-025-02938-1. Epub 2025 Feb 16.

The long noncoding RNA lncZBTB10 facilitates AR function via S-palmitoylation to promote prostate cancer progression and abiraterone resistance

Shin-Chih Lin #  1 , Yu-Sheng Cheng #  2 , Yi-Syuan Lin  1 , Thi My Hang Nguyen  3 , Wen-Tai Chiu  1   3   4 , Ya-Chuan Tsai  1 , Hsing-Yi Chen  2 , Tsung-Yen Lin  2 , Shih-Chieh Lin  5   6   7
Affiliations

The long noncoding RNA lncZBTB10 facilitates AR function via S-palmitoylation to promote prostate cancer progression and abiraterone resistance

Shin-Chih Lin et al. Br J Cancer. 2025 Apr.

Abstract

Background: Activation of androgen receptor (AR) by androgen binding to its ligand-binding domain (LBD) has led to the development of clinical drugs that target androgen biosynthesis or the LBD of AR for the treatment of prostate cancer patients. While these drugs initially offer clinical benefits, the emergence of drug resistance is inevitable after a certain duration of treatment.

Objectives: Exploring alternative AR domains or identifying novel mechanisms for AR activation is crucial for advancing prostate cancer therapies.

Methods: A systematic bioinformatic analysis identified novel androgen-responsive long noncoding RNAs (lncRNAs) in prostate cancer, which were verified using loss-of-function and gain-of-function strategies in vitro and in vivo.

Results: lncZBTB10 or LINC02986 was overexpressed in prostate cancer specimens and correlated with poor clinical outcomes. Mechanistically, our findings elucidate the pivotal role of lncZBTB10 in facilitating AR function by inducing S-palmitoylation. Moreover, the interaction between lncZBTB10 and AR not only fosters but also orchestrates biomolecular condensates within the nucleus driven by a novel RNA-binding domain, particularly in prostate cancer cells. Notably, the overexpression of lncZBTB10 not only promotes tumor growth in vivo but also triggers abiraterone resistance in vitro by inducing AR expression.

Conclusions: These results collectively reveal a novel mechanism by which lncZBTB10 regulates AR function in prostate cancer cells.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: We have confirmed that all methods were performed in accordance with the relevant guidelines and regulations. Approval for all the animal studies was obtained from the Institutional Animal Care and Use Committee (IACUC: 108299) at the Laboratory Animal Center, NCKU.

References

    1. Ji Y, Zhang R, Han X, Zhou J. Targeting the N-terminal domain of the androgen receptor: The effective approach in therapy of CRPC. Eur J Med Chem. 2023;247:115077. - PubMed
    1. Huggins C. Prostatic cancer treated by orchiectomy; the five year results. J Am Med Assoc. 1946;131:576–81. - PubMed
    1. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005. - PMC - PubMed
    1. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97. - PubMed
    1. Mostaghel EA, Plymate SR, Montgomery B. Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit. Clin Cancer Res. 2014;20:791–8. - PMC - PubMed

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