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Unveiling the oncogenic role of lncRNA PIG13-DT in hepatocellular carcinoma progression.

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Cancer biology & therapy 2025 Vol.26(1) p. 2567797
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Cai H, Chen S, Tang S, Shi F, Zeng D, Wu Z, Wang F, Huang S, Li D, Guo W

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[BACKGROUND] Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality due to delayed diagnosis and poor prognosis.

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APA Cai H, Chen S, et al. (2025). Unveiling the oncogenic role of lncRNA PIG13-DT in hepatocellular carcinoma progression.. Cancer biology & therapy, 26(1), 2567797. https://doi.org/10.1080/15384047.2025.2567797
MLA Cai H, et al.. "Unveiling the oncogenic role of lncRNA PIG13-DT in hepatocellular carcinoma progression.." Cancer biology & therapy, vol. 26, no. 1, 2025, pp. 2567797.
PMID 41065761

Abstract

[BACKGROUND] Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality due to delayed diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are key cancer regulators, yet the role of C1orf21-DT (PIG13-DT) in HCC remains unclear.

[METHODS] We evaluated PIG13-DT expression in HCC and paired adjacent non-tumorous tissues. Functional studies were conducted using cell culture, cell-derived xenotransplantation (CDX) models, and molecular techniques including RNA pull-down, mass spectrometry, RIP-qPCR, and RNA sequencing. We explored the interplay between PIG13-DT, RNA-binding protein YBX3, and USP15 mRNA.

[RESULTS] PIG13-DT was highly expressed in HCC tissues compared with normal tissues and associated with poor prognosis. Functionally, PIG13-DT enhanced cancer stem cell (CSC) function, reduced reactive oxygen species (ROS) levels, and promoted HCC cell proliferation and migration. Mechanistically, PIG13-DT interacted with YBX3, stabilizing YBX3 and promoting USP15 mRNA translation and stability, thus driving HCC progression. Clinical data from lenvatinib-treated HCC patients showed that PIG13-DT expression was correlated with poor treatment response.

[CONCLUSION] Our study identifies a novel PIG13-DT/YBX3/USP15 axis driving HCC progression, suggesting PIG13-DT as a potential biomarker and therapeutic target. This work provides new insights into HCC molecular mechanisms and offers potential diagnostic and therapeutic implications.

MeSH Terms

Carcinoma, Hepatocellular; Humans; Liver Neoplasms; RNA, Long Noncoding; Animals; Disease Progression; Mice; Cell Proliferation; Male; Female; Gene Expression Regulation, Neoplastic; Prognosis; Cell Line, Tumor; Middle Aged; Cell Movement

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