Abstract：Objective: To investigate the effects and molecular mechanisms of long non-coding RNA (LncRNA) DNA damage activated (NORAD) on docetaxel resistance in castration-resistant prostate cancer (CRPC) cells by regulating thyroid hormone receptor interactor 13 (TRIP13) and the autophagy pathway. Methods: The sensitivity of CRPC cell line PC3 and its docetaxel-resistant strain PC3-DR to docetaxel was compared. PC3-DR cells were divided into 8 groups, including Control group, NORAD silenced group, NORAD silenced negative control group, TRIP13 silenced group, TRIP13 silenced negative control group, NORAD silenced + TRIP13 overexpression group, NORAD silenced + TRIP13 overexpression negative control group, and NORAD silenced + 3-MA (autophagy inhibitor) group. EdU assay was used to detect proliferation, flow cytometry was used to detect apoptosis, scratch assay and Transwell assay were used to analyze migration and invasion. qRT-PCR was used to detect the expression of LncRNA NORAD. Western blot was used to detect the expression of TRIP13, Beclin1, LC3-II/I, and p62 proteins. Each group of PC3-DR cells was treated with docetaxel, and EdU assay and flow cytometry were used to detect proliferation and apoptosis, respectively, to analyze the changes in docetaxel sensitivity. Results: Compared with the PC3 group, the PC3-DR group showed significantly reduced inhibition rates of proliferation, migration, and invasion, and reduced apoptosis promotion rate after docetaxel treatment (P<0.05). Compared with the Control group and NORAD silenced negative control group, the NORAD silenced group showed significantly reduced cell proliferation, migration, and invasion (P<0.05), with significantly downregulated expression of LncRNA NORAD and TRIP13, significantly upregulated LC3-II/I ratio and Beclin1, and significantly downregulated p62 (all P<0.05). Compared with the Control group or NORAD silenced negative control group, the TRIP13 silenced group showed significantly downregulated expression of TRIP13, significantly upregulated LC3-II/I ratio and Beclin1, and significantly downregulated p62 (all P<0.05). Overexpression of TRIP13 or 3-MA treatment could partially reverse the effects of NORAD silencing (all P<0.05). Additionally, the proliferation inhibition rate and apoptosis promotion rate of the NORAD silenced group or TRIP13 silenced group were significantly increased compared with the Control group (all P<0.05), and overexpression of TRIP13 or 3-MA treatment could partially reverse the increased effects of NORAD silencing on proliferation inhibition rate and apoptosis promotion rate (all P<0.05). Conclusion: Silencing LncRNA NORAD promotes the sensitivity of PC3-DR cells to docetaxel by inhibiting TRIP13 expression and activating the autophagy pathway, thereby reversing docetaxel resistance in CRPC cells. This provides a theoretical basis for targeting the LncRNA NORAD/TRIP13/autophagy axis in the treatment of drug-resistant prostate cancer.
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2026, Vol. 32 
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