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Updated: Nov 6, 2025
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis
Hui Zhang1, Minghui Li1, Jing Zhang1
1College of Medical, Huanghuai University, Zhumadian, Henan, People's Republic of China.
Background:
Exosomal circular RNAs (circRNAs) are involved in the pathogenesis of prostate cancer (PCa) and chemotherapy resistance. This research aimed to explore the function and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance of PCa.
Methods:
The expression of circ-XIAP, microRNA-1182 (miR-1182), tumor protein D52 (TPD52) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Exosomes were detected with transmission electron microscopy (TEM). Cluster of differentiation 63 (CD63), cluster of differentiation 9 (CD9) and TPD52 protein levels were detected by Western blot (WB). FIfty percent inhibitory concentration (IC50) of DTX and cell viability were determined using Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was applied to assess colony-forming ability. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Transwell assay was used for measuring cell migration and invasion. Dual-reporter luciferase assay was performed to confirm the interaction between miR-1182 and circ-XIAP or TPD52. The role of circ-XIAP in vivo was confirmed via the mice xenograft model.
Results:
Circ-XIAP and TPD52 were upregulated and miR-1182 was downregulated in DTX-resistant PCa tissue specimens and cell lines. Circ-XIAP was also overexpressed in exosomes from DTX-resistant cells and could be transmitted via exosomes. Circ-XIAP knockdown enhanced DTX sensitivity by suppressing DTX-resistant cell proliferation, migration and invasion and inducing cell cycle arrest and apoptosis. Circ-XIAP directly targeted miR-1182, and the effects of circ-XIAP knockdown were reversed by downregulating miR-1182 in DTX-resistant cells. TPD52 was the target of miR-1182, and its upregulation weakened the promotive effect of miR-1182 on DTX sensitivity. Importantly, circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo.
Conclusion:
Exosomal circ-XIAP promoted DTX resistance of PCa by regulating miR-1182/TPD52 axis, providing a promising therapeutic target for PCa chemotherapy.
Insights
Exosomal circular RNA X-linked inhibitor of apoptosis (circ-XIAP) promotes prostate cancer docetaxel resistance by regulating the miR-1182/TPD52 pathway. Targeting circ-XIAP offers a potential therapeutic strategy for improving chemotherapy outcomes in prostate cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Circular RNAs (circRNAs) are implicated in prostate cancer (PCa) pathogenesis and the development of chemotherapy resistance.
- Exosomal circRNAs play a role in intercellular communication and disease progression.
Purpose of the Study:
- To investigate the functional role and molecular mechanism of circRNA X-linked inhibitor of apoptosis (circ-XIAP) in docetaxel (DTX) resistance in prostate cancer (PCa).
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot (WB) were used to measure gene and protein expression.
- Exosome detection via transmission electron microscopy (TEM).
- Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and Transwell assays assessed proliferation, viability, cell cycle, apoptosis, migration, and invasion.
- Dual-luciferase reporter assays confirmed molecular interactions.
- In vivo efficacy was evaluated using a mice xenograft model.
Main Results:
- Circ-XIAP and TPD52 were upregulated, while miR-1182 was downregulated in DTX-resistant PCa tissues and cells.
- Exosomal circ-XIAP was overexpressed and transferable, promoting DTX resistance.
- Circ-XIAP knockdown enhanced DTX sensitivity by inhibiting proliferation, migration, invasion, and inducing apoptosis, effects reversed by miR-1182 downregulation.
- Circ-XIAP targeted miR-1182, which in turn targeted TPD52, mediating DTX resistance.
- Circ-XIAP depletion inhibited tumor growth and increased DTX sensitivity in vivo.
Conclusions:
- Exosomal circ-XIAP promotes docetaxel resistance in prostate cancer by modulating the miR-1182/TPD52 axis.
- Circ-XIAP represents a promising therapeutic target for overcoming chemotherapy resistance in PCa.
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