Open Access

ARTICLE

CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis

by JIANYUN XIE^1,*, LINJIE LU¹, JIALI ZHANG¹, QIRUI LI², WEIDONG CHEN^1,*

1 Department of Urology, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
2 Department of Internal Medicine Outpatient Clinic, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China

* Corresponding Authors: JIANYUN XIE. Email: ; WEIDONG CHEN. Email:

Oncology Research 2024, 32(3), 529-544. https://doi.org/10.32604/or.2023.031511

Received 24 June 2023; Accepted 15 August 2023; Issue published 06 February 2024

Abstract

Objective: Circular ribose nucleic acids (circRNAs) are implicated in tumor progression and drug resistance of prostate cancer (PCa). The current work explored the function of circ_0005203 (circTHSD4) in the malignancy and docetaxel (DTX) resistance of PCa. Methods: circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells. In addition, we performed a Western blot (WB) assay to detect high-mobility-group A2 protein (HMGA2) levels. Besides, functional associations of two molecules were investigated through dual luciferase reporter assay. Cell Counting Kit (CCK)-8, colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells, whereas flow cytometry was performed to determine cell apoptosis. Furthermore, a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells. Results: According to RT-qPCR results, circTHSD4 was up-regulated within PCa tissues and cells, which predicted the dismal prognostic outcome of PCa cases. circTHSD4 silencing within PCa cells markedly suppressed cell growth, migration, and colony formation. circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model. Further, circTHSD4 silencing enhanced docetaxel (DTX) sensitivity in PCa cells. Furthermore, we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR-203. Conclusion: Together, our findings suggest that circTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR-203/HMGA2 axis.

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