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

Sep 21, 2026

Uploaded by Patrick

Objective: Circular ribose nucleic acids (circRNAs) are implicated in tumor progression and drug resistance of prostate cancer (PCa). This study investigated circ_0005203 (circTHSD4) in PCa malignancy and docetaxel (DTX) resistance. Methods: circTHSD4 expression in PCa and matched non-carcinoma samples was measured by RT-qPCR, with subcellular localization, HMGA2 detection by Western blot, and functional validation by dual-luciferase reporter assays. Cell phenotypes were evaluated via CCK-8, colony formation, Transwell, apoptosis assays, and a xenograft model; results showed circTHSD4 upregulation and miR-203/HMGA2 axis–mediated effects.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Introduction

Prostate cancer background and treatment challenges

Role of circular RNAs (circRNAs) in cancer progression and drug resistance

Methods and experimental assays

Expression, localization, and protein detection

Functional assays and in vivo xenograft verification

ONCOLOGY RESEARCH 2024 32(3): 529-544 CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis JIANYUN XIE 1,*; LINJIE LU 1; JIALI ZHANG 1; 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 Key words: circTHSD4, Docetaxel resistance, Prostate cancer, miR-203, HMGA2 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. Introduction Prostate cancer (PCa) refers to the most commonly diagnosed malignancy in male genitourinary system, ranking as the ﬁfth major reason for cancer-related deaths [1]. In accordance with the epidemiological data among 36 different cancers in 185 different nations, there were 375,304 (3.8%) fatalities and 1,414,259 (7.3%) newly diagnosed cases of PCa in 2020 [2]. Currently, a combination of surgery with adjuvant radiotherapy and chemotherapy remains as the mainstay therapy for PCa patients. Nevertheless, the development of multidrug resistance (MDR) is a pervasive issue in the clinical management of PCa, which has been recognized as the major reason for treatment failure and the mortality in PCa patients[3] . *Address correspondence to: Jianyun Xie, [fcce147@163.com](fcce147@163.com); Weidong Chen, [ch2wd@163.com](ch2wd@163.com) Received: 24 June 2023; Accepted: 15 August 2023; Published: 06 February 2024 Endocrine therapy represents a standard treatment for PCa patients. However, PCa frequently progresses or relapses into androgen-independent prostate cancer (AIPC) and hormone-refractory prostate cancer (HRPC) after continuous endocrine therapy [4] . Docetaxel (DTX) is oneof the most frequently used anticancer drugs for PCa treatment. The standard chemotherapeutic regimen of DTX can signiﬁcantly improve the survival of PCa patients. However, the development of DTX resistance seems to bean inevitable consequence of PCa chemotherapy, and the median survival duration of d

FAQs

What role does circTHSD4 play in prostate cancer?

circTHSD4 is up-regulated in PCa tissues and cells, and its silencing suppresses tumor cell growth, migration, and colony formation while increasing apoptosis and xenograft carcinogenesis.

How was the docetaxel (DTX) resistance effect of circTHSD4 evaluated?

The study used functional assays in PCa cells and constructed a xenograft mouse model. circTHSD4 silencing enhanced DTX sensitivity in PCa cells.

Through which molecular axis does circTHSD4 regulate malignancy?

circTHSD4 modulates PCa malignancy by regulating HMGA2 expression through sponging miR-203, forming the miR-203/HMGA2 axis.

Sep 21, 2026

Uploaded by Patrick