Novel N6-Methyladenosine-Associated lncRNA Model for Predicting Biochemical Recurrence in Patients with Prostate Cancer

Yufan Wu, Qizhong Lu, Xi Zhang, Linya Yao, Xueming Zeng, Qiwei Yu, Weiguo Chen

Article ID: 8122
Vol 38, Issue 6, 2024
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20243806.390
Received: 4 March 2023; Accepted: 4 March 2023; Available online: 20 June 2024; Issue release: 20 June 2024


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Abstract

Background: Prostate cancer (PC) is a solid tumour that is highly prevalent worldwide, ranking as the second most common tumour in humans. The N6-methyladenosine modification of ribonucleic acid (RNA) (m6A) is the most prevalent epigenetic internal modification of both non-coding RNAs (ncRNAs) and messenger RNAs (mRNAs). This study aimed to investigate the link between m6A-related long non-coding RNAs (lncRNAs) and PC to provide a new solution for treating this disease. Methods: This study used a Pearsons correlation analysis to identify m6A-related lncRNAs. The expression and function of AC020907.4, one of the four selected m6A-related lncRNAs, were verified through experimental validation in PC tissue samples and cell lines. In addition, univariate Cox regression was employed to screen these m6A-related lncRNAs for PC. In the validation and entire groups, a least absolute shrinkage and selection operator (LASSO) Cox regression analysis was used to establish and validate the prognostic model for biochemical recurrence (BCR), and small interfering RNA (siRNA) was used to knockdown AC020907.4. Real-time quantitative polymerase chain reaction assay was used to detect the mRNA expression level. A cell counting kit-8 assay was used to detected cell viability. Results: In total, this study identified 204 m6A-related lncRNAs and found that 64 of the 204 were linked with BCR in patients diagnosed with PC. The LASSO Cox regression was employed to establish a BCR model containing four lncRNAs (AC020907.4, AC022364.1, AC099850.3 and AP001505.1). Kaplan–Meier curves confirmed the different outcomes in the low-risk and high-risk groups. The effectiveness of the model was evaluated using receiver operating characteristic and concordance index curves. The independence of the model for the prognosis prediction was analysed using univariate and multivariate Cox regression analyses. The knockdown of AC020907.4 reduced the cell viability of PC cells. Conclusions: This study constructed and validated an m6A-related lncRNA model for BCR prediction in patients with PC, providing new insights for research related to m6A and the clinical treatment of PC.


Keywords

prostate cancer;N6-methyladenosine-associated lncRNA;m6A;prognostic model;biochemical recurrence


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