AAT resistance-related AC007405.2 and AL354989.1 as novel diagnostic and prognostic markers in prostate cancer

作者全名：Deng, Yuanzhong; Zhang, Chunlin; Yu, Haitao; Chen, Guo; Peng, Xiang; Li, Yang; Feng, Zhenwei; Shi, Wei; Bai, Xuesong; Gou, Xin; Liu, Nian

作者地址：[Deng, Yuanzhong; Zhang, Chunlin; Yu, Haitao; Chen, Guo; Peng, Xiang; Li, Yang; Feng, Zhenwei; Shi, Wei; Bai, Xuesong; Gou, Xin; Liu, Nian] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400016, Peoples R China; [Zhang, Chunlin; Yu, Haitao; Chen, Guo; Peng, Xiang; Li, Yang; Feng, Zhenwei; Shi, Wei; Bai, Xuesong] Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China

通信作者：Gou, X; Liu, N (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing 400016, Peoples R China.

来源：AGING-US

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001216911200034

JCR分区：Q2

影响因子：3.9

年份：2024

卷号：16

期号：8

开始页：7249

结束页：7266

文献类型：Article

关键词：prostate cancer; lncRNA; AAT resistance; risk score model; prostate cancer diagnosis

摘要：Objective: Prostate cancer (PCa) is the second disease threatening men's health, and anti-androgen therapy (AAT) is a primary approach for treating this condition. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in the development of PCa and the process of AAT resistance. The objective of this study is to utilize bioinformatics methods to excavate lncRNAs association with AAT resistance and investigate their biological functions. Methods: AAT resistance-related risk score model (ARR-RSM) was established by multivariate Cox analysis. Paired clinical tissue samples of 36 PCa patients and 42 blood samples from patients with PSA over 4 ng/ml were collected to verify the ARR-RSM. In vitro, RT-qPCR, CCK-8 and clone formation assays were displayed to verify the expression and function of AL354989.1 and AC007405.2. Results: Pearson correlation analysis identified 996 lncRNAs were associated with AAT resistance (ARR-LncRs). ARR-RSM was established using multivariate Cox regression analysis, and PCa patients were divided into high-risk and low-risk groups. High-risk patients showed increased expression of AL354989.1 and AC007405.2 had poorer prognoses. The high-risk score correlated with advanced T-stage and N-stage. The AUC of ARR-RSM outperformed tPSA in diagnosing PCa. Silencing of AC007405.2 and AL354989.1 inhibited PCa cells proliferation and AAT resistance. Conclusions: In this study, we have discovered the clinical significance of AC007405.2 and AL354989.1 in predicting the prognosis and diagnosing PCa patients. Furthermore, we have confirmed their correlation with various clinical features. These findings provide potential targets for PCa treatment and a novel diagnostic and predictive indicator for precise PCa diagnosis.

基金机构：Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) [2020ZLXM004]; Science and Technology Commission of Yuzhong District of Chongqing [20190104]

基金资助正文：This research was funded by Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau), Grant Number 2020ZLXM004; Science and Technology Commission of Yuzhong District of Chongqing, Grant Number 20190104.