DHT-Induced lncRNA AC092718.4 Promotes Prostate Cancer Cell Proliferation via ceRNA Mechanism

Background/Objectives: The androgen receptor (AR)-driven transcriptional program plays a pivotal role in the development and progression of prostate cancer. The binding of androgen dihydrotestosterone (DHT) to AR initiates transcriptional activation, thereby altering the transcriptional landscape. DHT-induced long non-coding RNAs (lncRNAs) have been recognized as crucial players in prostate cancer pathogenesis. This study aims to identify and explore the important role of such lncRNAs in prostate cancer. Methods: This study first analyzed transcriptome data from an androgen-dependent cell line, LNCaP, treated with different DHT concentrations and found a batch of lncRNAs exhibiting DHT concentration dependence. TCGA data suggested a correlation between the DHT-induced lncRNA and prostate cancer. Finally, a series of in vivo and in vitro experiments confirmed the effect and mechanism of lncRNA in prostate cancer. Results: AC092718.4 was highly expressed in AR-positive prostate cancer cell lines and tissues, and its expression in patients with Gleason scores 6–9 was significantly higher than in a normal control group. Notably, the expression level of AC092718.4 was upregulated in a concentration-dependent manner with DHT. In vitro experiments revealed that overexpression of AC092718.4 promoted cell proliferation and inhibited cell apoptosis. Conversely, knockdown of AC092718.4 suppressed tumorigenesis in vivo. Furthermore, our investigation into the pathogenetic mechanism demonstrated that AC092718.4 could act as an miRNA sponge for miR-138-5p, attenuating its inhibitory effect on downstream oncogenes, such as FERMT2, RHOC, and HIF1A. These AC092718.4/miR-138-5p/mRNA axes, in turn, facilitated the progression of prostate cancer. Conclusions: For the first time, we demonstrate that AC092718.4 may function as an oncogenic factor in prostate cancer. The AC0927.8.4/miR-138-5p/mRNA axes potentially offer promising diagnostic and therapeutic targets for prostate cancer.