Huang Xuanming, Chen Shengye, Wu Chengwei, Urabe Fumihiko, Heidegger Isabel, Campobasso Davide, Huang Hang, Li Ping
Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Otorhinolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Transl Androl Urol. 2025 Jun 30;14(6):1782-1796. doi: 10.21037/tau-2025-316. Epub 2025 Jun 25.
Prostate cancer (PC) remains one of the leading causes of cancer-related mortality, necessitating further research into novel prognostic biomarkers and therapeutic targets. Long noncoding RNA second chromosome locus-associated with prostate-1 (SChLAP1) plays a crucial role in the aggressiveness of PC; however, its precise mechanism remains unclear. This study aimed to investigate the role of SChLAP1 in PC metastasis and apoptosis, with a particular focus on its interaction with miR-101.
The expression levels of SChLAP1 were analyzed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) in 42 clinical specimens, including 21 PC tissues and their corresponding adjacent normal tissues, as well as in PC cell lines (PC-3, DU145, and LNCaP). Functional assays were performed using lentivirus-mediated knockdown and overexpression of SChLAP1 and miR-101-5p. Cell proliferation, invasion, apoptosis, and autophagy were assessed via Cell Counting Kit-8 assays, Transwell migration assays, flow cytometry, and Western blot analysis. Bioinformatics analysis and complementary expression experiments were used to validate the interaction between SChLAP1 and miR-101-5p. An xenograft model was established by subcutaneously implanting PC-3 cells into nude mice to evaluate tumor growth.
SChLAP1 was significantly upregulated in PC tissues and was correlated with higher Gleason scores (P<0.05). Knockdown of SChLAP1 suppressed PC-3 cell proliferation, invasion, and cell cycle progression while promoting apoptosis through MMP-9/Bcl-2 downregulation and caspase-3 activation. SChLAP1 functioned as a cytoplasmic competing endogenous RNA (ceRNA) by directly binding to miR-101-5p. Overexpression of miR-101-5p inhibited metastasis and induced apoptosis but had no significant effect on autophagy. , both SChLAP1 knockdown and miR-101-5p overexpression significantly reduced tumor volume.
SChLAP1 promotes PC progression by regulating metastasis and apoptosis via the miR-101-5p axis. The SChLAP1/miR-101-5p signaling pathway represents a novel diagnostic and therapeutic target, with potential implications for improving prognostic assessment and treatment strategies for advanced PC. Further clinical studies are warranted to evaluate its therapeutic potential in clinical settings.
前列腺癌（PC）仍然是癌症相关死亡的主要原因之一，因此有必要进一步研究新的预后生物标志物和治疗靶点。长链非编码RNA第二染色体位点与前列腺-1相关（SChLAP1）在PC的侵袭性中起关键作用；然而，其确切机制仍不清楚。本研究旨在探讨SChLAP1在PC转移和凋亡中的作用，特别关注其与miR-101的相互作用。
通过定量聚合酶链反应（qPCR）和荧光原位杂交（FISH）分析42例临床标本中SChLAP1的表达水平，包括21例PC组织及其相应的相邻正常组织，以及PC细胞系（PC-3、DU145和LNCaP）。使用慢病毒介导的SChLAP1和miR-101-5p敲低和过表达进行功能测定。通过细胞计数试剂盒-8测定、Transwell迁移测定、流式细胞术和蛋白质印迹分析评估细胞增殖、侵袭、凋亡和自噬。生物信息学分析和互补表达实验用于验证SChLAP1与miR-101-5p之间的相互作用。通过将PC-3细胞皮下植入裸鼠建立异种移植模型以评估肿瘤生长。
SChLAP1在PC组织中显著上调，并且与更高的Gleason评分相关（P<0.05）。敲低SChLAP1可抑制PC-3细胞增殖、侵袭和细胞周期进程，同时通过下调MMP-9/Bcl-2和激活caspase-3促进凋亡。SChLAP通过直接与miR-101-5p结合发挥细胞质竞争性内源RNA（ceRNA）的功能。miR-101-5p的过表达抑制转移并诱导凋亡，但对自噬没有显著影响。SChLAP1敲低和miR-101-5p过表达均显著减小肿瘤体积。
SChLAP1通过miR-101-5p轴调节转移和凋亡来促进PC进展。SChLAP1/miR-101-5p信号通路代表了一个新的诊断和治疗靶点，对改善晚期PC的预后评估和治疗策略具有潜在意义。有必要进行进一步的临床研究以评估其在临床环境中的治疗潜力。
