Department of Urology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, P.R. China.
Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
Int J Oncol. 2022 Sep;61(3). doi: 10.3892/ijo.2022.5400. Epub 2022 Jul 29.
Prostate cancer (PCa) is one of the principal causes of cancer‑related death worldwide. The roles and mechanisms of long non‑coding RNA (lncRNA) involved in the development of PCa remain incompletely understood. The present study aimed to investigate the role and mechanism of lncRNA in PCa tumorigenesis. In the present study, lncRNA cancer susceptibility candidate 11 (CASC11) was revealed to be a crucial regulator of PCa progression. The expression profiles of CASC11 in PCa were identified through analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets, and validated in human PCa specimens and cell lines. Gain‑ and loss‑of‑function assays were utilized to explore the biological role of CASC11 in PCa initiation and progression. RNA‑sequencing, RNA pull‑down and RNA immunoprecipitation analyses were used to explore potential mechanisms with which CASC11 may be associated. Rescue experiments were further conducted to confirm this association. The present results revealed that CASC11 was dominantly distributed in the nuclei of PCa cells, and was highly expressed in PCa tissues and cells. Overexpression of CASC11 was markedly associated with increased tumor proliferation and migratory ability. Functionally, decreased proliferation and migration, as well as inhibited xenograft tumor growth, were observed in CASC11‑silenced PCa cells, whereas the opposite effects were detected in CASC11‑overexpressing cells. Mechanistically, CASC11 promoted progression of the cell cycle and competitively interacted with Y‑box binding protein 1 (YBX1) to block the p53 pathway. Given this, poly (β‑amino ester) (PBAE)/small interfering RNA‑CASC11 (si‑CASC11) nanoparticles were applied to inhibit CASC11 expression and enhance the antitumor effect . The results revealed that PBAE/si‑CASC11 nanoparticles augmented the antitumor efficacy of CASC11 knockdown . In conclusion, the present study suggested that CASC11 may regulate PCa progression and elucidated a novel CASC11/YBX1/p53 signaling axis, providing a potential lncRNA‑directed therapeutic strategy particularly for the treatment of patients with PCa.
前列腺癌 (PCa) 是全球癌症相关死亡的主要原因之一。长链非编码 RNA (lncRNA) 在 PCa 发展中的作用和机制尚不完全清楚。本研究旨在探讨 lncRNA 在 PCa 发生中的作用和机制。本研究发现，lncRNA 癌症易感性候选基因 11 (CASC11) 是 PCa 进展的关键调节因子。通过分析癌症基因组图谱和基因表达综合数据库，确定了 CASC11 在 PCa 中的表达谱，并在人 PCa 标本和细胞系中进行了验证。通过 gain- 和 loss-功能测定来探讨 CASC11 在 PCa 起始和进展中的生物学作用。利用 RNA 测序、RNA 下拉和 RNA 免疫沉淀分析来探讨 CASC11 可能与之相关的潜在机制。进一步进行了挽救实验来证实这种关联。本研究结果表明，CASC11 主要分布在 PCa 细胞的核内，在 PCa 组织和细胞中高表达。CASC11 的过表达与肿瘤增殖和迁移能力的增加显著相关。功能上，CASC11 沉默的 PCa 细胞中观察到增殖和迁移减少以及异种移植肿瘤生长受到抑制，而在 CASC11 过表达的细胞中则检测到相反的效果。机制上，CASC11 促进细胞周期的进展，并与 Y 盒结合蛋白 1 (YBX1) 竞争相互作用以阻断 p53 通路。鉴于此，应用聚 (β-氨基酯) (PBAE)/小干扰 RNA-CASC11 (si-CASC11) 纳米粒抑制 CASC11 表达并增强抗肿瘤作用。结果表明，PBAE/si-CASC11 纳米粒增强了 CASC11 敲低的抗肿瘤疗效。综上所述，本研究表明 CASC11 可能调节 PCa 的进展，并阐明了一个新的 CASC11/YBX1/p53 信号轴，为特别是治疗 PCa 患者提供了一种潜在的 lncRNA 靶向治疗策略。
