Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Department of Urology, Health Examination Center, Obstetrics and Gynecology, and Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050051, China.
Biomed Res Int. 2020 Aug 20;2020:7586521. doi: 10.1155/2020/7586521. eCollection 2020.
cir-ITCH, a well-known tumor-suppressive circular RNA, plays a critical role in different cancers. However, its expression and functional role in prostate cancer (PCa) are unclear. Herein, we explored the potential mechanism and tumor-inhibiting role of cir-ITCH in PCa. Using reverse transcriptase polymerase chain reaction assay, we analyzed the expression of cir-ITCH in PCa and paired adjacent nontumor tissue samples resected during surgical operation, as well as in two cell lines of human PCa (LNCaP and PC-3) and the immortalized normal prostate epithelial cell line (RWPE-1). Cell viability and migration of PCa cell lines were evaluated using CCK-8 and wound-healing assays. Expression of key proteins of the Wnt/-catenin and PI3K/AKT/mTOR pathways was detected using western blotting. We found that cir-ITCH expression was typically downregulated in the tissues and cell lines of PCa compared to that in the peritumoral tissue and in RWPE-1 cells, respectively. The results showed that cir-ITCH overexpression significantly inhibits the proliferation, migration, and invasion of human PCa cells and that reciprocal inhibition of expression occurred between cir-ITCH and miR-17. Proteins in the Wnt/-catenin and PI3K/AKT/mTOR pathways were downregulated by overexpression of cir-ITCH both in androgen receptor-positive LNCaP cells and androgen receptor-negative PC-3 cells. Taken together, these data demonstrated that cir-ITCH plays a tumor-suppressive role in human PCa cells, partly through the Wnt/-catenin and PI3K/AKT/mTOR pathways. Thus, cir-ITCH may serve as a novel therapeutic target for the treatment of PCa, especially castration-resistant prostate cancer.
环状 RNA ITCH（cir-ITCH）是一种已知的肿瘤抑制性环状 RNA，在不同癌症中发挥着关键作用。然而，其在前列腺癌（PCa）中的表达和功能作用尚不清楚。在此，我们探讨了 cir-ITCH 在 PCa 中的潜在机制和肿瘤抑制作用。通过逆转录聚合酶链反应（RT-PCR）检测，我们分析了 cir-ITCH 在 PCa 及手术切除的配对相邻非肿瘤组织样本中的表达，以及在两种人前列腺癌细胞系（LNCaP 和 PC-3）和永生化正常前列腺上皮细胞系（RWPE-1）中的表达。通过 CCK-8 法和划痕愈合实验评估了 PCa 细胞系的细胞活力和迁移。使用 Western blot 检测 Wnt/-catenin 和 PI3K/AKT/mTOR 通路的关键蛋白的表达。我们发现，与周围肿瘤组织和 RWPE-1 细胞相比，PCa 组织和细胞系中 cir-ITCH 的表达通常下调。结果表明，cir-ITCH 过表达可显著抑制人前列腺癌细胞的增殖、迁移和侵袭，并且 cir-ITCH 与 miR-17 之间存在表达的相互抑制关系。在雄激素受体阳性的 LNCaP 细胞和雄激素受体阴性的 PC-3 细胞中，过表达 cir-ITCH 均可下调 Wnt/-catenin 和 PI3K/AKT/mTOR 通路中的蛋白。综上所述，这些数据表明 cir-ITCH 在人前列腺癌细胞中发挥肿瘤抑制作用，部分通过 Wnt/-catenin 和 PI3K/AKT/mTOR 通路。因此，cir-ITCH 可能成为治疗 PCa，特别是去势抵抗性前列腺癌的一种新的治疗靶点。
