Chongqing medical university, The third affiliated hospital (General Hospital), Department of urology, 401120 Chongqing, China.
Chongqing north KuanRen hospital, 400000 Chongqing, China.
Bull Cancer. 2021 Apr;108(4):359-368. doi: 10.1016/j.bulcan.2020.11.022. Epub 2021 Mar 18.
Overexpression of certain long non-coding RNAs (lncRNAs) promotes the progression of castration-resistant prostate cancer (CRPC). The significance and potential role of the lncRNA designated pituitary tumour-transforming 3, pseudogene (PTTG3P) in CRPC is unknown.
We detected PTTG3P expression by qPCR. Upregulated PTTG3P expression was performed to explore the role of PTTG3P in PCa cells resistant to ADT (androgen deprivation therapy). The relationship among PTTG3P, mir-146a-3p and PTTG1 were validated by qPCR, western blot and luciferase assay.
PTTG3P levels were significantly increased in the androgen-independent PC cell lines, as well as in CRPC tissues compared with those of the androgen-dependent prostate cancer cell line LNCaP and tumour tissues of patients with hormone-naive prostate cancers. Enforced expression of PTTG3P in androgen-deprived LNCaP cells significantly enhanced survival, clonogenicity, and tumorigenicity. Further, PTTG3P acted as a competing endogenous RNA (ceRNA, natural miRNA sponge) to upregulate PTTG1 expression by competing for mir-146a-3p in the progression to CRPC.
Our findings suggest that PTTG3P promotes the resistance of prostate cancer cells to androgen-deprivation therapy via upregulating PTTG1. PTTG3P may therefore represent a potential target for therapy of CRPC.
某些长链非编码 RNA（lncRNA）的过表达促进了去势抵抗性前列腺癌（CRPC）的进展。垂体肿瘤转化基因 3 假基因（PTTG3P）在 CRPC 中的意义和潜在作用尚不清楚。
我们通过 qPCR 检测 PTTG3P 的表达。上调 PTTG3P 的表达，以探讨 PTTG3P 在对 ADT（雄激素剥夺疗法）耐药的前列腺癌细胞中的作用。通过 qPCR、western blot 和荧光素酶测定验证 PTTG3P、mir-146a-3p 和 PTTG1 之间的关系。
与雄激素依赖性前列腺癌细胞系 LNCaP 和激素初治前列腺癌患者的肿瘤组织相比，雄激素非依赖性 PC 细胞系以及 CRPC 组织中 PTTG3P 水平显著升高。在雄激素剥夺的 LNCaP 细胞中强制表达 PTTG3P 显著增强了存活、集落形成和致瘤性。此外，PTTG3P 作为竞争性内源性 RNA（ceRNA，天然 miRNA 海绵），通过与 mir-146a-3p 竞争，上调 PTTG1 的表达，从而促进 CRPC 的进展。
我们的研究结果表明，PTTG3P 通过上调 PTTG1 促进前列腺癌细胞对雄激素剥夺治疗的耐药性。因此，PTTG3P 可能成为 CRPC 治疗的潜在靶点。
