Hsa_circ_0102485 通过调控 miR-188-3p/ARID5B/AR 轴抑制前列腺癌中癌细胞的生长。

Hsa_circ_0102485 inhibits the growth of cancer cells by regulating the miR-188-3p/ARID5B/AR axis in prostate carcinoma.

机构信息

Yunnan Institute of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China; Zhongshan City People's Hospital, Zhongshan 528403, China.

Yunnan Institute of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China.

出版信息

Pathol Res Pract. 2022 Sep;237:154052. doi: 10.1016/j.prp.2022.154052. Epub 2022 Jul 30.

DOI:10.1016/j.prp.2022.154052

PMID:35939970

Abstract

BACKGROUND

Studies have shown that circular RNAs (circRNAs) have significant potential as novel molecular markers for the diagnosis, treatment, and prognosis of prostate carcinoma (PCa). However, the role and mechanism of circRNA hsa_circ_0102485 in PCa remains unclear.

MATERIALS & METHODS: The real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantify hsa_circ_0102485 expression in PCa. The potential mechanisms and roles of hsa_circ_0102485 in tumor growth were explored using dual-luciferase-reporter and subcutaneous-xenograft assays, rescue experiments, and immunohistochemical staining. Clinical correlations were assessed by tissue-on-a-chip in-situ hybridization and Fisher's exact test.

RESULTS

Hsa_circ_0102485 expression was decreased in PCa, and overexpression of hsa_circ_0102485 suppressed the proliferation, metastasis, invasion, and antiapoptotic abilities of PCa cells. MicroRNA 188-3p (MiR-188-3p) is a direct target of hsa_circ_0102485, and cotransfection of hsa_circ_0102485 in PCa cells overexpressing miR-188-3p inhibited its promotive effects. Hsa_circ_0102485 indirectly promotes the expression of AT-rich interaction domain 5B (ARID5B) and androgen receptor (AR) by sponging miR-188-3p and inhibiting PCa cell growth. Correlation analysis showed that hsa_circ_0102485 expression in PCa was not significantly correlated with the age, International Society of Urologic Pathologists (ISUP) grade, Gleason score, or lymph node metastasis status of PCa patients.

CONCLUSION

Hsa_circ_0102485 plays an inhibitory role in PCa by regulating the Mir-188-3p/ARID5B/AR axis and may be a potential diagnostic biomarker and therapeutic target for PCa that requires further study.

摘要

背景

研究表明，环状 RNA（circRNA）作为前列腺癌（PCa）诊断、治疗和预后的新型分子标志物具有重要潜力。然而，circRNA hsa_circ_0102485 在 PCa 中的作用和机制尚不清楚。

材料与方法

采用实时定量逆转录聚合酶链反应（qRT-PCR）检测 PCa 中 hsa_circ_0102485 的表达。通过双荧光素酶报告基因和皮下移植实验、挽救实验和免疫组织化学染色，探讨 hsa_circ_0102485 在肿瘤生长中的潜在机制和作用。通过组织芯片原位杂交和 Fisher 确切检验评估临床相关性。

结果

hsa_circ_0102485 在 PCa 中表达下调，过表达 hsa_circ_0102485 抑制 PCa 细胞的增殖、转移、侵袭和抗凋亡能力。miR-188-3p（miR-188-3p）是 hsa_circ_0102485 的直接靶标，在过表达 miR-188-3p 的 PCa 细胞中转染 hsa_circ_0102485 抑制了其促进作用。hsa_circ_0102485 通过海绵吸附 miR-188-3p 间接促进富含 AT 相互作用域 5B（ARID5B）和雄激素受体（AR）的表达，抑制 PCa 细胞生长。相关性分析表明，hsa_circ_0102485 在 PCa 中的表达与 PCa 患者的年龄、国际泌尿病理学会（ISUP）分级、Gleason 评分或淋巴结转移状态无显著相关性。