CircDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis

Prostate cancer is the most prevalent type of cancer among men worldwide. The importance of circular RNA (circRNA) in prostate cancer and its connection to malignancy has been steadily recognized. circRNA expression was obtained by circRNA sequencing of prostate cancer. circRNA and its function were further analysed. The results were verified by qRT-PCR, RIP assay, FISH, RNA pulldown, WB, CCK-8, colony formation assay and wound-healing assay. BALB/c Nude mice were used for xenograft hosts. Low expression of circDHRS3 was assessed in prostate cancer. Overexpression of circDHRS3 inhibited prostate cancer growth and migration in vitro. Additionally, miR-421 was shown to be the downstream target of circDHRS3, as shown by fluorescence in situ hybridization and dual-luciferase experiments. The rescue assay results for the PC3 and Du145 cell lines demonstrated that circDHRS3 inhibits prostate cancer cell lines’ ability to proliferate and metastasize by modulating MEIS2 expression through the circDHRS3/miR-421/MEIS2 axis. In vivo investigations confirmed that the overexpression of circDHRS3 could inhibit both the lung and bone metastasis of prostate cancer cells. circDHRS3 has the potential to become a biomarker and a targeted therapeutic site for prostate cancer, particularly in the malignant stage. Our study indicates that circDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis.前列腺癌是全球男性中发病率最高的癌症类型。环状RNA（circular RNA, circRNA）在前列腺癌中的生物学作用及其与肿瘤恶性表型的关联正逐步获得学界认可。本研究通过对前列腺癌样本进行环状RNA测序获取circRNA表达谱，对circRNA及其功能展开深入分析，并通过实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）、RNA免疫沉淀（RNA immunoprecipitation, RIP）实验、荧光原位杂交（fluorescence in situ hybridization, FISH）、RNA pull-down、蛋白质印迹（Western Blot, WB）、细胞计数试剂盒-8（Cell Counting Kit-8, CCK-8）、克隆形成实验及划痕愈合实验对研究结果进行验证。实验采用BALB/c裸鼠作为异种移植宿主。研究发现，circDHRS3在前列腺癌组织中呈低表达状态；过表达circDHRS3可在体外抑制前列腺癌细胞的增殖与迁移能力。此外，通过荧光原位杂交与双荧光素酶实验证实，miR-421是circDHRS3的下游靶标分子。针对PC3与Du145细胞系的挽救实验结果表明，circDHRS3可通过circDHRS3/miR-421/MEIS2调控轴调控MEIS2的表达，进而抑制前列腺癌细胞的增殖与转移能力。体内实验进一步证实，过表达circDHRS3可有效抑制前列腺癌细胞的肺转移与骨转移。综上，circDHRS3有望成为前列腺癌，尤其是肿瘤恶性进展阶段的生物标志物及靶向治疗靶点。本研究揭示，circDHRS3可通过circDHRS3/miR-421/MEIS2信号轴抑制前列腺癌细胞的增殖与转移过程。