研究动态
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CircDHRS3通过circDHRS3/miR-421/MEIS2轴抑制前列腺癌细胞的增殖和转移。

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

发表日期:2023 Dec
作者: Xiyu Dai, Xinan Chen, Wensun Chen, Yuxi Ou, Yiling Chen, Siqi Wu, Quan Zhou, Chen Yang, Limin Zhang, Haowen Jiang
来源: Epigenetics

摘要:

前列腺癌是男性全球最常见的癌症类型。环状RNA (circRNA) 在前列腺癌中的重要性及其与恶性的联系已得到逐渐认识。通过前列腺癌的circRNA测序获得circRNA表达,进一步分析circRNA及其功能。通过qRT-PCR、RIP测定、FISH、RNA pulldown、WB、CCK-8、群体形成实验和伤口愈合实验进行验证。使用BALB/ c裸鼠作为异种移植宿主。在前列腺癌中评估了circDHRS3的低表达。circDHRS3的过表达抑制前列腺癌在体外生长和迁移。此外,通过荧光原位杂交和双荧光素酶实验,显示miR-421是circDHRS3的下游靶标。针对PC3和Du145细胞系的救援实验结果表明,通过circDHRS3/miR-421/MEIS2轴调节MEIS2表达可以抑制前列腺癌细胞系的增殖和转移。体内研究证实,circDHRS3的过表达可以抑制前列腺癌细胞的肺部和骨骼转移。circDHRS3具有成为前列腺癌生物标志物和靶向治疗位点的潜力,特别是在恶性阶段。我们的研究表明,circDHRS3通过circDHRS3/miR-421/MEIS2轴抑制前列腺癌细胞的增殖和转移。
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.