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环状 RNA 中线 1(circMID1)促进前列腺癌的增殖、迁移、侵袭和糖酵解。

Circular RNA midline-1 (circMID1) promotes proliferation, migration, invasion and glycolysis in prostate cancer.

机构信息

Department of Uropoiesis Surgical, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China.

Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, China.

出版信息

Bioengineered. 2022 Mar;13(3):6293-6308. doi: 10.1080/21655979.2022.2037367.

Abstract

The key role of circular RNA (circRNA) in the malignant progression of cancers has been demonstrated. However, the role of circRNA midline-1 (circMID1) in prostate cancer (PCa) progression has not been clarified. Quantitative real-time PCR was used to measure relative expression. Function analysis was performed using EdU staining, colony formation assay, flow cytometry, wound healing assay, transwell assay and cell glycolysis detection. The protein levels were detected by Western blot analysis. RNA pull-down assay, dual-luciferase reporter assay and RIP assay were performed to verify RNA interaction. Animal experiments were utilized to explore the effects of circMID1 knockdown on PCa tumorigenesis in vivo. Our results showed that circMID1 was upregulated in PCa tissues and cells and its knockdown inhibited PCa cell proliferation, migration, invasion and glycolysis in vitro, as well as PCa tumorigenesis in vivo. IGF1R and YTHDC2 were highly expressed in PCa tissues and cells, and their expression was positively regulated by circMID1. IGF1R and YTHDC2 overexpression reversed the inhibitory effect of circMID1 silencing on PCa cell progression. In terms of mechanism, circMID1 could sponge miR-330-3p and miR-330-3p could target IGF1R and YTHDC2. Functional experiments showed that circMID1 sponged miR-330-3p to regulate PCa progression via the YTHDC2/IGF1R/AKT axis. In conclusion, our data confirmed that circMID1 might play a pro-cancer role in PCa, which promoted PCa progression through regulating the miR-330-3p/YTHDC2/IGF1R/AKT axis.

摘要

环状 RNA(circRNA)在癌症的恶性进展中起着关键作用。然而,circRNA 中线 1(circMID1)在前列腺癌(PCa)进展中的作用尚未阐明。使用定量实时 PCR 测量相对表达量。通过 EdU 染色、集落形成试验、流式细胞术、划痕愈合试验、transwell 试验和细胞糖酵解检测进行功能分析。通过 Western blot 分析检测蛋白水平。通过 RNA 下拉试验、双荧光素酶报告基因试验和 RIP 试验验证 RNA 相互作用。利用动物实验探讨 circMID1 敲低对 PCa 肿瘤发生的体内影响。我们的结果表明,circMID1 在 PCa 组织和细胞中上调,其敲低抑制了 PCa 细胞的体外增殖、迁移、侵袭和糖酵解以及体内的 PCa 肿瘤发生。IGF1R 和 YTHDC2 在 PCa 组织和细胞中高表达,其表达受 circMID1 的正向调节。IGF1R 和 YTHDC2 的过表达逆转了 circMID1 沉默对 PCa 细胞进展的抑制作用。就机制而言,circMID1 可以海绵 miR-330-3p,而 miR-330-3p 可以靶向 IGF1R 和 YTHDC2。功能实验表明,circMID1 通过 YTHDC2/IGF1R/AKT 轴海绵 miR-330-3p 来调节 PCa 进展。总之,我们的数据证实 circMID1 可能在 PCa 中发挥致癌作用,通过调节 miR-330-3p/YTHDC2/IGF1R/AKT 轴促进 PCa 进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d1c/8973952/2281fdb932fe/KBIE_A_2037367_UF0001_OC.jpg

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