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UBE2C 被 miR-140-3p 靶向调控,通过 PI3K/AKT 信号通路促进骨肉瘤的进展。

UBE2C, targeted by miR-140-3p, promotes the progression of osteosarcoma via PI3K/AKT signaling pathway.

机构信息

Department of Spinal surgery, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, China.

Department of Operating Room, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, China.

出版信息

J Recept Signal Transduct Res. 2024 Jun;44(3):107-114. doi: 10.1080/10799893.2024.2423100. Epub 2024 Nov 5.

Abstract

BACKGROUND

UBE2C was reported to play carcinogenic effects in diverse cancers. However, the role of UBE2C in osteosarcoma was poorly understood, and its functional mechanisms were not fully clarified.

METHODS

RT-qPCR was used to assess the expression of UBE2C mRNA and miR-140-3p, and western blot technique was used to examine the UBE2C protein and PI3K/AKT pathway-associated proteins. CCK-8 test was applied to measure cell proliferation, and wound healing assay were used to measure migration. Using animal studies, the function of UBE2C was evaluated. Dual-luciferase reporter assay was used to confirm the potential interaction among UBE2C and miR-140-3p.

RESULTS

In osteosarcoma cells as well as tumor samples, UBE2C was strongly expressed. Osteosarcoma cell proliferation as well as cell migration were inhibited by UBE2C knockdown, and PI3K/AKT signaling activity was diminished. In addition, UBE2C knockdown impeded tumor growth in animal models. UBE2C expression was lessened by miR-140-3p as miR-140-3p targets it. UBE2C is overexpressed which promote osteosarcoma proliferation as well as migration, and strengthened the PI3K/AKT signaling activity, while forced miR-140-3p expression partially abolished these effects.

CONCLUSION

UBE2C, targeted by miR-140-3p, drove carcinogenic effects in osteosarcoma through activating the PI3K/AKT pathway.

摘要

背景

UBE2C 已被报道在多种癌症中发挥致癌作用。然而,UBE2C 在骨肉瘤中的作用知之甚少,其功能机制也尚未完全阐明。

方法

采用 RT-qPCR 检测 UBE2C mRNA 和 miR-140-3p 的表达,Western blot 技术检测 UBE2C 蛋白和 PI3K/AKT 通路相关蛋白。CCK-8 试验检测细胞增殖,划痕愈合试验检测细胞迁移。通过动物研究评估 UBE2C 的功能。双荧光素酶报告实验验证 UBE2C 和 miR-140-3p 之间的潜在相互作用。

结果

在骨肉瘤细胞和肿瘤样本中,UBE2C 表达强烈。UBE2C 敲低抑制骨肉瘤细胞增殖和迁移,降低 PI3K/AKT 信号活性。此外,UBE2C 敲低抑制动物模型中的肿瘤生长。miR-140-3p 通过靶向 UBE2C 来减少 UBE2C 的表达。UBE2C 的过表达促进骨肉瘤的增殖和迁移,并增强 PI3K/AKT 信号活性,而强制表达 miR-140-3p 则部分消除了这些效应。

结论

UBE2C 被 miR-140-3p 靶向,通过激活 PI3K/AKT 通路驱动骨肉瘤的致癌作用。

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