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miR-125a 通过 Rad51 抑制宫颈鳞癌细胞的恶性生物学行为。

miR-125a attenuates the malignant biological behaviors of cervical squamous cell carcinoma cells through Rad51.

机构信息

Department of Pathology, The Second Hospital of Longyan, Longyan, China.

Department of Pathology, Ganzhou People's Hospital, the Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, China.

出版信息

Bioengineered. 2022 Apr;13(4):8503-8514. doi: 10.1080/21655979.2022.2051827.

Abstract

Cervical squamous cell carcinoma (CSCC), the most common cervical malignancy, is more likely to invade and metastasize than other cervical cancers. miR-125a, a tumor suppressor gene, has been confirmed to be associated with cancer metastasis. However, the role of miR-125a in CSCC and the underlying mechanism are unknown. miR-125a expression was confirmed by real-time quantitative PCR (RT-qPCR), and the Rad51 expression level was measured by western blotting analysis. CSCC cell proliferation, migration and invasion were assessed with functional assays, including CCK-8, colony formation, wound healing and Transwell assays. Our data confirmed that miR-125a is expressed at low levels in CSCC tissues and cells. Functionally, the overexpression of miR-125a greatly prevented the proliferation, migration and invasion of CSCC cells, and the inhibition of miR-125a expression strongly enhanced these behaviors in CSCC cells. Moreover, the expression of Rad51, a miR-125a target gene, greatly reversed the miR-125-mediated inhibition of CSCC cell proliferation, migration and invasion. In addition, we discovered that miR-125a downregulated the levels of phosphorylated PI3K, AKT and mTOR through Rad51 in CSCC cells. miR-125a, a tumor suppressor, can attenuate the malignant behaviors of CSCC cells by targeting Rad51. Therefore, the miR-125a/Rad51 axis might be a target for CSCC therapy.

摘要

宫颈鳞状细胞癌(CSCC)是最常见的宫颈癌,比其他宫颈癌更容易侵袭和转移。miR-125a 是一种肿瘤抑制基因,已被证实与癌症转移有关。然而,miR-125a 在 CSCC 中的作用及其潜在机制尚不清楚。通过实时定量 PCR(RT-qPCR)证实了 miR-125a 的表达,通过 Western blot 分析测量了 Rad51 的表达水平。通过 CCK-8、集落形成、划痕愈合和 Transwell 测定等功能测定评估了 CSCC 细胞的增殖、迁移和侵袭。我们的数据证实 miR-125a 在 CSCC 组织和细胞中的表达水平较低。功能上,miR-125a 的过表达极大地阻止了 CSCC 细胞的增殖、迁移和侵袭,而 miR-125a 表达的抑制则强烈增强了 CSCC 细胞的这些行为。此外,miR-125a 靶基因 Rad51 的表达极大地逆转了 miR-125a 介导的 CSCC 细胞增殖、迁移和侵袭的抑制。此外,我们发现 miR-125a 通过 Rad51 在 CSCC 细胞中下调了磷酸化 PI3K、AKT 和 mTOR 的水平。miR-125a 作为一种肿瘤抑制因子,可以通过靶向 Rad51 来减弱 CSCC 细胞的恶性行为。因此,miR-125a/Rad51 轴可能是 CSCC 治疗的一个靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2439/9161904/8ba4efed686c/KBIE_A_2051827_UF0001_OC.jpg

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