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miR-181a-5p 通过 PTEN/AKT 通路促进骨肉瘤进展。

MicroRNA-181a-5p Promotes Osteosarcoma Progression via PTEN/AKT Pathway.

机构信息

Department of Orthopedic Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

出版信息

Anal Cell Pathol (Amst). 2022 Mar 8;2022:3421600. doi: 10.1155/2022/3421600. eCollection 2022.

Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with poor prognosis. MicroRNA-181a-5p (miR-181a-5p) is involved in the progression of various tumors; however, its role and underlying mechanism in osteosarcoma remains unclear. In this study, we found that miR-181a-5p was upregulated in human osteosarcoma cells and tissues. miR-181a-5p mimic significantly promoted, while miR-181a-5p inhibitor blocked the proliferation, colony formation, migration, invasion, and cell cycle progression of osteosarcoma cells. Mechanistically, miR-181a-5p bound to the 3'-untranslational region of phosphatase and tensin homolog (PTEN) and reduced its protein expression, thereby activating protein kinase B (PKB/AKT) pathway. Either PTEN overexpression or AKT inhibition notably blocked the tumor-promoting effects of miR-181a-5p. Moreover, we observed that miR-181a-5p mimic further inhibited growth of human osteosarcoma cells in the presence of adriamycin or cisplatin. Overall, miR-181a-5p promotes osteosarcoma progression via PTEN/AKT pathway and it is a promising therapeutic target to treat osteosarcoma.

摘要

骨肉瘤是儿童和青少年中最常见的原发性恶性骨肿瘤,预后较差。microRNA-181a-5p(miR-181a-5p)参与多种肿瘤的进展;然而,其在骨肉瘤中的作用和潜在机制尚不清楚。在本研究中,我们发现 miR-181a-5p 在人骨肉瘤细胞和组织中上调。miR-181a-5p 模拟物显著促进,而 miR-181a-5p 抑制剂则阻断骨肉瘤细胞的增殖、集落形成、迁移、侵袭和细胞周期进程。在机制上,miR-181a-5p 与磷酸酶和张力蛋白同源物(PTEN)的 3'-非翻译区结合并降低其蛋白表达,从而激活蛋白激酶 B(PKB/AKT)途径。PTEN 过表达或 AKT 抑制均可显著阻断 miR-181a-5p 的促肿瘤作用。此外,我们观察到 miR-181a-5p 模拟物在阿霉素或顺铂存在的情况下进一步抑制人骨肉瘤细胞的生长。总体而言,miR-181a-5p 通过 PTEN/AKT 途径促进骨肉瘤进展,是治疗骨肉瘤的有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/95c4/8924609/a4cbc3fcfe67/ACP2022-3421600.001.jpg

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