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微小 RNA-330-5p 通过靶向原癌基因生存素抑制骨肉瘤细胞的生长和侵袭。

MicroRNA‑330‑5p inhibits osteosarcoma cell growth and invasion by targeting the proto‑oncogene survivin.

机构信息

Department of Traumatic Orthopaedics, Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui 230000, P.R. China.

Department of Traumatic Orthopaedics, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Hefei, Anhui 230000, P.R. China.

出版信息

Mol Med Rep. 2019 Sep;20(3):2236-2244. doi: 10.3892/mmr.2019.10447. Epub 2019 Jul 1.

Abstract

Increasing evidence has suggested the crucial role of the dysregulation of microRNAs (miRNAs) in osteosarcoma (OS) progression. MicroRNA (miR)‑330‑5p has been reported to exert tumor suppressive effects in various types of human cancer. However, the role of miR‑330‑5p in the development of OS and the underlying mechanism remain to be clarified. In the present study, miR‑330‑5p expression was found to be significantly decreased in OS tissues and cell lines. In addition, low miR‑330‑5p expression was highly correlated with the overall survival and clinical stage of OS. Overexpression of miR‑330‑5p inhibited the viability, migration and invasion, and promoted the apoptosis of OS cells, as well as induced cell cycle arrest at the G2/M phase. Subsequently, the proto‑oncogene survivin was identified as a functional target of miR‑330‑5p, and this was validated using a luciferase reporter assay. It was also demonstrated that survivin expression was markedly increased in OS tissues, and that it was negatively correlated with the expression of miR‑330‑5p. Furthermore, overexpression of survivin significantly abrogated the tumor‑suppressive effect induced by miR‑330‑5p on OS cells. In conclusion, these results revealed that the miR‑330‑5p/survivin axis has a significant tumor‑suppressive effect on OS, and may serve as a diagnostic and therapeutic target for the treatment of OS.

摘要

越来越多的证据表明,微小 RNA(miRNA)的失调在骨肉瘤(OS)进展中起着关键作用。已经有报道称,miRNA(miR)-330-5p 在多种人类癌症中发挥肿瘤抑制作用。然而,miR-330-5p 在 OS 发展中的作用及其潜在机制仍需阐明。在本研究中,发现 miR-330-5p 在 OS 组织和细胞系中的表达显著降低。此外,miR-330-5p 低表达与 OS 的总生存率和临床分期高度相关。miR-330-5p 的过表达抑制了 OS 细胞的活力、迁移和侵袭,并促进了细胞凋亡,同时诱导细胞周期停滞在 G2/M 期。随后,原癌基因 survivin 被鉴定为 miR-330-5p 的功能性靶标,并通过荧光素酶报告基因检测进行了验证。研究还表明,survivin 在 OS 组织中表达明显增加,并且与 miR-330-5p 的表达呈负相关。此外,survivin 的过表达显著削弱了 miR-330-5p 对 OS 细胞的肿瘤抑制作用。综上所述,这些结果表明,miR-330-5p/survivin 轴对 OS 具有显著的肿瘤抑制作用,可能作为 OS 治疗的诊断和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9392/6691255/a97c8c97fa15/MMR-20-03-2236-g00.jpg

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