MicroRNA‑466 inhibits cell proliferation and invasion in osteosarcoma by directly targeting insulin receptor substrate 1

Sun,Yongning; Zhou,Jingzhen; Shi,Lina; Li,Jie; Chen,Jianming

doi:10.3892/mmr.2019.9956

MicroRNA‑466 inhibits cell proliferation and invasion in osteosarcoma by directly targeting insulin receptor substrate 1

Authors:
- Yongning Sun
- Jingzhen Zhou
- Lina Shi
- Jie Li
- Jianming Chen
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Affiliations: Department of Clinical Laboratory, Ningbo No. 6 Hospital, Ningbo, Zhejiang 315040, P.R. China, Department of Emergency, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315040, P.R. China, Department of Orthopedics, Ningbo No. 6 Hospital, Ningbo, Zhejiang 315040, P.R. China
Published online on: February 14, 2019 https://doi.org/10.3892/mmr.2019.9956
Pages: 3345-3352

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Abstract

Accumulating evidence has demonstrated that microRNAs (miRNAs) are frequently dysregulated in osteosarcoma (OS), and the aberrant expression of miRNAs is associated with OS initiation and progression. Previous studies demonstrated that miRNA‑466 (miR‑466) is dysregulated, and serves important roles in various types of human cancer. However, the role of miR‑466 in the formation and progression of OS remains unclear. In the present study, the expression level of miR‑466 was identified to be markedly downregulated in OS tissues and cell lines. Additionally, miR‑466 overexpression inhibited the proliferative and invasive abilities of OS cells. In the present study, bioinformatics analyses and luciferase assays were employed to show that miR‑466 was able to directly target the 3'‑untranslated region of insulin receptor substrate 1 (IRS1) gene, negatively regulating the mRNA and the protein expression levels of IRS1 in OS cells. Furthermore, IRS1 was upregulated in OS tissues, and the increased expression level of IRS1 exhibited an inverse correlation with the expression level of miR‑466. Furthermore, IRS1 overexpression was able to partially reverse the suppressive effects of miR‑466 overexpression in OS cells. To the best of the authors' knowledge, the present study is the first to suggest that miR‑466 is downregulated in OS and inhibits the progression of OS by directly targeting IRS1. The present results suggested that miR‑466 may represent a novel potential therapeutic target for the treatment of patients with OS.

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