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MiR-182的下调通过调节TIAM1的表达与骨肉瘤细胞的生长和侵袭相关。

The Downregulation of MiR-182 Is Associated with the Growth and Invasion of Osteosarcoma Cells through the Regulation of TIAM1 Expression.

作者信息

Hu Jun, Lv Guohua, Zhou Shuguang, Zhou Yucheng, Nie Bangxu, Duan Hong, Zhang Yunfeng, Yuan Xiaofeng

机构信息

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China; Department of Orthopedics, The First Hospital of Kunming, Kunming, Yunnan, China.

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

出版信息

PLoS One. 2015 May 14;10(5):e0121175. doi: 10.1371/journal.pone.0121175. eCollection 2015.

Abstract

BACKGROUND

Osteosarcoma is the most common primary bone malignancy in children and young adults. Increasing results suggest that discovery of microRNAs (miRNAs) might provide a novel therapeutical target for osteosarcoma.

METHODS

MiR-182 expression level in osteosarcoma cell lines and tissues were assayed by qRT-PCR. MiRNA mimics or inhibitor were transfected for up-regulation or down-regulation of miR-182 expression. Cell function was assayed by CCK8, migration assay and invasion assay. The target genes of miR-182 were predicated by bioinformatics algorithm (TargetScan Human).

RESULTS

MiR-182 was down-regulated in osteosarcoma tissues and cell lines. Overexpression of miR-182 inhibited tumor growth, migration and invasion. Subsequent investigation revealed that TIAM1 was a direct and functional target of miR-182 in osteosarcoma cells. Overexpression of miR-182 impaired TIAM1-induced inhibition of proliferation and invasion in osteosarcoma cells.

CONCLUSIONS

Down-expression of miR-182 in osteosarcoma promoted tumor growth, migration and invasion by targeting TIAM1. MiR-182 might act as a tumor suppressor gene whose down-regulation contributes to the progression and metastasis of osteosarcoma, providing a potential therapy target for osteosarcoma patients.

摘要

背景

骨肉瘤是儿童和年轻成年人中最常见的原发性骨恶性肿瘤。越来越多的研究结果表明,微小RNA(miRNA)的发现可能为骨肉瘤提供一种新的治疗靶点。

方法

采用qRT-PCR检测骨肉瘤细胞系和组织中miR-182的表达水平。转染miRNA模拟物或抑制剂以上调或下调miR-182的表达。通过CCK8、迁移实验和侵袭实验检测细胞功能。通过生物信息学算法(TargetScan Human)预测miR-182的靶基因。

结果

miR-182在骨肉瘤组织和细胞系中表达下调。miR-182的过表达抑制肿瘤生长、迁移和侵袭。后续研究表明,TIAM1是骨肉瘤细胞中miR-182的直接功能靶点。miR-182的过表达削弱了TIAM1诱导的骨肉瘤细胞增殖和侵袭抑制。

结论

骨肉瘤中miR-182的低表达通过靶向TIAM1促进肿瘤生长、迁移和侵袭。miR-182可能作为一种肿瘤抑制基因,其下调促进骨肉瘤的进展和转移,为骨肉瘤患者提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8bd/4431740/c9077eb56988/pone.0121175.g001.jpg

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