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LAMP3 在骨肉瘤细胞中发挥致癌作用,部分是通过抑制 TP53。

LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53.

机构信息

1Department of Bone Traumatology, Yantaishan Hospital, Yantai, 264000 Shandong Province People's Republic of China.

2Department of Spinal Research, Yantaishan Hospital, Yantai, 264000 Shandong Province People's Republic of China.

出版信息

Cell Mol Biol Lett. 2018 Jul 11;23:33. doi: 10.1186/s11658-018-0099-8. eCollection 2018.

Abstract

BACKGROUND

Osteosarcoma (OS) is a common malignant tumor that predominantly occurs in adolescents. Its most common metastasis is to the lungs. As shown in our earlier study, lysosome-associated membrane glycoprotein 3 (LAMP3) is highly upregulated in metastatic OS. However, its role in the regulation of OS cell viability and apoptosis remains unknown.

METHODS

We knocked down and overexpressed in OS cells and assessed the cell viability and apoptosis. Then, we investigated the expression of apoptosis-associated genes to identify the downstream gene(s) of .

RESULTS

Knockdown of significantly inhibited OS cell viability and promoted apoptosis. , which is involved in the apoptosis pathway, was found to be highly upregulated after knockdown of . Overexpression of significantly increased cell viability and abrogated apoptosis. Importantly, subsequent knockdown of partially suppressed the increased OS cell apoptosis induced by the inhibition of , suggesting that is a key functional downstream gene of .

CONCLUSIONS

Our findings suggest that promotes OS cell viability and survival by regulating expression.

摘要

背景

骨肉瘤(OS)是一种常见的恶性肿瘤,主要发生在青少年中。其最常见的转移部位是肺部。正如我们之前的研究所示,溶酶体相关膜糖蛋白 3(LAMP3)在转移性 OS 中高度上调。然而,其在调节 OS 细胞活力和凋亡中的作用尚不清楚。

方法

我们在 OS 细胞中敲低和过表达 ,并评估细胞活力和凋亡。然后,我们研究了凋亡相关基因的表达,以确定 的下游基因(多个)。

结果

敲低 显著抑制 OS 细胞活力并促进凋亡。 在敲低 后被发现高度上调,其参与凋亡途径。 过表达显著增加细胞活力并消除凋亡。重要的是,随后敲低 部分抑制了由抑制 引起的 OS 细胞凋亡的增加,表明 是 的关键功能下游基因。

结论

我们的研究结果表明, 通过调节 表达促进 OS 细胞活力和存活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb38/6042264/2aa63c488f9d/11658_2018_99_Fig1_HTML.jpg

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