TMED3/RPS15A Axis promotes the development and progression of osteosarcoma.
TMED3/RPS15A Axis promotes the development and progression of osteosarcoma.
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TMED3/RPS15A Axis促进骨肉瘤的发生和进展
DOI：
10.1186/s12935-021-02340-w
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发表时间：
2021-11-27
影响因子：
5.8
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Xu W;Li Y;Ye X;Ji Y;Chen Y;Zhang X;Li Z
骨肉瘤是一种主要影响儿童和年轻人的原发性恶性肿瘤。跨膜 emp24 运输蛋白 3 (TMED3) 可能参与恶性癌症行为的调节。然而，TMED3 在骨肉瘤中的作用仍然是个谜。本研究阐述了TMED3在骨肉瘤进展中的潜在生物学功能和潜在机制。通过免疫组织化学染色分析骨肉瘤中TMED3的表达。通过体外功能丧失测定确定了 TMED3 在骨肉瘤中的生物学功能。通过异种移植肿瘤模型进一步探讨TMED3下调对骨肉瘤的影响。通过基因表达谱分析确定TMED3调控骨肉瘤的分子机制。骨肉瘤组织中TMED3的表达显着高于相匹配的癌旁正常组织。 TMED3 的敲低通过抑制增殖、阻碍迁移和增强体外细胞凋亡来抑制骨肉瘤的进展。我们进一步验证了 TMED3 的敲低可抑制体内骨肉瘤的产生。此外，核糖体蛋白 S15A (RPS15A) 被确定为 TMED3 参与骨肉瘤进展的潜在下游靶标。进一步的研究表明，同时敲低 RPS15A 和 TMED3 增强了对骨肉瘤细胞的抑制作用。重要的是，RPS15A 的敲低减轻了骨肉瘤细胞中 TMED3 过表达的促进作用。总之，这些发现强调了 TMED3/RPS15A 轴在促进肿瘤进展中的重要性，这可能是骨肉瘤分子治疗的有希望的候选者。在线版本包含可在 10.1186/s12935-021-02340-w 获取的补充材料。
Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated. The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis. The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells. In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma. The online version contains supplementary material available at 10.1186/s12935-021-02340-w.
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影响因子：
28.2
作者：
Sayles LC;Breese MR;Koehne AL;Leung SG;Lee AG;Liu HY;Spillinger A;Shah AT;Tanasa B;Straessler K;Hazard FK;Spunt SL;Marina N;Kim GE;Cho SJ;Avedian RS;Mohler DG;Kim MO;DuBois SG;Hawkins DS;Sweet-Cordero EA
通讯作者：
Sweet-Cordero EA
影响因子：
4.8
作者：
Luo, Weibo;Wang, Yingfei;Reiser, Georg
通讯作者：
Reiser, Georg
影响因子：
3.8
作者：
Oshima, K;Yanase, N;Mizuguchi, J
通讯作者：
Mizuguchi, J
影响因子：
2
作者：
Jiménez, L;Becerra, A;Landa, A
通讯作者：
Landa, A
影响因子：
4
作者：
Ng, Victoria H.;Hang, Brian I.;Lee, Ethan
通讯作者：
Lee, Ethan