Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells.
Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells.
复制标题
DOI：
10.18632/oncotarget.7020
复制
发表时间：
2016-03-01
期刊：
影响因子：
--
通讯作者：
Carrier F
中科院分区：
文献类型：
--
作者：
Chang ET;Parekh PR;Yang Q;Nguyen DM;Carrier F
异源核糖核蛋白A18(HnRNP A18)通过协调与增殖和生存相关的选定转录本的翻译而促进肿瘤生长。HnRNP A18与支持生存的基因的转录本结合并稳定，该转录本在其3‘UTRs中含有其RNA签名基序。HnRNPA18结合ATR、RPA、Trx、HIF-1α和多聚体上的几种蛋白质翻译因子mRNAs，促进细胞应激条件下的从头蛋白质翻译。最重要的是，在黑色素瘤和乳腺癌这两种小鼠异种移植模型中，hnRNP A18的下调不仅可以显著减少肿瘤的生长，还可以减少增殖、侵袭和迁移。此外，对人类黑色素瘤、前列腺癌、乳腺癌和结肠癌进行的组织微阵列显示，与正常邻近组织相比，hnRNP A18在这些恶性组织中过表达40%至60%。免疫组织化学数据显示，hnRNP A18在人类肿瘤的间质和缺氧区过表达。因此，这些数据表明，hnRNP A18可以通过协调支持生存的转录本的翻译来促进体内模型中的肿瘤生长，以支持增殖细胞的需求，并提高细胞应激下的存活率。因此，hnRNP A18代表了选择性抑制肿瘤细胞中蛋白质翻译的新靶点。
The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3′UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1α and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells.