miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma.
miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma.
复制标题
miR-145 通过靶向高级别浆液性卵巢癌中的metadherin 抑制肿瘤生长和转移。
DOI：
10.18632/oncotarget.2522
复制
发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Kong B
中科院分区：
文献类型：
--
作者：
Dong R;Liu X;Zhang Q;Jiang Z;Li Y;Wei Y;Li Y;Yang Q;Liu J;Wei JJ;Shao C;Liu Z;Kong B
高级别浆液性卵巢癌（HGSOC）是最常见和最具侵袭性的上皮性卵巢癌亚型，其特征在于TP 53突变和遗传不稳定性。使用miRNA谱分析，我们发现miR-145（一种p53调节的miRNA）在HGSOC中经常下调。通过qPCR在大的HGSOC队列中进一步验证了miR-145下调。miR-145在卵巢癌细胞中的过表达在体外显著抑制细胞的增殖、迁移和侵袭，在体内显著抑制肿瘤的生长和转移。Metadherin（MTDH）随后被鉴定为miR-145的直接靶标，并且发现在HGSOC中显著上调。此外，MTDH的过表达挽救了卵巢癌细胞中miR-145的抑制作用。最后，我们发现MTDH的高表达水平与HGSOC的不良预后相关。因此，当p53功能障碍时，miR-145对MTDH的抑制缺乏导致HGSOC的肿瘤生长和转移增加。我们的研究建立了p53、miR-145和MTDH在HGSOC中调节肿瘤生长和转移的新联系。
High-grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of epithelial ovarian cancer, is characterized by TP53 mutations and genetic instability. Using miRNA profiling analysis, we found that miR-145, a p53 regulated miRNA, was frequently down-regulated in HGSOC. miR-145 down-regulation was further validated in a large cohort of HGSOCs by qPCR. Overexpression of miR-145 in ovarian cancer cells significantly suppressed proliferation, migration and invasion in vitro and inhibited tumor growth and metastasis in vivo. Metadherin (MTDH) was subsequently identified as a direct target of miR-145, and was found to be significantly up-regulated in HGSOC. Furthermore, overexpression of MTDH rescued the inhibitory effects of miR-145 in ovarian cancer cells. Finally, we found that high level of MTDH expression correlated with poor prognosis of HGSOC. Therefore, lack of suppression of MTDH by miR-145 when p53 is dysfunctional leads to increased tumor growth and metastasis of HGSOC. Our study established a new link between p53, miR-145 and MTDH in the regulation of tumor growth and metastasis in HGSOC.
登录
查看更多内容
影响因子：
50.3
作者：
Hu G;Chong RA;Yang Q;Wei Y;Blanco MA;Li F;Reiss M;Au JL;Haffty BG;Kang Y
通讯作者：
Kang Y
影响因子：
--
作者：
Emdad, Luni;Das, Swadesh K.;Dasgupta, Santanu;Hu, Bin;Sarkar, Devanand;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
DOI：
10.1038/nrc3144
发表时间：
2011-09-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Wan L;Lu X;Yuan S;Wei Y;Guo F;Shen M;Yuan M;Chakrabarti R;Hua Y;Smith HA;Blanco MA;Chekmareva M;Wu H;Bronson RT;Haffty BG;Xing Y;Kang Y
通讯作者：
Kang Y