Ino80 promotes cervical cancer tumorigenesis by activating Nanog expression.
Ino80 promotes cervical cancer tumorigenesis by activating Nanog expression.
复制标题
Ino80通过激活Nanog表达促进宫颈癌肿瘤发生。
DOI：
10.18632/oncotarget.12667
复制
发表时间：
2016-11-01
期刊：
影响因子：
--
通讯作者：
Song L
中科院分区：
文献类型：
--
作者：
Hu J;Liu J;Chen A;Lyu J;Ai G;Zeng Q;Sun Y;Chen C;Wang J;Qiu J;Wu Y;Cheng J;Shi X;Song L
Ino80 ATPase 是 INO80 ATP 依赖性染色质重塑复合物的组成部分，可调节转录、DNA 修复和复制。我们发现 Ino80 在宫颈癌细胞系和肿瘤样本中高表达。 Ino80 敲低可抑制宫颈癌细胞增殖，在体外诱导 G0/G1 期细胞周期停滞，并在体内抑制肿瘤生长。然而，Ino80敲低并不影响体外细胞的凋亡、迁移或侵袭。 Ino80 过表达促进了 H8 永生化宫颈上皮细胞系的增殖，与宫颈癌细胞系相比，该细胞系具有较低的内源性 Ino80 表达。 Ino80 与 Nanog 转录起始位点 (TSS) 结合并增强其在宫颈癌细胞中的表达。 Nanog 在 Ino80 敲低细胞系中的过度表达促进了细胞增殖。该研究首次证明Ino80在宫颈癌中表达上调，促进细胞增殖和肿瘤发生。我们的研究结果表明 Ino80 可能是治疗宫颈癌的潜在治疗靶点。
Ino80 ATPase is an integral component of the INO80 ATP-dependent chromatin-remodeling complex, which regulates transcription, DNA repair and replication. We found that Ino80 was highly expressed in cervical cancer cell lines and tumor samples. Ino80 knockdown inhibited cervical cancer cell proliferation, induced G0/G1 phase cell cycle arrest in vitro and suppressed tumor growth in vivo. However, Ino80 knockdown did not affect cell apoptosis, migration or invasion in vitro. Ino80 overexpression promoted proliferation in the H8 immortalized cervical epithelial cell line, which has low endogenous Ino80 expression as compared to cervical cancer cell lines. Ino80 bound to the Nanog transcription start site (TSS) and enhanced its expression in cervical cancer cells. Nanog overexpression in Ino80 knockdown cell lines promoted cell proliferation. This study demonstrated for the first time that Ino80 was upregulated in cervical cancer and promoted cell proliferation and tumorigenesis. Our findings suggest that Ino80 may be a potential therapeutic target for the treatment of cervical cancer.