HOTTIP and HOXA13 are oncogenes associated with gastric cancer progression
HOTTIP and HOXA13 are oncogenes associated with gastric cancer progression
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HOTTIP 和 HOXA13 是与胃癌进展相关的癌基因
DOI：
10.3892/or.2016.4743
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发表时间：
2016-06-01
期刊：
影响因子：
4.2
通讯作者：
Che, Xiangming
中科院分区：
文献类型：
--
作者：
Chang, Shuai;Liu, Junsong;Che, Xiangming
名为 HOTTIP（远端 HOXA 转录物）的长非编码 RNA 协调各种 5' HOXA 基因的激活，这些基因通过靶向 WDR5/MLL 复合物编码发育的主调节因子。 HOTTIP 在多种癌症中充当癌基因，但其在胃癌中的生物学功能从未被研究过。在本研究中，我们研究了 HOTTIP 在胃癌中的作用。我们发现 HOTTIP 在胃癌细胞系中表达上调。敲除胃癌细胞中的 HOTTIP 可抑制细胞增殖、迁移和侵袭。此外，HOTTIP 的下调导致胃癌细胞系中同源盒蛋白 Hox-A13 (HOXA13) 的表达减少。 HOXA13 参与 HOTTIP 诱导的胃癌细胞恶性表型。我们的数据显示，与非肿瘤组织中的对应物相比，胃癌组织中 HOTTIP 和 HOXA13 的水平均显着上调。此外，HOTTIP和HOXA13在低分化、TNM分期晚期、有淋巴结转移的胃癌中表达水平较高。 Spearman分析表明HOTTIP和HOXA13在非肿瘤粘膜和癌症病变中均呈高度正相关。总的来说，这些发现表明 HOTTIP 和 HOXA13 在胃癌进展中发挥重要作用，并为该疾病的治疗提供了新的见解。
A long non-coding RNA named HOTTIP (HOXA transcript at the distal tip) coordinates the activation of various 5' HOXA genes which encode master regulators of development through targeting the WDR5/MLL complex. HOTTIP acts as an oncogene in several types of cancers, whereas its biological function in gastric cancer has never been studied. In the present study, we investigated the role of HOTTIP in gastric cancer. We found that HOTTIP was upregulated in gastric cancer cell lines. Knockdown of HOTTIP in gastric cancer cells inhibited cell proliferation, migration and invasion. Moreover, downregulation of HOTTIP led to decreased expression of homeobox protein Hox-A13 (HOXA13) in gastric cancer cell lines. HOXA13 was involved in HOTTIP-induced malignant phenotypes of gastric cancer cells. Our data showed that the levels of HOTTIP and HOXA13 were both markedly upregulated in gastric cancer tissues compared with their counterparts in non-tumorous tissues. Furthermore, the expression levels of HOTTIP and HOXA13 were both higher in gastric cancer which was poorly differentiated, at advanced TNM stages and exhibited lymph node-metastasis. Spearman analyses indicated that HOTTIP and HOXA13 had a highly positive correlation both in non-tumor mucosae and cancer lesions. Collectively, these findings suggest that HOTTIP and HOXA13 play important roles in gastric cancer progression and provide a new insight into therapeutic treatment for the disease.