Ma Chenchao, Nong Kate, Zhu Hongda, Wang Weiwei, Huang Xinyu, Yuan Zhou, Ai Kaixing
Department of General Surgery, The Sixth People' Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
Tumour Biol. 2014 Sep;35(9):9163-9. doi: 10.1007/s13277-014-2185-5. Epub 2014 Jun 12.
The long noncoding RNA (lncRNA) H19 has been recently characterized as an oncogenic lncRNA in some tumors. However, the role of H19 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, we found that not only the levels of H19 was overexpressed in PDAC compared with adjacent normal tissues, but also H19 expression was upregulated remarkably in primary tumors which subsequently metastasized, compared to those did not metastasis. Subsequently, the efficacy of knockdown of H19 by H19-small interfering RNA (siRNA) was evaluated in vitro, and we found that downregulation of H19 impaired PDAC cell invasion and migration. We further demonstrated that H19 promoted PDAC cell invasion and migration at least partially by increasing HMGA2-mediated epithelial-mesenchymal transition (EMT) through antagonizing let-7. This study suggests an important role of H19 in regulating metastasis of PDAC and provides some clues for elucidating the lncRNA-miRNA functional network in cancer.
长链非编码RNA（lncRNA）H19最近在一些肿瘤中被鉴定为一种致癌lncRNA。然而，H19在胰腺导管腺癌（PDAC）中的作用仍不清楚。在本研究中，我们发现，与邻近正常组织相比，H19不仅在PDAC中表达上调，而且在随后发生转移的原发性肿瘤中，H19的表达相较于未发生转移的肿瘤显著上调。随后，我们在体外评估了H19小干扰RNA（siRNA）敲低H19的效果，发现H19表达下调会损害PDAC细胞的侵袭和迁移能力。我们进一步证明，H19至少部分地通过拮抗let-7增加HMGA2介导的上皮-间质转化（EMT）来促进PDAC细胞的侵袭和迁移。本研究表明H19在调节PDAC转移中起重要作用，并为阐明癌症中的lncRNA- miRNA功能网络提供了一些线索。
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