Department of Hepatobiliary-pancreatic and Integrative Oncology, Minhang Branch, Fudan University Shanghai Cancer Center, Shanghai, 200240, PR China.
Department of Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, PR China.
Int J Biochem Cell Biol. 2019 Aug;113:17-26. doi: 10.1016/j.biocel.2019.05.021. Epub 2019 Jun 1.
Pancreatic cancer (PC) has become a worldwide malignancy accompanied by high metastasis and extremely poor prognosis. The critical roles of long non-coding RNAs (lncRNAs) in PC are generally summarized as molecular sponges of microRNAs (miRNAs). We intended to investigate the biological function and mechanism of lncRNA X-inactive specific transcript (XIST) in PC progression, especially in PC cell migration and invasion. qPCR was applied to detect the expression levels of XIST and miR-429 in PC tissues and cell lines. The roles of XIST and miR-429 on PC cell migration, invasion and epithelial-mesenchymal transition (EMT) were assessed by wound healing, transwell, qPCR and Western blot assays, respectively. The regulating relationship among XIST, miR-429 and zinc finger E-box binding homeobox 1 (ZEB1) was investigated in PC cells. XIST was frequently upregulated while miR-429 was commonly downregulated in PC tissues, especially in metastatic PC tissues. Knockdown of XIST in two PC cell lines caused inhibition of migration, invasion and EMT capacities. Forced expression of miR-429 exerted the similar tumor suppressing effects. XIST repressed miR-429 expression thus upregulated ZEB1, one of the targets of miR-429. ZEB1 mediated the tumor suppressing roles of XIST knockdown in PC cells. We identified the critical axis of XIST/miR-429/ZEB1 in PC cell migration, invasion and EMT, which may aid in developing new therapeutic strategies for PC.
胰腺癌（PC）已成为一种全球性恶性肿瘤，具有高转移率和极差的预后。长链非编码 RNA（lncRNA）在 PC 中的关键作用通常概括为 microRNA（miRNA）的分子海绵。我们旨在研究 lncRNA X 失活特异性转录物（XIST）在 PC 进展中的生物学功能和机制，特别是在 PC 细胞迁移和侵袭中的作用。qPCR 用于检测 PC 组织和细胞系中 XIST 和 miR-429 的表达水平。通过划痕愈合、Transwell、qPCR 和 Western blot 测定分别评估 XIST 和 miR-429 对 PC 细胞迁移、侵袭和上皮-间充质转化（EMT）的作用。在 PC 细胞中研究了 XIST、miR-429 和锌指 E 框结合同源盒 1（ZEB1）之间的调节关系。XIST 在 PC 组织中频繁上调，而 miR-429 普遍下调，尤其是在转移性 PC 组织中。两种 PC 细胞系中 XIST 的敲低导致迁移、侵袭和 EMT 能力的抑制。miR-429 的强制表达产生了类似的肿瘤抑制作用。XIST 抑制 miR-429 的表达，从而上调 ZEB1，miR-429 的一个靶标。ZEB1 介导了 XIST 敲低在 PC 细胞中的肿瘤抑制作用。我们确定了 XIST/miR-429/ZEB1 在 PC 细胞迁移、侵袭和 EMT 中的关键轴，这可能有助于为 PC 开发新的治疗策略。
