Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
Department of Endoscopy, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130031, P.R. China.
Oncol Rep. 2018 Apr;39(4):1591-1600. doi: 10.3892/or.2018.6245. Epub 2018 Feb 2.
Long non-coding RNAs (lncRNAs) have been implicated in the occurrence and progression of multiple cancers. In the present study, we investigated the role of lncRNA X inactive-specific transcript (XIST) in the development and progression of pancreatic cancer (PC). Firstly, we found that lncRNA XIST was markedly upregulated in PC tissues and PC cell lines, respectively. Overexpression of XIST significantly promoted the proliferation, migration and invasion, and suppressed cell apoptosis of BxPC-3 cells; knockdown of XIST significantly inhibited the proliferation, migration and invasion, and accelerated cell apoptosis of PANC-1 cells. Furthermore, BxPC-3 and PANC-1 cells transfected with different vectors were injected subcutaneously into nude mice to explore tumor formation. We found that XIST promoted tumor formation in vivo. Subsequently, we found that microRNA-34a-5p (miR‑34a-5p) was downregulated in PC tissues, and predicted a poor prognosis in PC patients. In addition, the results indicated that miR-34a-5p is a target gene of XIST and was significantly negatively correlated with XIST. More importantly, we found that miR-34a-5p rescued the facilitation of malignant behavior mediated by XIST. These results indicated that XIST and miR-34a-5p may be potential effective therapeutic targets for PC.
长链非编码 RNA（lncRNA）与多种癌症的发生和发展有关。在本研究中，我们研究了 lncRNA X 失活特异性转录物（XIST）在胰腺癌（PC）发展和进展中的作用。首先，我们发现 lncRNA XIST 在 PC 组织和 PC 细胞系中均明显上调。XIST 的过表达显著促进了 BxPC-3 细胞的增殖、迁移和侵袭，同时抑制了细胞凋亡；而 XIST 的敲低则显著抑制了 PANC-1 细胞的增殖、迁移和侵袭，同时加速了细胞凋亡。此外，将不同载体转染的 BxPC-3 和 PANC-1 细胞分别注射到裸鼠皮下以探讨肿瘤形成。我们发现 XIST 促进了体内肿瘤的形成。随后，我们发现 miR-34a-5p（miR-34a-5p）在 PC 组织中下调，并预测了 PC 患者的预后不良。此外，结果表明 miR-34a-5p 是 XIST 的靶基因，与 XIST 呈显著负相关。更重要的是，我们发现 miR-34a-5p 挽救了 XIST 介导的恶性行为的促进作用。这些结果表明，XIST 和 miR-34a-5p 可能是 PC 的潜在有效治疗靶点。
