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长链非编码 RNA MEG3 作为一种肿瘤抑制因子,在人类胰腺癌中具有预后预测价值。

Long non-coding RNA MEG3 functions as a tumour suppressor and has prognostic predictive value in human pancreatic cancer.

机构信息

Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.

Clinic of General, Visceral and Transplantation Surgery, University of Ulm, D-89081 Ulm, Germany.

出版信息

Oncol Rep. 2018 Mar;39(3):1132-1140. doi: 10.3892/or.2018.6178. Epub 2018 Jan 2.

DOI:10.3892/or.2018.6178
PMID:29328401
Abstract

Long non-coding RNA (lncRNA) MEG3 has been demonstrated to be a tumour suppressor in many malignancies. However, the functional role of MEG3 in pancreatic cancer (PC) is unclear. In this study, the expression pattern of MEG3 was evaluated in 25 samples of microdissected PC tissues and 8 PC cell lines and was compared to the expression in adjacent non‑cancerous tissues and a human pancreatic normal epithelial cell line. Loss of MEG3 expression was observed in both the cancerous tissues and cancer cell lines. Although the absence of expression of MEG3 was not statistically correlated to either histological grade or TNM stage in the 25 cases, the prognosis was significantly worse. MEG3 knockdown enhanced cell proliferation, promoted cell migration and invasion, induced epithelial‑mesenchymal transition (EMT), increased the sphere‑forming ability and cancer stem cell (CSC) properties, and decreased the chemosensitivity to gemcitabine in vitro. In contrast, forced expression of MEG3 resulted in a reverse effect. In conclusion, MEG3 functions as a tumour suppressor in human PC. The underlying cause of the poor prognosis induced by low levels of MEG3 expression in PC patients might involve EMT induction, enhanced CSC phenotypes and reduced chemoresistance, all of which might be associated with Snail activation.

摘要

长链非编码 RNA(lncRNA)MEG3 在许多恶性肿瘤中被证实是一种肿瘤抑制因子。然而,MEG3 在胰腺癌(PC)中的功能作用尚不清楚。在这项研究中,评估了 MEG3 在 25 个微切割 PC 组织样本和 8 个 PC 细胞系中的表达模式,并与相邻非癌组织和人胰腺正常上皮细胞系中的表达进行了比较。在癌组织和癌细胞系中均观察到 MEG3 表达缺失。尽管在 25 例中,MEG3 表达缺失与组织学分级或 TNM 分期均无统计学相关性,但预后明显较差。MEG3 敲低增强了细胞增殖,促进了细胞迁移和侵袭,诱导了上皮-间充质转化(EMT),增加了球体形成能力和癌症干细胞(CSC)特性,并降低了体外对吉西他滨的化疗敏感性。相反,强制表达 MEG3 则产生了相反的效果。总之,MEG3 在人 PC 中作为肿瘤抑制因子发挥作用。PC 患者 MEG3 表达水平低导致预后不良的潜在原因可能涉及 EMT 诱导、增强的 CSC 表型和降低的化疗耐药性,所有这些都可能与 Snail 激活有关。

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