异常表达的 microRNA-155 是胰腺导管腺癌多步骤进展过程中的早期事件。
Aberrant MicroRNA-155 expression is an early event in the multistep progression of pancreatic adenocarcinoma.
机构信息
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Baltimore, MD, USA.
出版信息
Pancreatology. 2010;10(1):66-73. doi: 10.1159/000231984. Epub 2010 Mar 20.
BACKGROUND/AIMS: Pancreatic intraepithelial neoplasia (PanIN) is the most common noninvasive precursor to invasive pancreatic adenocarcinoma. Misexpression of microRNAs (miRNAs) is commonly encountered in invasive neoplasia; however, miRNA abnormalities in PanIN lesions have not been documented.
METHODS
Three candidate miRNAs (miR-21, miR-155, and miR-221) previously reported as overexpressed in pancreatic cancers were assessed in 31 microdissected PanINs (14 PanIN-1, 9 PanIN-2, 8 PanIN-3) using quantitative reverse transcription PCR (qRT-PCR). Subsequently, miR-155 was evaluated by locked nucleic acid in situ hybridization (LNA-ISH) in PanIN tissue microarrays.
RESULTS
Relative to microdissected non-neoplastic ductal epithelium, significant overexpression of miR-155 was observed in both PanIN-2 (2.6-fold, p = 0.02) and in PanIN-3 (7.4-fold, p = 0.014), while borderline significant overexpression of miR-21 (2.5-fold, p = 0.049) was observed in PanIN-3 only. In contrast, no significant differences in miR-221 levels were observed between ductal epithelium and PanIN lesions by qRT-PCR. LNA-ISH confirmed the aberrant expression of miR-155 in PanIN-2 (9 of 20, 45%) and in PanIN-3 (8 of 13, 62%), respectively, when compared with normal ductal epithelium (0 of 10) (p < 0.01).
CONCLUSIONS
Abnormalities of miRNA expression are observed in the multistep progression of pancreatic cancer, with miR-155 aberrations demonstrable at the stage of PanIN-2, and miR-21 abnormalities at the stage of PanIN-3 lesions. and IAP.
背景/目的：胰腺上皮内瘤变（PanIN）是最常见的浸润性胰腺腺癌的非浸润性前体。微小 RNA（miRNA）的错误表达在侵袭性肿瘤中常见；然而，PanIN 病变中的 miRNA 异常尚未有文献记载。
方法
使用定量逆转录聚合酶链反应（qRT-PCR）在 31 个微切割的 PanIN （14 个 PanIN-1、9 个 PanIN-2、8 个 PanIN-3）中评估了 3 种候选 miRNA（miR-21、miR-155 和 miR-221），这些 miRNA 先前在胰腺癌中被报道过表达。随后，通过锁定核酸原位杂交（LNA-ISH）在 PanIN 组织微阵列中评估 miR-155。
结果
与微切割的非肿瘤性导管上皮相比，miR-155 在 PanIN-2（2.6 倍，p = 0.02）和 PanIN-3（7.4 倍，p = 0.014）中均有显著过表达，而 miR-21 （2.5 倍，p = 0.049）仅在 PanIN-3 中过表达。相比之下，qRT-PCR 显示 miR-221 在导管上皮和 PanIN 病变之间的水平无显著差异。LNA-ISH 证实 miR-155 在 PanIN-2（20 例中有 9 例，45%）和 PanIN-3（13 例中有 8 例，62%）中存在异常表达，与正常导管上皮（10 例中有 0 例）相比（p < 0.01）。
结论
miRNA 表达异常发生在胰腺癌的多步进展中，miR-155 异常可见于 PanIN-2 阶段，miR-21 异常可见于 PanIN-3 病变。
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