Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma

Abstract

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.

STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma

“…[6][7][8][9] Sustained proliferation is a hallmark of transformed cells. Knockdown of BIC in malignant MyLa2059 cells entailed a 40% decrease of miR-155 expression (Fig.…”

“…It has been found overexpressed in hematological 4,5 as well as a number of solid cancers. [6][7][8][9] miR-155 is localized within an exon of its precursor gene BIC (B cell integration cluster or pri-miR-155). 4 Transiently elevated expression of miR-155 plays a role in the activation of several types of immune cells, 2,[10][11][12] whereas constitutively high levels of this miRNA can result in the development of malignancies by increase of genomic instability 13,14 and sustained proliferation and survival 5,15 of malignant cells.…”

Integrated microRNA-mRNA analysis of pancreatic ductal adenocarcinoma

“…Recent studies have focused on miRNA expression profiling of pancreatic adenocarcinoma. Aberrant expression of miRNA, such as miR-21 and miR-155, in the pancreas, often contributes to cancer development and invasion (Giovannetti et al, 2010;Ryu et al, 2010). On the other hand, miRNA such as miR-34 and miR-150 may also suppress the growth and malignant behavior of pancreatic cancer cells (Liu et al, 2011;Srivastava et al, 2011).…”

Monitoring microRNAs Using a Molecular Beacon in CD133+/CD338+Human Lung Adenocarcinoma-initiating A549 Cells

“…miR-155 plays an important role in various physiological and pathological processes (Faraoni et al, 2009;Elton et al, 2012) and has been found to be upregulated in several solid tumors, such as clear-cell kidney cancer (Juan et al, 2010), hepatocellular carcinoma (Wang et al, 2009a), breast cancer (Jiang et al, 2010;Kong et al, 2010), pancreatic cancer (Habbe et al, 2009;Greither et al, 2010;Ryu et al, 2010), and lung cancer (Yanaihara et al, 2006;Donnem et al, 2011). Moreover, high miR-155 expression is associated with a poor prognosis in lung cancer (Yanaihara et al, 2006;Donnem et al, 2011), suggesting that elevated miR-155 expression might be a prognostic biomarker of lung cancer (Xie et al, 2010).…”