Abstract
Background:Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis. However, the clinical significance of Lin28 expression in oesophageal cancer has not been elucidated.Methods:Lin28 and Lin28B expression was examined by immunohistochemistry in 161 tissues from patients with oesophageal cancer who had undergone curative surgery. The relationship between the expressions of Lin28 and Lin28B and various clinicopathological factors was examined. In vitro assays were conducted to determine the role of Lin28 in aggressiveness of oesophageal cancers using oesophageal cancer cell line.Results:Lin28 and Lin28B were overexpressed in oesophageal cancer cells compared with non-cancerous epithelial cells, especially in the invasive front. High expression of Lin28 and Lin28B correlated significantly with lymph node metastasis and poor prognosis. High expression of Lin28B expression correlated significantly with low expression of let-7. Multivariate analysis also identified Lin28B expression as an independent prognostic factor. In vitro assays showed that the proliferative and invasive activities were significantly reduced in Lin28B-knockdown cells, compared with control cells.Conclusion:High expression of Lin28 is associated with poor prognosis and high tumour aggressiveness in oesophageal cancer and these effects are mediated through increased proliferation and invasiveness of oesophageal cancer cells.
Highlights
Lin28 is a negative regulator of the tumour suppressor microRNA, let-7, suggesting its role in tumourigenesis
Lin28 is a negative regulator of let-7 family, which may act as a tumour suppressor miRNA, suggesting that Lin28 could contribute to tumourigenesis
The present study demonstrated that high expression of Lin28 and Lin28B is associated with lymph node metastasis and poor prognosis of patients with oesophageal cancers
Summary
R Hamano, H Miyata*,1, M Yamasaki, K Sugimura, K Tanaka, Y Kurokawa, K Nakajima, S Takiguchi, Y Fujiwara, M Mori and Y Doki1 1Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Yamadaoka 2-2, Osaka 565-0871, Japan
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