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Digestive Diseases and Sciences
Published in: Digestive Diseases and Sciences 4/2016

01-04-2016 | Original Article

Cytoplasmic Drosha Is Aberrant in Precancerous Lesions of Gastric Carcinoma and Its Loss Predicts Worse Outcome for Gastric Cancer Patients

Authors: Hailong Zhang, Yixuan Hou, Liyun Xu, Zongyue Zeng, Siyang Wen, Yan-e Du, Kexin Sun, Jiali Yin, Lei Lang, Xiaoli Tang, Manran Liu

Published in: Digestive Diseases and Sciences | Issue 4/2016

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Abstract

Background

The nuclear localization of Drosha is critical for its function as a microRNA maturation regulator. Dephosphorylation of Drosha at serine 300 and serine 302 disrupts its nuclear localization, and aberrant distribution of Drosha has been detected in some tumors.

Aims

The purpose of the present study was to assess cytoplasmic/nuclear Drosha expression in gastric cancer carcinogenesis and progression.

Methods

Drosha expression and its subcellular location was investigated by immunohistochemical staining of a set of tissue microarrays composed of normal adjacent tissues (374), chronic gastritis (137), precancerous lesions (94), and gastric adenocarcinoma (829) samples, and in gastric cancer cell lines with varying differentiation by immunofluorescence and western blot assay.

Results

Gradual loss of cytoplasmic Drosha was accompanied by tumor progression in both gastric cancer tissues and cell lines, and was inversely associated with tumor volume (P = 0.002), tumor grade (P < 0.001), tumor stage (P = 0.018), and distant metastasis (P = 0.026). Aberrant high levels of cytoplasmic Drosha were apparent in intestinal metaplasia and dysplasia tissues. The levels of nuclear Drosha were sharply decreased in chronic gastritis and maintained through precancerous lesions to gastric cancer. High levels of cytoplasmic Drosha predicted longer survival (LR = 7.088, P = 0.008) in gastric cancer patients.

Conclusions

Our data provide novel insights into gastric cancer that cytoplasmic Drosha potentially plays a role in preventing carcinogenesis and tumor progression, and may be an independent predictor of patient outcome.
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Metadata
Title
Cytoplasmic Drosha Is Aberrant in Precancerous Lesions of Gastric Carcinoma and Its Loss Predicts Worse Outcome for Gastric Cancer Patients
Authors
Hailong Zhang
Yixuan Hou
Liyun Xu
Zongyue Zeng
Siyang Wen
Yan-e Du
Kexin Sun
Jiali Yin
Lei Lang
Xiaoli Tang
Manran Liu
Publication date
01-04-2016
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 4/2016
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-015-3986-0

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