Hailong Zhang1, Yixuan Hou2, Liyun Xu1, Zongyue Zeng1, Siyang Wen1, Yan-E Du1, Kexin Sun1, Jiali Yin1, Lei Lang1, Xiaoli Tang3, Manran Liu4. 1. Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. 2. Experimental Teaching Center of Basic Medicine Science, Chongqing Medical University, Chongqing, 400016, China. 3. Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA. 4. Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China. mliu-hncq@hotmail.com.
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.
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 cancerpatients. 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.
Authors: Michael Sand; Thilo Gambichler; Marina Skrygan; Daniel Sand; Nina Scola; Peter Altmeyer; Falk G Bechara Journal: Cancer Invest Date: 2010-07 Impact factor: 2.176
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Authors: William M Merritt; Yvonne G Lin; Liz Y Han; Aparna A Kamat; Whitney A Spannuth; Rosemarie Schmandt; Diana Urbauer; Len A Pennacchio; Jan-Fang Cheng; Alpa M Nick; Michael T Deavers; Alexandra Mourad-Zeidan; Hua Wang; Peter Mueller; Marc E Lenburg; Joe W Gray; Samuel Mok; Michael J Birrer; Gabriel Lopez-Berestein; Robert L Coleman; Menashe Bar-Eli; Anil K Sood Journal: N Engl J Med Date: 2008-12-18 Impact factor: 91.245