L Liu1, B Guo1, Y Han1, S Xu1, S Liu2. 1. Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No. 639, Huangpu District, Shanghai, 200011, China. 2. Department of Oral and Maxillofacial-Head & Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road No. 639, Huangpu District, Shanghai, 200011, China. shuli639kt@163.com.
Abstract
PURPOSE: Oral squamous cell carcinoma (OSCC) is the most frequent type of oral cancer and is associated with high mortality. Membrane-associated ring-CH type finger 1 (MARCH1) is an E3 ubiquitin ligase with roles in immune regulation and cancer development. Whether MARCH1 has a specific role in OSCC, and if so through what mechanism, has not been explored. METHODS: Immunohistochemistry was performed to examine MARCH1 expression in OSCC clinical samples and adjacent paracancerous tissues. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot were conducted to determine mRNA expression and protein levels, respectively. Knockdown and overexpression experiments were carried out to evaluate the effects of MARCH1 on proliferation and apoptosis. To test protein-protein interaction, co-immunoprecipitation assay was performed. Finally, tumor cell grafting was utilized to test the function of MARCH in vivo. RESULTS: High MARCH1 expression in OSCC clinical samples correlated with poor patient prognosis. Functionally, MARCH1 knockdown in OSCC cells suppressed proliferation and promoted apoptosis, while MARCH1 overexpression displayed the opposite effects. We identified PH Domain And Leucine Rich Repeat Protein Phosphatase (PHLPP) 2 as an important target of MARCH1. Mechanistically, MARCH1 interacted with PHLPP2 and promoted PHLPP2 ubiquitination. Lastly, MARCH1 knockdown suppressed OSCC tumorigenicity in vivo and increased PHLPP2 protein level. CONCLUSION: Our study uncovered a function of MARCH1 in OSCC and identified PHLPP2 as an important target of MARCH1 to modulate OSCC cell proliferation and apoptosis.
PURPOSE: Oral squamous cell carcinoma (OSCC) is the most frequent type of oral cancer and is associated with high mortality. Membrane-associated ring-CH type finger 1 (MARCH1) is an E3 ubiquitin ligase with roles in immune regulation and cancer development. Whether MARCH1 has a specific role in OSCC, and if so through what mechanism, has not been explored. METHODS: Immunohistochemistry was performed to examine MARCH1 expression in OSCC clinical samples and adjacent paracancerous tissues. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot were conducted to determine mRNA expression and protein levels, respectively. Knockdown and overexpression experiments were carried out to evaluate the effects of MARCH1 on proliferation and apoptosis. To test protein-protein interaction, co-immunoprecipitation assay was performed. Finally, tumor cell grafting was utilized to test the function of MARCH in vivo. RESULTS: High MARCH1 expression in OSCC clinical samples correlated with poor patient prognosis. Functionally, MARCH1 knockdown in OSCC cells suppressed proliferation and promoted apoptosis, while MARCH1 overexpression displayed the opposite effects. We identified PH Domain And Leucine Rich Repeat Protein Phosphatase (PHLPP) 2 as an important target of MARCH1. Mechanistically, MARCH1 interacted with PHLPP2 and promoted PHLPP2 ubiquitination. Lastly, MARCH1 knockdown suppressed OSCC tumorigenicity in vivo and increased PHLPP2 protein level. CONCLUSION: Our study uncovered a function of MARCH1 in OSCC and identified PHLPP2 as an important target of MARCH1 to modulate OSCC cell proliferation and apoptosis.
Authors: Xabier Marichalar-Mendia; Amelia Acha-Sagredo; Maria Jose Rodriguez-Tojo; Natalia Rey-Barja; Miriam Hernando-Rodriguez; Jose Ignacio Aguirregaviria; Jose Manuel Aguirre-Urizar Journal: Anticancer Res Date: 2011-02 Impact factor: 2.480
Authors: George Mihai Nitulescu; Maryna Van De Venter; Georgiana Nitulescu; Anca Ungurianu; Petras Juzenas; Qian Peng; Octavian Tudorel Olaru; Daniela Grădinaru; Aristides Tsatsakis; Dimitris Tsoukalas; Demetrios A Spandidos; Denisa Margina Journal: Int J Oncol Date: 2018-10-16 Impact factor: 5.650