Journal
CANCER LETTERS
Volume 388, Issue -, Pages 177-186Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.11.039
Keywords
Mus81; Hepatocellular carcinoma; STC2; Proliferation; Apoptosis
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Funding
- Natural Science Foundation of China [81000989]
- Natural Science Foundation of Guangdong Province, China [10451022002004562, 2014A030313654]
- Project of Science & Technology New Star of Pearl River, Guangzhou City, China [2011J2200008]
- Special Support Projection for High-Level Talents of Guangdong Province, China [2014TQ01R482]
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Methyl methansulfonate and UV sensitive gene clone 81 (Mus81) is a critical DNA repair gene that has been implicated in development of several cancers including hepatocellular carcinoma (HCC). However, whether Mus81 can affect proliferation and survival of HCC remains unknown. In the present study, we demonstrated that the knockdown of Mus81 was associated with suppressed proliferation and elevated apoptosis of HCC cells in vitro and in vivo. Multilayered screenings, including DNA microarray, high content screen, and real-time PCR validation, identified STC2 as a proliferation-facilitating gene significantly down-regulated in HCC cells upon Mus81 knockdown. STC2 expression was also closely correlated to Mus81 expression in HCC tissues. More importantly, the restoration of STC2 expression recovered the compromised cell proliferation and survival in Mus81 depleted HCC cells. Furthermore, Mus81 knockdown was associated with the activation of APAF1, APC, and PTEN pathways and concurrent inhibition of MAPK pathway through decreasing STC2 expression. In conclusion, Mus81 knockdown suppresses proliferation and survival of HCC cells likely by downregulating STC2 expression, implicating Mus81 as a therapeutic target for HCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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