PPM1D silencing by RNA interference inhibits the proliferation of lung cancer cells

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WORLD JOURNAL OF SURGICAL ONCOLOGY

RESEARCH

Open Access

PPM1D silencing by RNA interference inhibits the proliferation of lung cancer cells Chen Zhang1†, Yuanzhuo Chen1†, Mingsong Wang2, Xianzhen Chen1, Yongxin Li3, E Song4, Xiaoqing Liu1, Sekwon Kim3* and Hu Peng1*

Abstract Background: PPM1D (protein phosphatase, Mg2+/Mn2+ dependent, 1D) has been reported to be involved in multiple human tumors. This study was designed to investigate the functional role of PPM1D in lung cancer cells. Methods: Expression levels of PPM1D were analyzed in A549 and H1299 cells by real-time PCR and Western blotting. Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down PPM1D expression in both cell lines. The effects of PPM1D on lung cancer cell growth were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide), colony formation and flow cytometry assays. Results: Knockdown of PPM1D in lung cancer cells resulted in decreased cell proliferation and impaired colony formation ability. Moreover, flow cytometry analysis showed that knockdown of PPM1D arrested cell cycle at the G0/G1 phase. Furthermore, PPM1D silencing downregulated the expression of cyclin B1 in H1299 cells. Therefore, it is reasonable to speculate that the mechanisms by which PPM1D knockdown alleviates cell growth may be partly via the induction of cell cycle arrest due to the suppression of cyclin B1. Conclusions: These results suggest that PPM1D silencing by RNA interference (RNAi) may be a potential therapeutic approach for the treatment of lung cancer. Keywords: PPM1D, lung cancer, shRNA, cell proliferation, cell cycle

Background Lung cancer is one of the major causes of death in the world [1]. The survival rate of lung cancer remains low despite the development of various treatment modalities [2,3]. Even with advances in chemotherapy and radiotherapy, survival rates for patients with advanced stage disease remain largely unchanged [4]. The best chemotherapeutic agents have limited impact with median patient survival being only 11 to 13 months [5]. This raises the need for improved treatment methods based on molecular targeting of lung cancers [6]. The attention paid to understanding the molecular basis of carcinogenesis as a path for cancer defense is rapidly increasing [7,8]. It * Correspondence: [email protected]; [email protected] † Equal contributors 3 Department of Marine Bio Convergence Science, Specialized Graduate School Science and Technology Convergence, Pukyong National University, Busan 608-737, Republic of Korea 1 Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China Full list of author information is available at the end of the article

has also been identified that targeting specific molecular phenomena of cancer development would be a more specific treatment approach. There are a large number of reports on the successful use of RNA interference (RNAi) to suppress cancer progression for both in vitro and in vivo models [9]. PPM1D (protein phosphatase, Mg2+/Mn2+ depen

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