J Cancer 2017; 8(3):354-362. doi:10.7150/jca.16720
RSF1 regulates the proliferation and paclitaxel resistance via modulating NF-κB signaling pathway in nasopharyngeal carcinoma
1. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China.
2. Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, China.
Purpose: Aberrant expression and dysfunction of RSF1 has been reported in diverse human malignancies. However, its exact role in nasopharyngeal carcinoma (NPC) remains unclear.
Methods: The expression of RSF1 mRNA and protein were assayed by qRT-PCR and western blotting, and their correlations with clinicopathological parameters of patients with NPC were further analysed. Lentivirus mediated RSF1 shRNA and RSF1 cDNA were used to knockdown and upregulate the expression of RSF1. CCK8 assays and flow cytometry were applied to monitor the changes of proliferation and paclitaxel sensitivity caused by RSF1 modulation, inhibition of NF-κB pathway by inhibitor Bay 11-7082 and Survivin knockdown. Western blotting was used to detect protein alterations in NF-κB signaling pathway.
Results: Our present study demonstrated that both mRNA and protein expressions of RSF1 were increased and correlated with advanced NPC clinical stage. Functional analyses revealed that RSF1 inhibition or overexpression induced changes in cell cycle, apoptosis, and then led to altered proliferation and paclitaxel sensitivity in diverse NPC cells in vitro. Further mechanism investigation hinted that RSF1 overexpression in NPC CNE-2 cells activated NF-κB pathway and promoted the expression NF-κB dependent genes involved in cell cycle and apoptosis including Survivin. Importantly, inhibition of NF-κB pathway by Bay 11-7082 and knockdown its downstream Survivin reversed the paclitaxel resistance caused by RSF1 overexpression.
Conclusions: Taken together, our data indicate that RSF1 regulates the proliferation and paclitaxel resistance via activating NF-κB signaling pathway and NF-κB-dependent Survivin upregulation, suggesting that RSF1 may be used as a potential therapeutic target in NPC.
Keywords: Nasopharyngeal carcinoma, RSF1, Proliferation, NF-κB, Survivin, Paclitaxel resistance.
Liu Y, Li G, Liu C, Tang Y, Zhang S. RSF1 regulates the proliferation and paclitaxel resistance via modulating NF-κB signaling pathway in nasopharyngeal carcinoma. J Cancer 2017; 8(3):354-362. doi:10.7150/jca.16720. Available from http://www.jcancer.org/v08p0354.htm