Zhang Xiuwei, Fu Lin, Xue Dongwei, Zhang Xiupeng, Hao Fengxia, Xie Lingling, He Jiani, Gai Junda, Liu Yuhui, Xu Hongtao, Li Qingchang, Wang Enhua
Department of Pathology, The 1st Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, 110001, People's Republic of China.
Department of Pathology, The 4th Affiliated Hospital of China Medical University, Shenyang, 110032, China.
Virchows Arch. 2017 May;470(5):553-560. doi: 10.1007/s00428-017-2102-6. Epub 2017 Mar 13.
Rsf-1 (HBXAP) was recently reported to play roles in tumorigenesis and tumor progression. There have been many reports referred to Rsf-1 overexpression in various cancers and associated with the malignant behavior of cancer cells. However, the molecular mechanism of Rsf-1 in non-small cell lung cancer aggressiveness remains ambiguous. In the present study, we found that there was a significant association between Rsf-1 overexpression and poor overall survival (p = 0.028) in lung cancer. Furthermore, knockdown of Rsf-1 expression in H1299 and H460 cells with high endogenous Rsf-1 expression inhibited cell migration and invasion and downregulated MMP2 expression and nuclear levels of NF-κB. NF-κB inhibitor could also block the effect of Rsf-1 in regulation of MMP2 expression. Further experiments demonstrated that Rsf-1 depletion restrained NF-κB reporter luciferase activity and downregulated bcl-2 and p-IκB protein level. In conclusion, we demonstrated that Rsf-1 was overexpressed in lung cancer and associated with poor survival. Rsf-1 regulated cell invasion through MMP2 and NF-κB pathway.
Rsf-1（HBXAP）最近被报道在肿瘤发生和肿瘤进展中发挥作用。已有许多报道提及Rsf-1在各种癌症中过表达，并与癌细胞的恶性行为相关。然而，Rsf-1在非小细胞肺癌侵袭性中的分子机制仍不明确。在本研究中，我们发现Rsf-1过表达与肺癌患者较差的总生存期显著相关（p = 0.028）。此外，在具有高内源性Rsf-1表达的H1299和H460细胞中敲低Rsf-1表达可抑制细胞迁移和侵袭，并下调MMP2表达以及NF-κB的核水平。NF-κB抑制剂也可阻断Rsf-1对MMP2表达的调节作用。进一步的实验表明，Rsf-1缺失会抑制NF-κB报告基因荧光素酶活性，并下调bcl-2和p-IκB蛋白水平。总之，我们证明Rsf-1在肺癌中过表达并与不良生存相关。Rsf-1通过MMP2和NF-κB途径调节细胞侵袭。
