Shanghai Sixth People's Hospital East, Shanghai University of Medicine &Health Sciences, Shanghai 201306, China.
Joint Research Center for Translational Medicine, East China Normal University and Shanghai Fengxian District Central Hospital, Southern Medical University, Nanfeng Road 6600, Shanghai 201499, China.
Sci Rep. 2017 Mar 2;7:43683. doi: 10.1038/srep43683.
Development of castration resistance is a key contributor to mortality in patients with prostate cancer. High expression of RING finger protein 7 (RNF7) in cancer cells is known to play a key role in tumor progression. However, the role of RNF7 in prostate cancer progression is not well elucidated. In this study, we silenced RNF7 by shRNA interference in two castration resistant prostate cancer (CRPC) cell lines, DU145 and PC3. RNF7 knockdown attenuated proliferation and enhanced sensitivity of prostate cancer cells to cisplatin treatment. Invasive property of DU145 and PC3 cells was also attenuated by RNF7 silencing. The underlying mechanisms appear to be associated with accumulation of tumor suppressive proteins p21, p27 and NOXA, while inactivation of ERK1/2 by RNF7 knockdown. We demonstrated that RNF7 knockdown induced growth suppression of prostate cancer cells and inactivated ERK1/2 pathway, which suggested RNF7 might be a potential novel therapeutic target for CRPC.
去势抵抗的发展是导致前列腺癌患者死亡的一个关键因素。已知癌细胞中 RING 指蛋白 7（RNF7）的高表达在肿瘤进展中起着关键作用。然而，RNF7 在前列腺癌进展中的作用尚未得到充分阐明。在这项研究中，我们通过 shRNA 干扰在两种去势抵抗性前列腺癌（CRPC）细胞系 DU145 和 PC3 中沉默了 RNF7。RNF7 敲低减弱了前列腺癌细胞的增殖并增强了它们对顺铂治疗的敏感性。RNF7 沉默也减弱了 DU145 和 PC3 细胞的侵袭性。潜在的机制似乎与肿瘤抑制蛋白 p21、p27 和 NOXA 的积累有关，而 RNF7 敲低使 ERK1/2 失活。我们证明 RNF7 敲低诱导前列腺癌细胞生长抑制并使 ERK1/2 通路失活，这表明 RNF7 可能是 CRPC 的一个潜在新的治疗靶点。
