Qiu Wangwang, Xia Xiaotian, Qiu Zhongling, Guo Minggao, Yang Zhili
Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Department of Nuclear Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Gene. 2017 Oct 30;633:35-41. doi: 10.1016/j.gene.2017.08.024. Epub 2017 Aug 31.
Accumulating evidence has shown that Ras guanylnucleotide releasing peptide 3 (RasGRP3) is up-regulated in several distinct cancer types; however, its role in papillary thyroid cancer (PTC) remains unclear. In this study, we demonstrate that RasGRP3 was overexpressed in PTC tissues and cell lines. Downregulation of RasGRP3 using small interfering (si) RNA significantly inhibited PTC cell proliferation and migration in vitro, and tumor growth in vivo, reflecting an oncogenic role of RasGRP3 in PTC. We subsequently identified that the expression of mouse double minute 2 homolog (MDM2) and phosphorylated Akt (p-Akt) was significantly decreased in RasGRP3-downregulated PTC cells. Overexpression of MDM2 attenuated the function of si-RasGRP3. Taken together, our data show that RasGRP3 exerts its oncogenic effect in PTC through Akt-mediated MDM2 activation. RasGRP3 may serve as a potential new therapeutic target for PTC.
越来越多的证据表明，Ras鸟苷酸释放肽3（RasGRP3）在几种不同的癌症类型中表达上调；然而，其在甲状腺乳头状癌（PTC）中的作用仍不清楚。在本研究中，我们证明RasGRP3在PTC组织和细胞系中过表达。使用小干扰（si）RNA下调RasGRP3可显著抑制PTC细胞的体外增殖和迁移以及体内肿瘤生长，这反映了RasGRP3在PTC中的致癌作用。我们随后发现，在RasGRP3下调的PTC细胞中，小鼠双微体2同源物（MDM2）和磷酸化Akt（p-Akt）的表达显著降低。MDM2的过表达减弱了si-RasGRP3的功能。综上所述，我们的数据表明RasGRP3通过Akt介导的MDM2激活在PTC中发挥致癌作用。RasGRP3可能成为PTC潜在的新治疗靶点。
