RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis.
RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis.
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3p24 处的 RBMS3 通过抑制细胞增殖、血管生成和诱导细胞凋亡来抑制鼻咽癌的发展。
DOI：
10.1371/journal.pone.0044636
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Guan XY
中科院分区：
文献类型：
--
作者：
Chen J;Kwong DL;Zhu CL;Chen LL;Dong SS;Zhang LY;Tian J;Qi CB;Cao TT;Wong AM;Kong KL;Li Y;Liu M;Fu L;Guan XY
3号染色体短臂缺失是包括鼻咽癌（NPC）在内的许多实体瘤中最常见的遗传学改变之一，表明在频繁缺失的区域内存在一个或多个肿瘤抑制基因（TSGs）。在我们以前的研究中，已经鉴定了一个假定的TSG RBMS 3（RNA结合基序，单链相互作用蛋白3），位于3 p24-p23。在此，我们报道了在3/3的NPC细胞系和13/15（86.7%）的原发性NPC组织中检测到RBMS 3的下调。使用过表达和抑制系统的功能研究表明，RBMS 3在NPC中具有很强的肿瘤抑制作用。RBMS 3的肿瘤抑制机制与其通过上调p53和p21，下调细胞周期蛋白E和CDK 2，以及随后的Rb-丝氨酸780抑制而在G1/S检查点的细胞周期阻滞中的作用有关。进一步的分析表明，RBMS 3通过激活caspase-9和PARP以细胞依赖性方式具有促凋亡作用。最后，RBMS 3抑制微血管形成，这可能是通过MMP 2和β-catenin的下调及其下游靶点（包括cyclin-D1、c-Myc、MMP 7和MMP 9）的失活介导的。综上所述，我们的研究结果确定了RBMS 3作为NPC中重要的肿瘤抑制基因的功能。
Deletion of the short arm of chromosome 3 is one of the most frequent genetic alterations in many solid tumors including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3 (RNA binding motif, single stranded interacting protein 3), located at 3p24-p23, has been identified in our previous study. Here, we reported that downregulation of RBMS3 was detected in 3/3 NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional studies using both overexpression and suppression systems demonstrated that RBMS3 has a strong tumor suppressive role in NPC. The tumor suppressive mechanism of RBMS3 was associated with its role in cell cycle arrest at the G1/S checkpoint by upregulating p53 and p21, downregulating cyclin E and CDK2, and the subsequent inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro-apoptotic role in a mitochondrial-dependent manner via activation of caspase-9 and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated by down-regulation of MMP2 and β-catenin and inactivation of its downstream targets, including cyclin-D1, c-Myc, MMP7, and MMP9. Taken together, our findings define a function for RBMS3 as an important tumor suppressor gene in NPC.
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影响因子：
50.3
作者：
Ahn, G-One;Brown, J. Martin
通讯作者：
Brown, J. Martin
影响因子：
11.2
作者：
Fu, Li;Qin, Yan-Ru;Guan, Xin-Yuan
通讯作者：
Guan, Xin-Yuan
影响因子：
5.2
作者：
Iwai, Soichi;Yonekawa, Atsuko;Yura, Yoshiaki
通讯作者：
Yura, Yoshiaki
DOI：
10.1073/pnas.93.20.10589
发表时间：
1996-10-01
影响因子：
11.1
作者：
Gnarra, JR;Zhou, SB;Linehan, WM
通讯作者：
Linehan, WM
影响因子：
6.4
作者：
Li, H. M.;Man, C.;Tsao, S. W.
通讯作者：
Tsao, S. W.