F-box protein FBXO31 is down-regulated in gastric cancer and negatively regulated by miR-17 and miR-20a.
F-box protein FBXO31 is down-regulated in gastric cancer and negatively regulated by miR-17 and miR-20a.
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F-box 蛋白 FBXO31 在胃癌中下调并受到 miR-17 和 miR-20a 的负调控
DOI：
10.18632/oncotarget.2183
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
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作者：
Zhang X;Kong Y;Xu X;Xing H;Zhang Y;Han F;Li W;Yang Q;Zeng J;Jia J;Liu Z
FBXO 31是SCF泛素连接酶的一个亚基，在神经元发育、DNA损伤反应和肿瘤发生中起重要作用。在这里，我们研究FBXO 31在人原发性胃癌（GC）样本中的表达和预后价值。同时，对FBXO 31的生物学作用和调控机制进行了初步探讨。我们发现FBXO 31 mRNA和蛋白在胃癌组织中的表达与癌旁组织相比显著降低。FBXO 31的表达与肿瘤大小、浸润深度、临床分级及预后有关。FBXO 31过表达可显著降低胃癌细胞集落形成率，使胃癌细胞周期阻滞于G1期，并抑制CyclinD 1蛋白的表达。进一步的证据是从FBXO 31的敲除中获得的。FBXO 31的异位表达显著抑制裸鼠异种移植瘤的生长。miR-20 a和miR-17模拟物分别抑制FBXO 31的表达，而miR-20 a和miR-17的抑制剂则增加FBXO 31的表达。miR-20 a和miR-17直接结合FBXO 31的3 '-UTR。胃癌组织中miR-20 a和miR-17的表达水平显著高于癌旁正常黏膜。此外，在这些GC样品中观察到miR-20 a（miR-17）和FBXO 31之间的高度显著负相关性。因此，靶向miR-20 a（miR-17）-FBXO 31-CyclinD 1通路的有效治疗可能有助于控制GC进展。
FBXO31, a subunit of the SCF ubiquitin ligase, played a crucial role in neuronal development, DNA damage response and tumorigenesis. Here, we investigated the expression and prognosis value of FBXO31 in human primary gastric cancer (GC) samples. Meanwhile, the biological role and the regulation mechanism of FBXO31 were evaluated. We found that FBXO31 mRNA and protein was decreased dramatically in the GC tissue compared with the adjacent non-cancerous tissues. FBXO31 expression was significantly associated with tumor size, tumor infiltration, clinical grade and patients' prognosis. FBXO31 overexpression significantly decreased colony formation and induced a G1-phase arrest and inhibited the expression of CyclinD1 protein in GC cells. Further evidence was obtained from knockdown of FBXO31. Ectopic expression of FBXO31 dramatically inhibited xenograft tumor growth in nude mice. miR-20a and miR-17 mimics inhibited, whereas the inhibitor of miR-20a and miR-17 increased, the expression of FBXO31, respectively. miR-20a and miR-17 directly bind to the 3'-UTR of FBXO31. The level of miR-20a and miR-17 in GC tissue was significantly higher than that in surrounding normal mucosa. Moreover, a highly significant negative correlation between miR-20a (miR-17) and FBXO31 was observed in these GC samples. Therefore, effective therapy targeting the miR-20a (miR-17)-FBXO31-CyclinD1 pathway may help control GC progression.