PICT1 通过 RPL11 调控 TP53 并参与胃癌的进展。
PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression.
机构信息
1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan [2] Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
出版信息
Br J Cancer. 2013 Oct 15;109(8):2199-206. doi: 10.1038/bjc.2013.561. Epub 2013 Sep 17.
BACKGROUND
The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.
METHODS
To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.
RESULTS
Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).
CONCLUSION
The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
背景
TP53 通路在人类癌症中经常失活。PICT1（也称为 GLTSCR2）通过与核仁中的核糖体蛋白 RPL11 相互作用，成为 MDM2-TP53 通路的新型调节因子。然而，PICT1 在胃癌中的临床意义尚不清楚。
方法
为了评估 PICT1 的功能，我们使用 shRNA 抑制表达野生型 TP53 的胃癌细胞中的 PICT1 表达。在 110 例原发性胃癌中定量检测 PICT1 表达和 TP53 突变状态，以探讨 PICT1 表达水平对胃癌的影响。
结果
通过 TP53 介导的细胞周期阻滞，PICT1 缺失显著损害细胞增殖和集落形成。诱导 PICT1 缺陷后，RPL11 从核仁中易位。在测试的 110 个胃癌样本中，分别有 70（63.6%）和 40（36.4%）肿瘤表达野生型和突变型 TP53。在野生型 TP53 肿瘤的胃癌患者中，与高表达水平患者相比，低表达水平的 PICT1 患者预后较好（P=0.046）。
结论
研究结果表明，PICT1 通过调节 MDM2-TP53 通路，通过 RPL11 在胃癌进展中起关键作用。临床上，PICT1 表达是野生型 TP53 肿瘤胃癌患者的一种新的预后参数。
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