PEST-containing nuclear protein regulates cell proliferation, migration, and invasion in lung adenocarcinoma
PEST-containing nuclear protein regulates cell proliferation, migration, and invasion in lung adenocarcinoma
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含有 PEST 的核蛋白调节肺腺癌细胞增殖、迁移和侵袭
DOI：
10.1038/s41389-019-0132-4
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发表时间：
2019-03-14
期刊：
影响因子：
6.2
通讯作者：
Ji，Xin-Ying
中科院分区：
文献类型：
--
作者：
Wang，Da-Yong;Hong，Ya;Ji，Xin-Ying
肺癌是全球癌症相关死亡的主要原因。在癌细胞的细胞核中发现了含有PEST的核蛋白(PCNP)。PCNP是否在肺腺癌的生长中起作用尚不清楚。本研究结果表明，肺腺癌组织中PCNP水平明显高于相应的癌旁组织。PCNP过表达促进肺腺癌细胞的增殖、迁移和侵袭，而下调PCNP则相反。PCNP过表达通过上调磷酸化(P)信号转导和转录激活因子(STAT)3和p-STAT5的表达水平来减少肺腺癌细胞的凋亡，而PCNP基因敲除则表现出相反的趋势。PCNP过表达通过增加p-磷脂酰肌醇3-激酶(PI3K)、p-Akt和p-哺乳动物雷帕霉素靶标(MTOR)的表达水平来增强肺腺癌细胞的自噬作用，而在sh-PCNP组中则呈相反趋势。另外，PCNP过表达对移植肺腺癌有促肿瘤作用，而PCNP基因敲除则通过调节血管生成抑制了肺腺癌的生长。本研究阐明PCNP可能通过STAT3/5和PI3K/Akt/mTOR信号通路调控人肺腺癌细胞的生长。PCNP可作为肺腺癌诊断和预后判断的一种有希望的生物标志物。此外，PCNP可以成为一种新的治疗靶点，并可以设计和开发有效的PCNP抑制剂来治疗肺腺癌。
Lung cancer is the leading cause of cancer-related mortality worldwide. PEST-containing nuclear protein (PCNP) has been found in the nucleus of cancer cells. Whether PCNP plays a role in the growth of lung adenocarcinoma is still unknown. In the present study, the results indicated that the level of PCNP in lung adenocarcinoma tissue was significantly higher than that in corresponding adjacent non-tumor tissue. Over-expression of PCNP promoted the proliferation, migration, and invasion of lung adenocarcinoma cells, while down-regulation of PCNP exhibited opposite effects. PCNP over-expression decreased apoptosis through up-regulating the expression levels of phospho (p)-signal transducers and activators of transcription (STAT) 3 and p-STAT5 in lung adenocarcinoma cells, whereas PCNP knockdown showed opposite trends. PCNP overexpression enhanced autophagy by increasing the expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) in lung adenocarcinoma cells, however an opposite trend was observed in the sh-PCNP group. In addition, overexpression of PCNP showed the tumor-promoting effect on xenografted lung adenocarcinoma, while PCNP knockdown reduced the growth of lung adenocarcinoma via regulating angiogenesis. Our study elucidates that PCNP can regulate the procession of human lung adenocarcinoma cells via STAT3/5 and PI3K/Akt/mTOR signaling pathways. PCNP may be considered as a promising biomarker for the diagnosis and prognosis in patients with lung adenocarcinoma. Furthermore, PCNP can be a novel therapeutic target and potent PCNP inhibitors can be designed and developed in the treatment of lung adenocarcinoma.