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颗粒蛋白前体通过PI3K/pAkt信号通路调节胆管癌细胞的增殖、凋亡和迁移能力。

Progranulin modulates cholangiocarcinoma cell proliferation, apoptosis, and motility via the PI3K/pAkt pathway.

作者信息

Daya Minerva, Loilome Watcharin, Techasen Anchalee, Thanee Malinee, Sa-Ngiamwibool Prakasit, Titapun Attapol, Yongvanit Puangrat, Namwat Nisana

机构信息

Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Sampaloc, Manila, Philippines.

出版信息

Onco Targets Ther. 2018 Jan 18;11:395-408. doi: 10.2147/OTT.S155511. eCollection 2018.

DOI:10.2147/OTT.S155511
PMID:29403285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5783154/
Abstract

Progranulin (PGRN) is a growth factor normally expressed in rapidly cycling epithelial cells for growth, differentiation, and motility. Several studies have shown the association of PGRN overexpression with the progression of numerous malignancies, including cholangiocarcinoma (CCA). However, the underlying mechanisms on how PGRN modulates CCA cell proliferation and motility is not clear. In this study, we investigated the prognostic significance of PGRN expression in human CCA tissue and the mechanisms of PGRN modulation of CCA cell proliferation and motility. We found that CCA tissues with high PGRN expression were correlated with poor prognosis and likelihood of metastasis. PGRN knockdown KKU-100 and KKU-213 cells demonstrated a reduced rate of proliferation and colony formation and decreased levels of phosphatidyl inositol-3-kinase (PI3K) and phosphorylated Akt (pAkt) proteins. Accumulation of cells at the G1 phase was observed and was accompanied by a reduction of cyclin D1 and CDK4 protein levels. Knockdown cells also induced apoptosis by increasing the Bax-to-Bcl-2 ratio. Increased cell apoptosis was confirmed by annexin V-FITC/PI staining. Moreover, suppression of PGRN reduced CCA cell migration and invasion in vitro. Investigating the biomarkers in epithelial-mesenchymal transition (EMT) revealed a decrease in the expression of vimentin, snail, and metalloproteinase-9. In conclusion, our findings imply that PGRN modulates cell proliferation by dysregulating the G1 phase, inhibiting apoptosis, and that it plays a role in the EMT affecting CCA cell motility, possibly via the PI3K/pAkt pathway.

摘要

颗粒蛋白前体（PGRN）是一种生长因子，通常在快速增殖的上皮细胞中表达，参与细胞生长、分化和运动。多项研究表明，PGRN过表达与包括胆管癌（CCA）在内的多种恶性肿瘤的进展相关。然而，PGRN调节CCA细胞增殖和运动的潜在机制尚不清楚。在本研究中，我们调查了PGRN在人CCA组织中的表达的预后意义以及PGRN调节CCA细胞增殖和运动的机制。我们发现，PGRN高表达的CCA组织与预后不良和转移可能性相关。PGRN敲低的KKU-100和KKU-213细胞增殖率和集落形成率降低，磷脂酰肌醇-3-激酶（PI3K）和磷酸化Akt（pAkt）蛋白水平降低。观察到细胞在G1期积累，并伴有细胞周期蛋白D1和细胞周期蛋白依赖性激酶4（CDK4）蛋白水平降低。敲低细胞还通过增加Bax与Bcl-2的比值诱导细胞凋亡。膜联蛋白V-异硫氰酸荧光素/碘化丙啶（annexin V-FITC/PI）染色证实细胞凋亡增加。此外，抑制PGRN可降低CCA细胞在体外的迁移和侵袭能力。对上皮-间质转化（EMT）生物标志物的研究显示波形蛋白、蜗牛蛋白和基质金属蛋白酶-9的表达降低。总之，我们的研究结果表明，PGRN通过失调G1期、抑制细胞凋亡来调节细胞增殖，并且它可能通过PI3K/pAkt途径在影响CCA细胞运动的EMT中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/11a71fe33aa6/ott-11-395Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/0637280b3026/ott-11-395Fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/703745601231/ott-11-395Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/efbd316648e5/ott-11-395Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/b8a607ffa68e/ott-11-395Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/357050afca7b/ott-11-395Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/652d907ebbf2/ott-11-395Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/44ffe02fc2e9/ott-11-395Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/11a71fe33aa6/ott-11-395Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/0637280b3026/ott-11-395Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/a37ff872c0d6/ott-11-395Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/703745601231/ott-11-395Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/efbd316648e5/ott-11-395Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/b8a607ffa68e/ott-11-395Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/357050afca7b/ott-11-395Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/652d907ebbf2/ott-11-395Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/44ffe02fc2e9/ott-11-395Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b268/5783154/11a71fe33aa6/ott-11-395Fig9.jpg

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本文引用的文献

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2
Update on the Diagnosis and Treatment of Cholangiocarcinoma.胆管癌诊断与治疗的最新进展
Curr Gastroenterol Rep. 2017 Jan;19(1):2. doi: 10.1007/s11894-017-0542-4.
3
Mechanisms of Progranulin Action and Regulation in Genitourinary Cancers.颗粒蛋白前体在泌尿生殖系统癌症中的作用及调控机制
颗粒蛋白前体（PGRN）在多形性胶质母细胞瘤发病机制中的作用。
Cells. 2024 Jan 10;13(2):124. doi: 10.3390/cells13020124.
4
Progranulin Oncogenic Network in Solid Tumors.实体瘤中的原颗粒蛋白致癌网络。
Cancers (Basel). 2023 Mar 10;15(6):1706. doi: 10.3390/cancers15061706.
5
PGRN exacerbates the progression of non-small cell lung cancer via PI3K/AKT/Bcl-2 antiapoptotic signaling.颗粒蛋白前体通过PI3K/AKT/Bcl-2抗凋亡信号通路加剧非小细胞肺癌的进展。
Genes Dis. 2021 Jul 1;9(6):1650-1661. doi: 10.1016/j.gendis.2021.05.005. eCollection 2022 Nov.
6
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7
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9
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