Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy.
Using CRISPR/Cas9 to Knock out Amylase in Acinar Cells Decreases Pancreatitis-Induced Autophagy.
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DOI：
10.1155/2018/8719397
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发表时间：
2018
影响因子：
--
通讯作者：
Ogawa Y
中科院分区：
文献类型：
--
作者：
Yasunaga K;Ito T;Miki M;Ueda K;Fujiyama T;Tachibana Y;Fujimori N;Kawabe K;Ogawa Y
胰腺癌是一种起源于腺泡细胞的恶性肿瘤。腺泡细胞被重新编程为导管细胞，导致胰腺癌。胰腺炎是一种腺泡细胞炎症，导致“自噬通量受损”。胰腺炎促进腺泡到导管的转分化。淀粉酶的表达在胰腺癌的进展过程中被消除。淀粉酶被认为是腺泡细胞标记物；然而，它在细胞中的功能尚不清楚。因此，我们研究了淀粉酶是否影响腺泡细胞自噬以及它是否在胰腺炎的发展中发挥作用。在这里，我们使用 CRISPR/Cas9 敲除胰腺癌细胞和腺泡细胞中的 ATG12。自噬抑制导致导管细胞标记物表达增加，同时腺泡细胞标记物表达减少。它还导致细胞活力增加和线粒体形态变化。接下来，我们敲除腺泡细胞中的淀粉酶。淀粉酶缺乏减少了胰腺炎引起的自噬。我们的结果表明淀粉酶控制胰腺炎诱导的自噬。我们发现消除淀粉酶表达可通过减少自噬来促进胰腺癌病因。此外，我们的结果表明淀粉酶在选择性胰腺炎诱导的胰腺酶囊泡自噬中发挥作用。
Pancreatic cancer is a malignant neoplasm that originates from acinar cells. Acinar cells get reprogrammed to become duct cells, resulting in pancreatic cancer. Pancreatitis is an acinar cell inflammation, leading to “impaired autophagy flux”. Pancreatitis promotes acinar-to-ductal transdifferentiation. Expression of amylase gets eliminated during the progression of pancreatic cancer. Amylase is considered as an acinar cell marker; however, its function in cells is not known. Thus, we investigated whether amylase affects the acinar cell autophagy and whether it plays any role in development of pancreatitis. Here, we knocked out ATG12 in a pancreatic cancer cells and acinar cells using CRISPR/Cas9. Autophagy inhibition led to an increase in the expression of duct cell markers and a simultaneous decrease in that of acinar cell markers. It also caused an increase in cell viability and changes in mitochondrial morphology. Next, we knocked out amylase in acinar cells. Amylase deficiency decreased autophagy induced by pancreatitis. Our results suggest that amylase controls pancreatitis-induced autophagy. We found that eliminating amylase expression contributes to pancreatic cancer etiology by decreasing autophagy. Furthermore, our results indicate that amylase plays a role in selective pancreatitis-induced autophagy of pancreatic enzyme vesicles.
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影响因子：
11.4
作者：
BUISSON, G;DUEE, E;PAYAN, F
通讯作者：
PAYAN, F
影响因子：
4.8
作者：
Grasso, Daniel;Ropolo, Alejandro;Vaccaro, Maria I.
通讯作者：
Vaccaro, Maria I.
影响因子：
5.7
作者：
Fujii, Satoshi;Mitsunaga, Shuichi;Ochiai, Atsushi
通讯作者：
Ochiai, Atsushi
DOI：
10.1126/science.1232033
发表时间：
2013-02-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mali P;Yang L;Esvelt KM;Aach J;Guell M;DiCarlo JE;Norville JE;Church GM
通讯作者：
Church GM
影响因子：
29.4
作者：
Gruber R;Panayiotou R;Nye E;Spencer-Dene B;Stamp G;Behrens A
通讯作者：
Behrens A