Expression analysis of inflammasome sensors and implication of NLRP12 inflammasome in prostate cancer.
Expression analysis of inflammasome sensors and implication of NLRP12 inflammasome in prostate cancer.
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DOI：
10.1038/s41598-017-04286-4
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发表时间：
2017-06-29
影响因子：
4.6
通讯作者：
Dubey S
中科院分区：
文献类型：
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作者：
Karan D;Tawfik O;Dubey S
炎性小体是一种多蛋白复合体，调节炎症相关信号传导。虽然炎症在癌细胞生长中起着关键作用，但关于炎性小体在前列腺癌中的作用的研究仍然没有得到表征。使用基因表达综合数据集（GEO）公开数据集，我们筛选了前列腺肿瘤组织中炎性体传感器NLRP 3、NLRC 4、NLRP 6、NRLP 12和AIM 2的表达谱，并在一组前列腺癌细胞系中验证了它们的mRNA水平。验证了NLRP 3和NLRP 12炎性体的选择性表达，并在人前列腺存档肿瘤组织中评价了临床相关性。我们观察到，除了NLRP 12外，炎性小体传感器的表达在mRNA水平上失调。NLRP 12在恶性前列腺组织中的表达强度明显高于其邻近的良性前列腺组织。相反，NLRP 3在前列腺组织中的免疫染色是异质的。炎性复合体蛋白ASC（包含CARD的前列腺增生相关斑点样蛋白）和半胱天冬酶原-1及其下游靶点IL-1β和IL-18仅限于侵袭性前列腺癌细胞。这些数据表明NLRP 12的表达增加与前列腺癌相关，并支持NLRP 12炎性体复合物调节炎性细胞因子在理解前列腺癌中炎症作用中的作用。
Inflammasomes are multi-proteins complex regulating inflammation-associated signaling. While inflammation plays a critical role in cancer cell growth, studies remain uncharacterized on the role of inflammasomes in prostate cancer. Using Gene Expression Omnibus (GEO) public datasets, we screened the expression profiles of inflammasome sensors NLRP3, NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel of prostate cancer cell lines. The selected expression of NLRP3 and NLRP12 inflammasomes was validated, and the clinical association was evaluated in human prostate archival tumor tissues. We observed that the expression of inflammasome sensors was dysregulated at the mRNA level except for the NLRP12. The intensity of NLRP12 immunostaining was significantly higher in malignant prostate as compared to their adjacent benign tissues. In contrast, the NLRP3 immunostaining in prostate tissues was heterogeneous. The inflammasome complex proteins ASC (apoptosis-associated speck-like protein containing a CARD) and pro-caspase-1, as well as its downstream targets IL-1β and IL-18 were confined to aggressive prostate cancer cells. These data suggest an increased expression of NLRP12 in association with prostate cancer and support the role of NLRP12 inflammasome complex regulating inflammatory cytokines in understanding the role of inflammation in the prostate cancer.