Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A.

Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A.
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抗菌肽LL-37通过上调DNA结合蛋白A促进皮肤鳞状细胞癌的增殖和侵袭

DOI:
10.3892/ol.2016.4865
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发表时间:
2016-09
期刊:
影响因子:
2.9
通讯作者:
Zheng Y
Zheng Y
中科院分区:
医学4区
文献类型:
--
作者:
Wang W;Jia J;Li C;Duan Q;Yang J;Wang X;Li R;Chen C;Yan H;Zheng Y

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抗微生物肽LL-37不仅有助于宿主防御微生物入侵,而且还调节免疫活性、血管生成和细胞增殖。研究表明,LL-37参与多种肿瘤的发展,如肺癌、卵巢癌、乳腺癌和黑色素瘤。然而,LL-37在皮肤鳞状细胞癌(SCC)发展中的作用尚不清楚。本研究采用免疫组织化学方法证实人DNA结合蛋白A(dbpA)在SCC组织中的表达增加。LL-37在刺激SCC A341细胞后,显示促进这些恶性细胞的增殖、迁移和侵袭。LL-37还促进dbpA mRNA和蛋白表达的上调。此外,在使用小干扰RNA沉默这些恶性细胞中的正常dbpA表达后,肿瘤细胞的增殖和侵袭显著降低。当用NF-κB抑制剂PDTC抑制LL-37刺激的细胞过程时,发现dbpA的表达原本上调的表达被下调。总之,本发明证明通过上调dbpA的表达,LL-37可以促进肿瘤细胞的增殖和侵袭,并且该过程依赖于NF-κB信号通路。
The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-κB inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-κB signalling pathway.