<p>LCN2 Mediated by IL-17 Affects the Proliferation, Migration, Invasion and Cell Cycle of Gastric Cancer Cells by Targeting SLPI</p>

Abstract

Introduction Gastric cancer occurred in China and even the whole East Asia with high incidence. The objective of this study was to investigate the role of IL-17 in gastric cancer cells mediated by LCN2 binding to SLPI . Methods The expression of LCN2 and SPLI in gastric cancer cells and transfection effects were confirmed by RT-qPCR analysis. The proliferation, clone formation ability, invasion, migration, apoptosis, and cell cycle of gastric cancer cells were in turn detected by CCK-8 assay, clone formation assay, transwell assay, wound healing assay, and flow cytometry analysis. The combination between LCN2 and SLPI was determined by co-immunoprecipitation assay. The expression of Caspase-3, Bcl-2, cyclinB1, cyclinD1, MMP9, and SLPI in gastric cancer cells was detected by Western blot analysis. Results LCN2 and SPLI exhibited the highest levels in AGS cells, and thus AGS cells were selected for the next experiments. Down-regulation of LCN2 suppressed the proliferation and clone formation ability of AGS cells treated with IL-17 . IL-17 promoted the invasion and migration of AGS cells, which was partially reversed by the down-regulation of LCN2 . Down-regulation of LCN2 mediated by IL-17 promoted apoptosis and suppressed the cell cycle of AGS cells. Discussion Down-regulation of LCN2 mediated by IL-17 suppressed the proliferation and suppressed the migration and invasion and cell cycle of gastric cancer cells by targeting SLPI .

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“…Previous studies have shown that high LCN2 expression levels were correlated with poor prognosis in breast cancer patients [ 17 , 25 , 26 , 27 ]. We further validated these findings by analyzing a meta‐dataset of 8951 breast cancers, in which 87% of tumor samples were classified as LCN2 ‐low ( n = 7830/8951) and 13% as LCN2 ‐high ( n = 1121/8951).…”

“…LCN2 has been implicated in the progression of several types of human tumors. LCN2 expression is higher in solid tumors than in corresponding normal tissues [ 25 , 41 ], and it is mainly described as tumor promoter in many cancers, including pancreas, glioblastoma, thyroid, kidney, esophagus, and breast cancer [ 19 , 28 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

“…Here, we report that LCN2 could regulate cell cycle‐associated proteins such as FOXM1, Chk1, CDK1, Aurora‐B, Wee1, and cyclin‐B1 to promote its oncogenic role in IBC tumors. Others have also found that silencing of LCN2 affected the expression of cell cycle proteins by reducing cyclin‐D1 and inducing p21, resulting in G0‐G1 cell cycle arrest [ 22 , 24 , 25 ].…”

“…LCN2 is known to sequester iron, as it binds siderophore‐complexed ferric iron with high affinity, and has significant roles in immune and inflammatory responses, angiogenesis, cell proliferation, survival, and resistance to anticancer therapies [ 16 , 17 , 18 , 19 , 20 , 21 ]. LCN2 has been implicated in the progression of several types of human tumors, including breast cancer, through several mechanisms, such as stabilization of matrix metallopeptidase 9 (MMP‐9), sequestration of iron, induction of epithelial–mesenchymal transition, apoptosis resistance, lymphangiogenesis, and cell cycle arrest [ 16 , 17 , 18 , 19 , 20 , 22 , 23 , 24 , 25 , 26 ]. Moreover, high LCN2 expression levels have been linked with poorer survival in patients with breast cancer [ 16 , 26 , 27 , 28 ].…”

Network Pharmacology-Based Approach to Investigate the Mechanisms of Piwei-Peiyuan Decoction in the Treatment of Gastric Carcinoma

“…A study 43 showed that the median serum IL-17 level in GC patients was signi cantly higher than that in controls (9.04 VS 8.07 pg/ml, p=0.01), which shows that serum IL-17 level can be used as a new potential indicator for GC diagnosis. Xu J et al 44 found that IL-17-mediated downregulation of LCN2 expression inhibited the proliferation, migration, and invasion of GC cells by regulating SLPI. In addition to IL-17A, a member of the IL-17 family, several experiments have con rmed that IL-17B/IL-17 receptor B (IL-17RB) can inhibit growth and progression of tumor.…”