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HGF-mediated S100A11 overexpression enhances proliferation and invasion of gastric cancer.

ABSTRACT: S100 proteins are a group of low molecular weight (10-12 kDa) acidic proteins belonging to the largest family of EFhand calciumbinding proteins. S100A11, also known as S100C or calgizzarin, is an important member of the S100 family. S100A11 overexpression has been reported in a number of cancers including papillary thyroid carcinoma, colon, pancreatic, and breast cancer. One other study demonstrated that increased S100A11 expression is correlated with gastric cancer metastasis and poor overall disease prognosis. This study aimed to identify the function of S100A11 associated with cell proliferation and invasion in gastric cancer. We used cell culture, western blotting, reverse transcription-polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and S100A11 knock-down with short hairpin ribonucleic acid (shRNA). First, we confirmed that the S100A11 expression was upregulated by hepatocyte growth factor (HGF). The role of S100A11 was determined via knock down of S100A11. S100A11-shRNA cells showed decreased levels of metalloproteinase-9 (MMP9) and nuclear factor kappa-B (NF-?B). We also examined and confirmed the role of HGF-mediated S100A11 expression. HGF-mediated cell proliferation and in vitro invasion increased, and HGF-mediated apoptosis decreased in S100A11 knockdown cells. We identified the putative binding site of NF-?B in the MMP9 promoter region and confirmed its function via chromatin immunoprecipitation (CHIP) assay. Our results showed that S100A11 is upregulated by HGF through the NF-?B pathway in gastric cancer and plays a role in cell proliferation and invasion in gastric cancer. It may thus be a possible target for gastric cancer therapy.

SUBMITTER: Koh SA

PROVIDER: S-EPMC6291695 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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HGF-mediated S100A11 overexpression enhances proliferation and invasion of gastric cancer.

Koh Sung Ae SA Lee Kyung Hee KH

American journal of translational research 20181115 11

S100 proteins are a group of low molecular weight (10-12 kDa) acidic proteins belonging to the largest family of EFhand calciumbinding proteins. S100A11, also known as S100C or calgizzarin, is an important member of the S100 family. S100A11 overexpression has been reported in a number of cancers including papillary thyroid carcinoma, colon, pancreatic, and breast cancer. One other study demonstrated that increased S100A11 expression is correlated with gastric cancer metastasis and poor overall d ...[more]

PMID: 30662594

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Project description:Purpose:Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC. Patients and Methods:MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients' tissues and serum were detected by qRT-PCR, and their correlation with patients' pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report. Results:The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ?3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and ?-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level. Conclusion:Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC.

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HGF-mediated S100A11 overexpression enhances proliferation and invasion of gastric cancer.

Publications

HGF-mediated S100A11 overexpression enhances proliferation and invasion of gastric cancer.

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