The role of IL-11 in immunity and cancer

Xu, Dixon H.; Zhu, Ziwen; Wakefield, Mark R.; Xiao, Hualiang; Bai, Qian; Fang, Yujiang

doi:10.1016/j.canlet.2016.01.004

Cited by 88 publications

(80 citation statements)

References 109 publications

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“…However, the downstream effector may be variant in different tissue contexts [23]. Our study showed that although IL-11 has no impact on phosphorylation of ERK1/2 and STAT5, pSTAT3 and AKT were severely upregulated.…”

Section: Discussionmentioning

confidence: 87%

Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Zhao

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Cytokines are key players in tumorigenesis and are potential targets in cancer treatment. Although IL-6 has attracted considerable attention, interleukin 11 (IL-11), another member of the IL-6 family, has long been overlooked, and little is known regarding its specific function in non-small cell lung cancer (NSCLC). In this study, we explored IL-11’s role in NSCLC and the detailed mechanism behind it. Methods: Cell proliferation in response to IL-11 was determined by colony formation, BrdU incorporation and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Cell motility was measured by Transwell and wound healing assays. NSCLC xenograft models were used to confirm oncogenic function of IL-11 in vivo. Immunohistochemical staining and western blot assay were performed to detect epithelial–mesenchymal transition (EMT) markers and cell signaling pathway alterations. Eighteen NSCLC patients and 5 normal lung samples were collected together with data from an online database to determine the link between IL-11 expression and malignant progression. Results: We observed that IL-11 was upregulated in NSCLC samples compared with normal tissue samples and correlated with poor prognosis. Data from in vitro and in vivo models indicated that IL-11 promotes cell proliferation and tumorigenesis. Cell migration and invasion were also enhanced by IL-11. Epithelial–mesenchymal transition (EMT) was also observed after IL-11 incubation. Furthermore, IL-11 activated AKT and STAT3 in our experimental models. In addition, we observed that hypoxia induced IL-11 expression in NSCLC cells. Deferoxamine (DFX) or dimethyloxalylglycine (DMOG) induced hypoxia-inducible factor 1-alpha (HIF1α) upregulation, which enhanced IL-11 expression in NSCLC cells. Conclusions: Taken together, our results indicate that IL-11 is an oncogene in NSCLC, and elucidating the mechanism behind it may provide insights for NSCLC treatment.

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Section: Discussionmentioning

confidence: 87%

Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Zhao

Liu

et al. 2018

Cell Physiol Biochem

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“…Analysis of the miRcode and miRTarBae websites revealed that HOTAIR could potentially interact with miR‐204 and consequently regulate the expression of HOXC8 and interleukin‐11 (IL‐11) (Figure D). Considering the mechanism by which IL‐11 influences cancer has been thoroughly studied, we aimed to investigate the mechanism by which HOTAIR acting as a ceRNA of miR‐204 regulates the expression of HOXC8 in oesophageal cancer cells. Immunohistochemistry and RT‐qPCR were conducted in order to determine the expression pattern of HOXC8, HOTAIR and miR‐204 in the oesophageal cancer tissues as well as the adjacent normal tissues.…”

Section: Resultsmentioning

confidence: 99%

Down‐regulation of long non‐coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up‐regulation of microRNA‐204

Wang

Tan²,

Zhuang³

et al. 2019

J Cellular Molecular Medi

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Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non‐coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA‐204 (miR‐204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR‐204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR‐204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR‐204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR‐204 with siRNA against HOTAIR, miR‐204 mimic or miR‐204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR‐204 was down‐regulated, while HOTAIR and HOXC8 were up‐regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR‐204 and miR‐204 could further target HOXC8. The oesophageal cancer cells treated with si‐HOTAIR or miR‐204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP‐9, but increased E‐cadherin level. Silenced HOTAIR or elevated miR‐204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR‐204 as a competing endogenous RNA and regulate miR‐204 and HOXC8. Hence, down‐regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.

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“…In addition, proteins in C1Q family can be synthesized extrahepatically by epithelial cells, monocytes/macrophages, mesenchymal cells, dendritic cells, trophoblasts, microglial cells, fibroblasts, and endothelial cells, and play an important part in autoimmunity, trophoblast migration, preeclampsia, and cancer (Agostinis et al., ; Ghebrehiwet, Hosszu, Valentino, & Peerschke, ). Moreover, several studies have demonstrated that IL11 specifically binds to IL11RA1 and their binding transmits IL11 signals, and IL‐11 has been implicated in various inflammation‐associated cancers (Xu et al., ). There were also four upregulated DEGs ( C1r , C1qb , C1qa , and C1qc ) enriched in the pathway of complement and coagulation cascades, and six upregulated DEGs, including Csf2ra , Il11ra1 , Itga5 , Csf1r , Cd4 , and Ighm enriched in the pathway of hematopoietic cell lineage in Group Alt compared with Group Que (Table ).…”

Section: Discussionmentioning

confidence: 99%

The Alternate Consumption of Quercetin and Alliin in the Traditional Asian Diet Reshaped Microbiota and Altered Gene Expression of Colonic Epithelial Cells in Rats

Guo

Xie

et al. 2019

Journal of Food Science

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The diet of traditional Asian is similar to the Mediterranean that was considered as a healthy dietary pattern. The report was scarce on whether different plant‐derived components with similar anti‐oxidative and anti‐inflammatory function such as quercetin and alliin in traditional Asian diet consumed in an alternate style cooperatively affect health including the growth of host and the status of the gut microbiota and colonic epithelial immunity. In the present study, the effects of alternate consumption of quercetin and alliin on host health judging by the profile of gut microbiota and gene expression of colonic epithelial cells were investigated with the Illumina MiSeq sequencing (16S rRNA genes) and Illumina HiSeq (RNA‐seq) technique, respectively. The results showed that the alternate consumption significantly increased the rat body weight and reshaped the gut microbiota composition. At the phylum level, it significantly increased the relative abundance of fecal Firmicutes and Cyanobacteria but decreased that of Bacteroidetes (P < 0.05) and increased the relative abundance of Candidatus Arthromitus, Lactococcus, Geobacillus, and Ruminococcus at the genus level that benefits the host's health. The alternate consumption of quercetin and alliin also altered 13 genes expression involved in the KEGG pathways of complement and coagulation cascades and hematopoietic cell lineage to improve the gut immunity. Therefore, the alternate consumption of quercetin and alliin in traditional Asian diet can contribute beneficial metabolic effects by optimizing gut microbiota and altering the immunologic function of colonic epithelial cells, resulting in its potential to improve the sub‐health status.

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The role of IL-11 in immunity and cancer

Cited by 88 publications

References 109 publications

Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Upregulation of IL-11, an IL-6 Family Cytokine, Promotes Tumor Progression and Correlates with Poor Prognosis in Non-Small Cell Lung Cancer

Down‐regulation of long non‐coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up‐regulation of microRNA‐204

The Alternate Consumption of Quercetin and Alliin in the Traditional Asian Diet Reshaped Microbiota and Altered Gene Expression of Colonic Epithelial Cells in Rats

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