miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

Li, Fēi; Li, Xin-ji; Qiao, Li; Shi, Fei; Li, Wen; Li, You; Dang, Yu-Ping; Gu, Weijun; Wang, Xiaogang; Liu, Wei

doi:10.1038/emm.2014.63

Cited by 57 publications

(37 citation statements)

References 26 publications

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“…Repressed ALK4 and MMP11 expression affect endothelial cell activity and prevent them from proliferation, spreading, and tube formation [ 48 ]. These results are consistent with a study that shows ectopic expression of miR-98 inhibits B16-F1 cell migration as well as in vivo metastasis and tumor angiogenesis by reducing interleukin-6 (IL-6) level [ 49 ].…”

Section: Mir-98supporting

confidence: 79%

“…These all lead to an enhanced amount of vascularization occurring. Another increased factor is the amount of CD31, which is another important indicator of tumor angiogenesis [ 49 ]. It has been hypothesized that the CSCs express many pro-angiogenic factors such as VEGF, which lead to the increased amount of angiogenesis in tumor cells.…”

Section: Long Noncoding Rna Malat1mentioning

confidence: 99%

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Noncoding RNAs in Tumor Angiogenesis

Khorshidi

Dhaliwal

Yang

2016

Advances in Experimental Medicine and Biology

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Solid tumors require angiogenesis to grow beyond 2 mm in size. In most cases, tumor cells undergo angiogenic switch and secrete substances that are required for generation of new capillary sprouting from existing blood vessels. Tumor angiogenesis is driven by a complex interplay between pro-angiogenic (VEGF/VEGFR, PDGF/PDGFR) and anti-angiogenic factors (TSP-1/TSP-2) within the tumor microenvironment. In addition, control of tissue remodeling and degradation by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) contribute to tumor angiogenesis. Furthermore, tumor suppressors or oncogenes that control cellular motility and maintain or promote hypoxia (HIFs and MYC) are also actively playing roles in tumor angiogenesis. Noncoding RNAs (ncRNAs), including microRNAs, are a novel class of regulatory molecules that control the gene expression in a posttranscriptional manner. MicroRNAs regulate important physiological processes, such as proliferation, apoptosis, and differentiation, as well as pathological conditions including oncogenesis. Accumulating evidence suggests that microRNAs directly modulate the process of angiogenesis by targeting important angiogenic factors and signaling molecules. Understanding the molecular mechanism behind the regulation of angiogenesis by microRNAs is important due to their therapeutic potential which may lead to improving outcome for cancer patients. Besides, ncRNAs with a regulatory role in angiogenesis, such as long noncoding RNAs (lncRNAs), have been identifi ed in the genome. However, the mechanisms of the vast majority of lncRNAs are currently unknown. For the few lncRNAs characterized at the functional level, accumulating evidence shows that they play important roles in malignant diseases. The function and mechanism in angiogenesis will be described in this chapter.

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Section: Mir-98supporting

confidence: 79%

Section: Long Noncoding Rna Malat1mentioning

confidence: 99%

Noncoding RNAs in Tumor Angiogenesis

Khorshidi

Dhaliwal

Yang

2016

Advances in Experimental Medicine and Biology

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“…In NSCLC, miR-4500 directly targets LIN28B, which has been consistently reported to be associated with let-7 and miR-98. 22,23 TargetScan, miRDB, and TargetMiner revealed that genes other than LIN28B, such as CDC34, PBX3, and FZD3, were predicted as candidate miR-4500 targets. PBX3 is overexpressed in gastric cancer and prostate cancer 24,25 and promotes CRC migration by regulating the MAPK/ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2

Yun

Deng

et al. 2016

Cancer Biology & Therapy

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This study aimed to understand the exact function and potential mechanism of miR-4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was decreased in both CRC cells and tissues, and downregulated miR-4500 indicated advanced tumor stage and poor survival. By bisulfite sequencing analysis, we found that the CpG island in the promoter region of miR-4500 was hypermethylated in CRC cells and tissues compared with normal control cells and non-tumor tissues, respectively. Functionally, gain-and loss-of-function analyses indicated the tumor suppressor role of miR-4500: it suppressed cell proliferation, cell cycle progression, migration, and invasion. Predictive algorithms and experimental analyses identified HMGA2 as a direct target of miR-4500. Reintroducing HMGA2 impaired the inhibitory effects of miR-4500 on cell growth and motility. Clinically, higher HMGA2 protein expression in CRC tissues was associated with advanced tumor stage and poor survival. An inverse correlation was found between miR-4500 levels and HMGA2 protein expression. Taken together, this study provides the first evidence that miR-4500 functions as a novel tumor suppressor in the miR-4500/HMGA2 axis in colorectal carcinogenesis, and restoring miR-4500 expression might represent a promising therapeutic strategy for CRC.Abbreviations: CRC, Colorectal cancer; HMGA2, high mobility group AT-hook 2; 5-aza, 5-aza-2 0 -deoxycytidine

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“…We also found that fascin1 KO BMDCs matured by lipopolysaccharide (LPS) showed reduced secretion of inflammatory cytokines including IL-6 and TNFα. Because IL-6 is shown to promote cell motility of a variety of tumor cell lines (32)(33)(34)(35)(36), we examined whether fascin1-mediated increase in IL-6 is involved in chemotactic migration of DCs. We found that IL-6 signaling is required for effective chemotaxis of mature DCs toward CCL19, thereby linking IL-6 mediated inflammation to chemotaxis of mature DCs.…”

Section: Introductionmentioning

confidence: 99%

Investigation of fascin1, a marker of mature dendritic cells, reveals a New role for IL-6 signaling in chemotaxis

Matsumura

Polz

Singh

et al. 2020

Preprint

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Migration of mature dendritic cells (DCs) to lymph nodes is critical for the initiation of adaptive immunity. While CCR7, a a G-protein-coupled receptor for CCL19/21 chemokines, is known to be essential for chemotaxis of mature DCs, the molecular mechanism linking inflammation to chemotaxis remains unclear.We previously demonstrated that fascin1, an actin-bundling protein, increases chemotaxis of mature DCs. In this paper we showed that fascin1 enhanced Interleukin (IL)-6 secretion and signaling. Furthermore, we demonstrated that IL-6 signaling is required for chemotaxis. Blockage of IL-6 signaling in WT DCs with an anti-IL-6 receptorα (IL-6Rα) antibody inhibited chemotaxis toward CCL19.Likewise, knockout (KO) of IL-6Rα inhibited chemotaxis of BMDCs. The addition of soluble IL-6Rα and IL-6 rescued chemotaxis of IL-6Rα KO BMDCs, underscoring the role of IL-6 signaling in chemotaxis. We found that IL-6 signaling is required for internalization of CCR7, the initial step of CCR7 recycling.CCR7 recycling is known to be essential for CCR7-mediated chemotaxis, explaining why IL-6 signaling is needed for chemotaxis of mature DCs. Our results have identified IL-6 signaling as a new regulatory pathway for CCR7/CCL19-mediated chemotaxis, and suggest that rapid migration of mature DCs to lymph nodes depends on inflammation-associated IL-6 signaling.

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miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6

Cited by 57 publications

References 26 publications

Noncoding RNAs in Tumor Angiogenesis

Noncoding RNAs in Tumor Angiogenesis

MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2

Investigation of fascin1, a marker of mature dendritic cells, reveals a New role for IL-6 signaling in chemotaxis

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