Dataset Information

Long noncoding RNA lncGALM increases risk of liver metastasis in gallbladder cancer through facilitating N-cadherin and IL-1?-dependent liver arrest and tumor extravasation.

ABSTRACT: Background: Long noncoding RNAs (lncRNA) represent significant factors of the mammalian transcriptome that mediates varied biological and pathological processes. The liver is the most common site for gallbladder cancer (GBC) distant metastasis and contributes to the majority of GBC-related death. How lncRNA affects GBC metastasis is not completely understood.

Results: A novel lncRNA termed lncGALM (lncRNA in GBC associated with liver metastasis) was discovered to be highly expressed in cancer patients and xenografted tumors with liver metastasis. Elevated lncGALM in GBC patients also correlated to decreased survival. Invasion and migration of GBC cells were enhanced through lncGALM, both in vitro and in vivo. lncGALM functioned as sponges by competitively binding to and inactivating miR-200 family members, which increase epithelial-mesenchymal transition-associated transcription factor ZEB1 and ZEB2, leading to a fibroblastic phenotype and increased expression of N-cadherin. In addition, lncGALM bound to IL-1? mRNA and stabilized the IL-1? gene that mediates liver sinusoidal endothelial cell (LSECs) apoptosis. lncGALM-expressing LiM2-NOZ cells acquired a strong ability to migrate and adhere to LSECs, promoting LSECs apoptosis and therefore facilitating tumor cell extravasation and dissemination.

Conclusions: lncGALM promotes GBC liver metastasis by facilitating GBC cell migration, invasion, liver arrest, and extravasation via the invasion-metastasis cascade. Targeting lncGALM may be protective against the development of liver metastasis in GBC patients.

SUBMITTER: Li H

PROVIDER: S-EPMC7653798 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Long noncoding RNA lncGALM increases risk of liver metastasis in gallbladder cancer through facilitating N-cadherin and IL-1β-dependent liver arrest and tumor extravasation.

Li Huaifeng H Hu Yunping Y Jin Yunpeng Y Zhu Yidi Y Hao Yajuan Y Liu Fatao F Yang Yang Y Li Guoqiang G Song Xiaoling X Ye Yuanyuan Y Xiang Shanshan S Gao Yuan Y Zhu Jinhui J Zhang Yijian Y Jiang Lin L Huang Wen W Zhu Jian J Wu Xiangsong X Liu Yingbin Y

Clinical and translational medicine 20201101 7

<h4>Background</h4>Long noncoding RNAs (lncRNA) represent significant factors of the mammalian transcriptome that mediates varied biological and pathological processes. The liver is the most common site for gallbladder cancer (GBC) distant metastasis and contributes to the majority of GBC-related death. How lncRNA affects GBC metastasis is not completely understood.<h4>Results</h4>A novel lncRNA termed lncGALM (lncRNA in GBC associated with liver metastasis) was discovered to be highly expressed ...[more]

PMID: 33252861

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Project description:Interleukin-1β (IL-1β) is one of the most potent pro-inflammatory cytokines implicated in a wide range of autoinflammatory, autoimmune, infectious, and degenerative diseases. Therefore, many researchers have focused on developing therapeutic molecules that inhibit IL-1β-IL-1 receptor 1 (IL-1R1) interaction for the treatment of IL-1-related diseases. Among IL-1-related diseases, osteoarthritis (OA), is characterized by progressive cartilage destruction, chondrocyte inflammation, and extracellular matrix (ECM) degradation. Tannic acid (TA) has been proposed to have multiple beneficial effects, including anti-inflammatory, anti-oxidant, and anti-tumor activities. However, it is unclear whether TA plays a role in anti-IL-1β activity by blocking IL-1β-IL-1R1 interaction in OA. In this study, we report the anti-IL-1β activity of TA in the progression of OA in both in vitro human OA chondrocytes and in vivo rat OA models. Herein, using-ELISA-based screening, natural compound candidates capable of inhibiting the IL-1β-IL-1R1 interaction were identified. Among selected candidates, TA showed hindering IL-1β-IL-1R1 interaction by direct binding to IL-1β using surface plasmon resonance (SPR) assay. In addition, TA inhibited IL-1β bioactivity in HEK-Blue IL-1-dependent reporter cell line. TA also inhibited IL-1β-induced expression of inducible nitric oxide synthase (NOS2), cyclooxygenase-2 (COX-2), IL-6, tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and prostaglandin E2 (PGE2) in human OA chondrocytes. Moreover, TA downregulated IL-1β-stimulated matrix metalloproteinase (MMP)3, MMP13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)4, and ADAMTS5, while upregulating collagen type II (COL2A1) and aggrecan (ACAN). Mechanistically, we confirmed that TA suppressed IL-1β-induced MAPK and NF-κB activation. The protective effects of TA were also observed in a monosodium iodoacetamide (MIA)-induced rat OA model by reducing pain and cartilage degradation and inhibiting IL-1β-mediated inflammation. Collectively, our results provide evidence that TA plays a potential role in OA and IL-1β-related diseases by hindering IL-1β-IL-1R1 interaction and suppressing IL-1β bioactivity.

Dataset Information

Long noncoding RNA lncGALM increases risk of liver metastasis in gallbladder cancer through facilitating N-cadherin and IL-1?-dependent liver arrest and tumor extravasation.

Publications

Long noncoding RNA lncGALM increases risk of liver metastasis in gallbladder cancer through facilitating N-cadherin and IL-1β-dependent liver arrest and tumor extravasation.

Similar Datasets

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