DHX9 contributes to the malignant phenotypes of colorectal cancer via activating NF-κB signaling pathway
| Autor: | Wei Dai, Junhong Wu, Lu Xie, Lingxia Chen, Fuhua Xie, Xinqiang Wu, Shenglan Liu, Liangmei He, Zhiping Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Epithelial-Mesenchymal Transition Colorectal cancer Mice Nude Apoptosis RNA polymerase II Biology Metastasis DEAD-box RNA Helicases Mice Cellular and Molecular Neuroscience Downregulation and upregulation Survivin Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans RNA Small Interfering neoplasms Molecular Biology Cell Proliferation Pharmacology Mice Inbred BALB C Cell growth Liver Neoplasms NF-kappa B Cell Biology Prognosis medicine.disease Xenograft Model Antitumor Assays Phenotype digestive system diseases Neoplasm Proteins Gene Expression Regulation Neoplastic Survival Rate Cancer research biology.protein Molecular Medicine Phosphorylation Colorectal Neoplasms Signal Transduction |
| Zdroj: | Cellular and Molecular Life Sciences. 78:8261-8281 |
| ISSN: | 1420-9071 1420-682X |
| Popis: | Colorectal cancer (CRC) is the leading cause of cancer-related mortality worldwide, which makes it urgent to identify novel therapeutic targets for CRC treatment. In this study, DHX9 was filtered out as the prominent proliferation promoters of CRC by siRNA screening. Moreover, DHX9 was overexpressed in CRC cell lines, clinical CRC tissues and colitis-associated colorectal cancer (CAC) mouse model. The upregulation of DHX9 was positively correlated with poor prognosis in patients with CRC. Through gain- and loss-of function experiments, we found that DHX9 promoted CRC cell proliferation, colony formation, apoptosis resistance, migration and invasion in vitro. Furthermore, a xenograft mouse model and a hepatic metastasis mouse model were utilized to confirm that forced overexpression of DHX9 enhanced CRC outgrowth and metastasis in vivo, while DHX9 ablation produced the opposite effect. Mechanistically, from one aspect, DHX9 enhances p65 phosphorylation, promotes p65 nuclear translocation to facilitate NF-κB-mediated transcriptional activity. From another aspect, DHX9 interacts with p65 and RNA polymerase II (RNA Pol II) to enhance the downstream targets of NF-κB (e.g., Survivin, Snail) expression to potentiate the malignant phenotypes of CRC. Together, our results suggest that DHX9 may be a potential therapeutic target for prevention and treatment of CRC patients. |
| Databáze: | OpenAIRE |
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