International journal of biological sciences, 2019-01, Vol.15 (10), p.2075-2086
2019
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- Autor(en) / Beteiligte
- Titel
- Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway
- Ist Teil von
- International journal of biological sciences, 2019-01, Vol.15 (10), p.2075-2086
- Ort / Verlag
- Australia: Ivyspring International Publisher Pty Ltd
- Erscheinungsjahr
- 2019
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- This study aimed to investigate the oncogenic activity of microRNA-10b by targeting CUB and sushi multiple domains protein 1 (CSMD1) in human gastric cancer (GC) and the underlying mechanisms. The expression of CSMD1 in human GC tissues was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemical analysis. The expressive abundance of microRNA-10b was detected by stem-loop RT-PCR. Molecular and cellular techniques, including lentiviral vector-mediated knockdown or overexpression, were used to elucidate the effect of microRNA-10b on the expression of CSMD1. CSMD1 was targeted and downregulated by microRNA-10b in human GC tissues and cells, and the down-regulated expression of CSMD1 contributed to poor survival. The knockdown of microRNA-10b expression inhibited cell proliferation in GC cells and tumor growth The inhibition of microRNA-10b expression repressed invasion and migration of HGC27 cells and retarded GC cells metastasis to the liver in Balb/c nude mice. The up-regulated expression of microRNA-10b promoted the proliferation and metastasis of MKN74 cell Intratumoral injection of microRNA-10b mimic also promoted the growth and metastasis of tumor xenografts in Balb/c nude mice. Mechanistically, microRNA-10b promoted the invasion and metastasis of human GC cells through inhibiting the expression of CSMD1, leading to the activation of the nuclear factor-κB (NF-κB) pathway that links inflammation to carcinogenesis, subsequently resulting in the upregulation of c-Myc, cyclin D1 (CCND1), and epithelial-mesenchymal transition (EMT) markers. The findings established that microRNA-10b is an oncomiR that drives metastasis. Moreover, a set of critical tumor suppressor mechanisms was defined that microRNA-10b overcame to drive human GC progression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1449-2288eISSN: 1449-2288DOI: 10.7150/ijbs.23802Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6775299
- Format
- –
- Schlagworte
- Animals, Blotting, Western, c-Myc protein, Cancer, Carcinogenesis, Carcinogens, Cell migration, Cell proliferation, Cyclin D1, Deregulation, Female, Gastric cancer, Humans, Immunoblotting, Kinases, Liver cancer, Lymphatic system, Medical prognosis, Membrane Proteins - genetics, Membrane Proteins - metabolism, Mesenchyme, Metastases, Metastasis, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, MicroRNAs - genetics, MicroRNAs - metabolism, miRNA, Myc protein, NF-kappa B - genetics, NF-kappa B - metabolism, NF-κB protein, Polymerase chain reaction, Proteins, Research Paper, Reverse Transcriptase Polymerase Chain Reaction, Reverse transcription, Ribonucleic acid, RNA, Signal Transduction - genetics, Signal Transduction - physiology, Stomach Neoplasms - genetics, Stomach Neoplasms - metabolism, Stomach Neoplasms - pathology, Tumor suppressor genes, Tumor Suppressor Proteins - genetics, Tumor Suppressor Proteins - metabolism, Tumors, Xenografts, Xenotransplantation