Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway

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 cha...

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Bibliographic Details
Published in:International journal of biological sciences 2019-01, Vol.15 (10), p.2075-2086
Main Authors: Chen, Xiang-Liu, Hong, Lian-Lian, Wang, Kai-Lai, Liu, Xiang, Wang, Jiu-Li, Lei, Lan, Xu, Zhi-Yuan, Cheng, Xiang-Dong, Ling, Zhi-Qiang
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.23802