The RNA binding protein neuro‐oncological ventral antigen 1 (NOVA1) regulates IL-6 mRNA stability to enhance JAK2-STAT3 signaling in CRC

Autor: Li-qiang Hao, Jun-sheng Ni, Qizhi Liu, Yong-Gang Hong, Guo-shu Xu, Guan-yu Yu, Wei Zhang, Ji-dian Zhou, Hong-Li Yan
Rok vydání: 2019
Předmět:
Male
STAT3 Transcription Factor
0301 basic medicine
Lung Neoplasms
RNA Stability
Apoptosis
RNA-binding protein
Matrix metalloproteinase
Metastasis
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Cell Movement
Neuro-Oncological Ventral Antigen
Biomarkers
Tumor
Tumor Cells
Cultured
Animals
Humans
Medicine
Neoplasm Invasiveness
STAT3
Interleukin 6
Cell Proliferation
Messenger RNA
biology
Interleukin-6
business.industry
RNA-Binding Proteins
Janus Kinase 2
Middle Aged
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
digestive system diseases
Gene Expression Regulation
Neoplastic
Survival Rate
030104 developmental biology
Oncology
Cell culture
030220 oncology & carcinogenesis
biology.protein
Cancer research
Female
Surgery
Neoplasm Recurrence
Local
Colorectal Neoplasms
business
Follow-Up Studies
Zdroj: Surgical Oncology. 31:67-74
ISSN: 0960-7404
DOI: 10.1016/j.suronc.2019.09.009
Popis: The molecular mechanisms governing the metastasis of colorectal cancer (CRC) are incompletely understood. In the present study, we found NOVA1 to be expressed at higher levels in CRC cell lines and tissue samples, and this upregulation was positively correlated with TNM stage (p = 0.034), poor differentiation (p = 0.001), and lymph node metastasis (p = 0.008). Both overall survival (OS) and relapse-free survival (RFS) were both significantly decreased in patients with high NOVA1 expression relative to those with low expression. Through a multivariate analysis, we determined that NOVA1 independently predicted poor outcomes in those with CRC. In further functional studies, we found that NOVA1 expression controlled the proliferation and invasive characteristics of CRC cells via a mechanism wherein NOVA1 bound and stabilized the IL6 mRNA, enhancing IL-6/JAK2/STAT3 signaling to in turn upregulate matrix metalloproteinases (MMPs) 2, 7, and 9. NOVA1 therefore plays key functional roles in regulating CRC progression, and our results further indicate that it serve as a valuable prognostic biomarker and potentially a target for therapeutic treatment in individuals with CRC.
Databáze: OpenAIRE
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