4.5 Article

MIR31HG Expression Predicts Poor Prognosis and Promotes Colorectal Cancer Progression

期刊

CANCER MANAGEMENT AND RESEARCH
卷 14, 期 -, 页码 1973-1986

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DOVE MEDICAL PRESS LTD
DOI: 10.2147/CMAR.S351928

关键词

colorectal cancer; lncRNA; MIR31HG; prognosis

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资金

  1. National Natural Science Foundation of China [81402510]

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MIR31HG is upregulated in colorectal cancer patients and its high expression is associated with poor prognosis. GSEA analysis suggests that MIR31HG may be involved in tumorigenesis through modulation of focal adhesion, extracellular matrix organization, integrin cell surface interactions, and focal adhesion-PI3K-Akt-mTOR signaling pathway. Functional experiments demonstrate that silencing of MIR31HG can significantly inhibit migration, invasion, growth, and colony formation in colorectal cancer cells, and alter the expression of key genes related to tumorigenesis.
Purpose: Long noncoding RNAs (lncRNAs) are correlated with cancer pathogenesis and prognosis. Many studies have shown that aberrant expression of MIR31HG is implicated in the cancer progression and patient prognosis. However, the biological function and predictive value of MIR31HG in colorectal cancer is unclear. Methods: The correlation between MIR31HG expression and clinicopathological characteristics of colorectal cancer patients was analyzed by collating the information from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analysis, univariable and multivariable Cox regression analysis were performed to evaluate the prognostic value of MIR31HG. Gene set enrichment analysis (GSEA) was conducted to identify the potential carcinogenic mechanisms implicated in MIR31HG. Moreover, MIR31HG was knocked down using siRNA in colorectal cancer cells, and cell migration, invasion, growth and colony formation assays were performed. The expression of MIR31HG influenced gene markers was quantified by qRT-PCR in MIR31HG-silenced colorectal cancer cells. Results: In TCGA database, we found that MIR31HG was elevated in colorectal cancer patients. The patients with high MIR31HG expression had poor overall survival and disease-specific survival. Univariable and multivariable analyses showed that MIR31HG expression was an independent prognostic predictor in colorectal cancer patients. GSEA revealed that MIR31HG mainly modulated focal adhesion, extracellular matrix organization, integrin cell surface interactions and focal adhesion-PI3K-Akt-mTOR-signaling pathway. Besides, MIR31HG knockdown significantly impaired colorectal cancer cell migration, invasion, growth and colony formation. Further qRT-PCR data confirmed that alteration of MIR31HG expression notably affected the tumorigenesis-related key gene expression in the cells. Conclusion: Our findings provide evidence that MIR31HG is a key factor in maintaining the malignant phenotype of colorectal cancer and act as an independent predictor for patients with colorectal cancer.

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