Research Article: Alteration of microRNA-4474/4717 expression and CREB-binding protein in human colorectal cancer tissues infected with Fusobacterium nucleatum

Date Published: April 5, 2019

Publisher: Public Library of Science

Author(s): Yu-yang Feng, Dong-zhu Zeng, Ya-nan Tong, Xiao-xue Lu, Guo-dong Dun, Bin Tang, Zhu-jun Zhang, Xin-li Ye, Qian Li, Jian-ping Xie, Xu-hu Mao, Xiang Xue.

http://doi.org/10.1371/journal.pone.0215088

Abstract

Colorectal cancer (CRC) is a common and highly lethal form of cancer. Although the etiologic role of Fusobacterium nucleatum (F. nucleatum) in the development of CRC has been elucidated, the specific tumor molecules involved in the progression of CRC induced by F. nucleatum have not been identified. This study investigated several miRNAs and genes involved in the progression of F. nucleatum-induced CRC by Affymetrix miRNA microarray technology and GeneChip Human Transcriptome Array 2.0. The results suggest that miR-4474 and miR-4717 are up-regulated in CRC tissues in response to F. nucleatum infection, compared with the control group (paracancerous tissues), while other genes associated with signaling pathways in cancer, including CREB-binding protein (CREBBP), STAT1, PRKACB, CAMK2B, JUN, TP53 and EWSR1, were dysregulated. Bioinformatic analysis identified CREBBP as the primary aberrantly expressed gene in F. nucleatum-induced CRC. Consistent with the microarray analysis results, real-time RT-PCR analysis demonstrated that the expression of miR-4474/4717 was upregulated while that of CREBBP mRNA was downregulated in CRC patients infected with F. nucleatum. Additionally, CREBBP was identified as a novel target of miR-4474/4717. The results of this study suggest that miR-4474 and miR-4717 are involved in the progression of F. nucleatum-induced CRC by posttranscriptionally regulating the target gene CREBBP.

Partial Text

Colorectal cancer (CRC) is a common and one of the most lethal cancers ever identified [1], with more than one million new CRC cases are reported annually that result in approximately seven hundred thousand deaths [1]. Fusobacterium nucleatum (F. nucleatum) is a gram-negative anaerobic bacterium associated with periodontitis, appendicitis, Lemierre’s disease, inflammatory bowel disease (IBD) and CRC [2,3,4]. Located at the intestinal interface, F. nucleatum is widely recognized as a risk factor for colorectal carcinogenesis. Previous studies focused on the expression of oncogenes and associated genes in CRC tissues [5,6], while the molecular mechanism of CRC resulting from F. nucleatum infection has not been fully elucidated. Therefore, it is of great importance to screen and identify the specific tumor molecules involved in the progression of CRC induced by F. nucleatum to facilitate further studies on the prevention and therapy of CRC.

Based on the results of this study, miR-4474/4717 and CREBBP are proposed to play important roles in F. nucleatum-induced CRC. First, miR-4474 and miR-4717 were identified in a screen as being associated with F. nucleatum-induced CRC. Subsequently, bioinformatics analysis identified CREBBP as the primary aberrantly expressed gene in F. nucleatum-induced CRC tissue. In addition, the expression of miR-4474/4717 and CREBBP mRNA was demonstrated by real-time RT-PCR analysis, and CREBBP was identified as a novel target of miR-4474/4717. Thus, the results of this study provides new insights into the mechanism of F. nucleatum-induced CRC.

 

Source:

http://doi.org/10.1371/journal.pone.0215088

 

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