A CREB1/miR-433 reciprocal feedback loop modulates proliferation and metastasis in colorectal cancer

Increasing evidence has indicated the prognostic value of miR-433 across a series of malignancy types. However, the underlying mechanisms involved in cancer progression haven't been sufficiently elucidated. In the present work, we found that miR-433 was downregulated in CRC tissues and cell lin...

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Published inAging (Albany, NY.) Vol. 10; no. 12; pp. 3774 - 3793
Main Authors Yan, Li, You, Wei-Qiang, Sheng, Neng-Quan, Gong, Jian-Feng, Hu, Lan-Dian, Tan, Ge-Wen, Chen, Hong-Qi, Wang, Zhi-Gang
Format Journal Article
LanguageEnglish
Published United States Impact Journals 06.12.2018
Subjects
Adenocarcinoma - pathology
Animals
Cell Line, Tumor
Cell Proliferation - physiology
Colorectal Neoplasms - pathology
Computational Biology
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Nude
MicroRNAs - genetics
MicroRNAs - metabolism
Neoplasm Metastasis
Neoplasms, Experimental
Research Paper
JNK1
miR-433
CREB1
colorectal cancer
CCAR1
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Summary:Increasing evidence has indicated the prognostic value of miR-433 across a series of malignancy types. However, the underlying mechanisms involved in cancer progression haven't been sufficiently elucidated. In the present work, we found that miR-433 was downregulated in CRC tissues and cell lines. Ectopic expression of miR-433 obviously suppressed the proliferation, invasion and metastasis activity of CRC cells in vitro and in vivo. CREB1, CCAR1 and JNK1 were highly expressed and negatively correlated with miR-433 expression in CRC. CRC patients with higher expression of CREB1, CCAR1 or JNK1 presented a worse outcome relative to those with lower expression. CREB1 transactivated the expression of miR-433, and CREB1, CCAR1 and JNK1 simultaneously served as its targets, which in turn composed a feedback loop between CREB1 and miR-433. miR-433 blocked cell cycle progression and abolished EMT. Collectively, our study demonstrated the CREB1/miR-433 reciprocal feedback loop restrained the propagation, invasion and metastasis activities of CRC cells through abrogation of cell cycle progression and constraint of EMT.
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ISSN:1945-4589
1945-4589
DOI:10.18632/aging.101671