Published online Sep 21, 2019. doi: 10.3748/wjg.v25.i35.5300
Peer-review started: May 16, 2019
First decision: June 16, 2019
Revised: July 11, 2019
Accepted: July 19, 2019
Article in press: July 19, 2019
Published online: September 21, 2019
Circular RNAs (circRNAs) are considered to be highly stable due to their closed structure, which are predominately correlated with the development and progression of a wide variety of cancers. A recent study demonstrated the upregulated expression of circPIP5K1A in non-small cell lung cancer. However, few studies have investigated the relationship between circ_0014130 level and colon cancer. Therefore, elucidating the underlying mechanisms of circPIP5K1A’s role may help identify novel diagnostic and therapeutic targets for colon cancer.
It is necessary to explore whether circPIP5K1A regulates miR-1273a to affect cell death, cell invasion, and migration in colon cancer. Recent studies have demonstrated that circPIP5K1A exerts an oncogenic role in non-small cell lung cancer, which made it a good lead for further studies regarding the mechanism of circPIP5K1A regulation during colon cancer development.
In this study, we evaluated the expression level of circPIP5K1A in clinical tumor samples and colon cancer cells, and then investigated the effects of circPIP5K1A on colon cell apoptosis and migration in vitro by gain- and loss-of–function approaches. Moreover, we explored whether circPIP5K1A promotes colon cancer development through sponging miR-1273a. Our study provides significant insights into the mechanism of circPIP5K1A during colon cancer development that may contribute to the future design of more effective therapies.
First, circPIP5K1A level was detected in colon cancer tissue and cell lines by RT-qPCR assay. Then gene transfection or silencing experiments were conducted to construct stably expressed or depleted circPIP5K1A cell lines to complete subsequent functional studies. A series of in vitro experiments, such as cell apoptosis assay and Transwell assays, were performed to explore the effects of circPIP5K1A on cell apoptosis, invasion and migration. The potential miRNAs and mRNAs bound to the promoter regions of circPIP5K1A were predicted, and then the potential miRNAs and mRNAs bound to circPIP5K1A sequence were further predicted using RegRNA2.0. MiR-1273a vector was constructed, and then transfected with or without circPIP5K1A vector into colon cancer cells. Then the expression of AP-1, IRF-4, CDX-2, and Zic-1 was detected by western blotting.
CircPIP5K1A was significantly upregulated in colon cancer tissue relative to their adjacent normal tissues. The results of in vitro experiments showed a positive role of circPIP5K1A in the proliferation, invasion, and migration of colon cancer cells. Bioinformatics prediction program predicted that the association of circPIP5K1A with miR-1273a, as well as AP-1, IRF-4, CDX-2, and Zic-1. Further study revealed that the overexpression of circPIP5K1A significantly upregulated both the mRNA and protein level of AP-1, while attenuating the expression of IRF-4, CDX-2, and Zic-1. Conversely, overexpression of miR-1273a clearly alleviated the circPIP5K1A-mediated suppression of IRF-4, CDX-2 and Zic-1 expression.
In conclusion, circPIP5K1A is selectively increased in colon cancer, and circPIP5K1A plays a positive role in colon cancer cell proliferation, invasion, and migration. In addition, overexpression of circPIP5K1A augmented AP-1 expression but attenuated the expression of IRF-4, CDX-2, and Zic-1, while overexpression of miR-1273a inhibited the oncogenic role of circPIP5K1A in progression of colon cancer development.
Our study illuminates the role and molecular mechanism of circPIP5K1A in the regulation of colon cancer development, and demonstrates the oncogenic role of the circPIP5K1A-miR-1273a axis in regulating colon cancer development. The findings of this study provide novel insights into colon cancer pathogenesis.