Phytochemical Regulation of RNA in Treating Inflammatory Bowel Disease and Colon Cancer: Inspirations from Cell and Animal Studies

Guolin Zhang; Chi Zhang; Jia’ao Sun; Yongjian Xiong; Liang Wang; Dapeng Chen

doi:10.1124/jpet.120.000354

Abstract

Recent studies suggest an important role for RNA, especially noncoding RNA, in inflammatory bowel disease (IBD) and colon cancer. Drug development based on regulating RNA rather than protein is a promising new area. Phytochemicals are naturally occurring plant-derived compounds with chemical diversity, biologic activity, easy availability, and low toxicity. Many phytochemicals have been shown to exert protective effects on IBD and colon cancer through modulation of RNAs. The aim of this study was to summarize the advancements of phytochemicals in regulating RNA for the treatment of IBD and colon cancer. This review involves many phytochemicals, including polyphenols, flavones, and alkaloids, which can influence various types of RNAs, including microRNA, long noncoding RNA, as well as messenger RNA, by influencing a variety of upstream molecules or regulating epigenetic processes. The limitation for many current studies is that the specific mechanisms of phytochemicals regulating RNA have not been fully uncovered. Accompanied by more identified functions of RNAs, especially noncoding RNA functions, the screening of RNA-regulating phytochemicals has presented challenges as well as opportunities for the prevention and treatment of IBD and colon cancer.

Significance Statement Noncoding RNAs, which constitute the majority of the human transcriptional genome, play a key role in the disease state and are considered as important therapeutic targets in inflammatory bowel disease (IBD) and colon cancer. Recent studies have shown that phytochemicals regulate the expression of many noncoding RNAs involved in IBD and colon cancer. Therefore, identifying the specific molecular mechanism of phytochemicals regulating noncoding RNA in disease models may result in novel and effective therapeutic opportunities.

Footnotes

Received September 27, 2020.
Accepted December 30, 2020.

↵1 G.Z., C.Z., and J.S. contributed equally to this work.
This work was supported by the National Natural Science Foundation of China [Grant 81600440], the Dalian High Level Talent Support Program [Grant 2017RQ017], and the Basic Research Projects of Liaoning Province Universities [Grant LQ2017042].
The authors declare no conflict of interest.
https://doi.org/10.1124/jpet.120.000354.
↵This article has supplemental material available at jpet.aspetjournals.org.