Abstract
In recent decades Chinese medicine has been used worldwide as a complementary and alternative medicine to treat cancer. Plenty of studies have shown that microRNAs (miRNAs) play fundamental roles in many pathological processes, including cancer, while the anti-cancer mechanisms of Chinese medicinal herbs targeting miRNAs also have been extensively explored. Our previous studies and those of others on Chinese medicinal herbs and miRNAs in various cancer models have provided a possibility of new cancer therapies, for example, up-regulating the expression of miR-23a may activate the positive regulatory network of p53 and miR-23a involved in the mechanism underlying the anti-tumor effect of berberine in hepatocellular carcinoma (HCC). In this review, we survey the role of Chinese medicinal herbal products in regulating miRNAs in cancer and the use of mediating miRNAs for cancer treatment. In addition, the controversial roles of herb-derived exogenous miRNAs in cancer treatment are also discussed. It is expected that targeting miRNAs would provide a novel therapeutic approach in cancer therapy by improving overall response and survival outcomes in cancer treatment, especially when combined with conventional therapeutics and Chinese medicinal herbal products.
Highlights
With the rapid development of the Human Genome Project, the non-coding sequence that accounts for 99% of the total human genome is attracting more and more attention by researchers
Piwi-interacting RNAs, short interfering RNAs, small nucleolar RNAs and microRNAs [1,2,3]. Among these non-coding RNAs, miRNAs are the most studied ones in the last years. miRNAs are highly conserved non-coding sequences generally composed of 18–24 nucleotides. They have been shown to be involved in RNA silencing and regulation of the expression of target genes by attaching to the 31 untranslated region (31 UTR) of target mRNAs. miRNAs are usually transcribed by RNA polymerase II from their own genes or from introns [4,5]
Based on our original research and a literature study, 14 Chinese medical herbal products including herbal isolates, herbal extracts and herbal compounds can effectively inhibit carcinogenesis, progression and metastasis by targeting different miRNAs (Table 1). Among these miRNAs regulated by Chinese medical herbal products, miR-21 was the most reported miRNA that has been extensively studied in various cancers
Summary
With the rapid development of the Human Genome Project, the non-coding sequence that accounts for 99% of the total human genome is attracting more and more attention by researchers. A Chinese research group found that camptothecin, which is isolated from the stem and bark of Camptotheca acuminata could induce apoptosis in cancer cells by down-regulating miR-125b and activation of the mitochondrial apoptosis pathways by increasing the expression of the Bak1, Mcl1, and p53 genes [29]. Resveratrol induced apoptosis by suppressing miR-21 regulation of BCL-2 protein expression in pancreatic cancer cells [31].
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