Abstract
BackgroundHoneysuckle is a timeāhonored herb with anticancer activity in traditional Chinese medicine. Recently, accumulating reports are suggesting that the microRNAs in this medicinal plant not only play a physiological role in their original system, but also can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-Ī²1 mRNA.MethodsLuciferase assay was conducted to test the ability of miR2911 to target TGF-Ī²1 mRNA. ELISA was performed to determine the expression level of TGF-Ī²1 of mouse colorectal adenocarcinoma CT26 cells when treated with miR2911 and tumor tissue in Sidt1+/+ and Sidt1ā/ā mice. qRT-PCR was performed to examine the level of expression of miR2911. Tumor-bearing wild and nude mice were employed to evaluate the anti-tumor effect of honeysuckle and miR2911 in vivo. Tumor tissue necrosis was observed by H&E staining. Besides, the infiltration of T lymphocytes across solid tumors was tested by immunostaining staining.ResultsOur results showed that honeysuckle slowed the development of colon cancer down. Further research showed that miR2911 could bind strongly to TGF-Ī²1 mRNA and down-regulate the expression of TGF-Ī²1 and had a high stability under boiling and acid condition. Moreover, SIDT1 mediated dietary miR2911 inter-species absorption. And we found that miR2911 had a similar anticancer effect as honeysuckle. Mechanistically, miR2911 reversed the tumor-promoting effect of TGF-Ī²1 by an increase of T lymphocytes infiltration, resulting in slowing the colon cancer process in immunocompetent mice. Consistent with this inference, the anti-tumor effect of miR2911 was revealed to be abolished in T cell immune deficiency mice.ConclusionTaken together, honeysuckle-derived miR2911 showed an anti-tumor effect in colon cancer through targeting TGF-Ī²1 mRNA. The down-regulation of TGF-Ī²1 promoted T lymphocytes infiltration, and accordingly impeded the colon tumor development.
Highlights
Honeysuckle is a timeāhonored herb with anticancer activity in traditional Chinese medicine
Honeysuckle inhibited the development of Colorectal adenocarcinoma cells (CT26) tumors in vivo As shown in Fig. 1a, we established a CT26 tumor-bearing C57BL/6 mice model to verify the inhibition effect of honeysuckle on colon cancer development in vivo
In the present study, we found that honeysuckle-derived miR2911 could target transforming growth factor-Ī²1 (TGF-Ī²1) and inhibit colon tumor development in immunocompetent mice
Summary
Honeysuckle is a timeāhonored herb with anticancer activity in traditional Chinese medicine. Accumulating reports are suggesting that the microRNAs in this medicinal plant play a physiological role in their original system, and can be transmitted to another species as potential therapeutic components. In the numerous bioactive investigations, the anti-tumor effects of these microRNAs in the magical herb are rarely studied, especially the special miR2911, a honeysuckle-encoded atypical microRNA, with high stability during the boiling process and unique biological activity to target TGF-Ī²1 mRNA. Activation of TGF-Ī²1 signaling pathways inhibited T cell activation and infiltration in tumors [21,22,23]. This means that TGFĪ²1 is a potential therapeutic target for fibrosis, and a target of miR2911 for anticancer therapy
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