Kai Cai1, Yang Yang1, Zi-Jian Guo1, Rui-Lin Cai2, Hiroki Hashida3, Hong-Xia Li1. 1. Department of Oncology, the First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, China. 2. Department of Information Management and Information Systems, Xi'an Jiaotong-Liverpool University, Suzhou, China. 3. Department of Surgery, Kobe City Medical Center General Hospital, Kobe, Japan.
Abstract
Background: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. Methods: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. Results: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/β-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/β-catenin pathway. Conclusions: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/β-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic. 2022 Annals of Translational Medicine. All rights reserved.
Background: Amentoflavone is a type of bioflavonoid that exists in many Chinese medicines and has anti-inflammatory, antioxidant, antiviral, and anticancer effects. However, the effect of amentoflavone on epithelial to mesenchymal transition (EMT) in human colorectal cancer (CRC) has not been studied. In this study, we aim to explore the effect of amentoflavone on EMT in CRC. Methods: The effects of long noncoding RNA (lncRNA) miR-16-5p on proliferation, migration, and invasion were determined by in vitro and in vivo experiments. A luciferase reporter assay was carried out to reveal the interaction between miR-16-5p and targeted genes. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate the expression of miR-16-5p. A western blot assay was used to detect the expression of targeted genes in CRC cells. Results: The results showed that amentoflavone significantly inhibited CRC migration, invasion, and EMT by increasing miR-16-5p expression. Mechanistically, amentoflavone induced inactivation of the Wnt/β-catenin pathway via miR-16-5p, directly targeting 3'-UTR of HMGA2 to suppress HMGA2 expression in CRC. Clinically, combined miR-16-5p and HMGA2 levels may serve as a predictor for poor prognosis in patients with CRC. Furthermore, an in vivo PDX model suggested that amentoflavone exhibited antitumor effects in vivo via the miR-16-5p/HMGA2/β-catenin pathway. Conclusions: This is the first study to show that amentoflavone inhibits CRC EMT via the miR-16/HMGA2/β-catenin pathway. Amentoflavone may be beneficial in treating CRC patients in the clinic. 2022 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
Amentoflavone; HMGA2; colorectal cancer (CRC); epithelial to mesenchymal transition (EMT); miR-16
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