Amentoflavone inhibits colorectal cancer epithelial-mesenchymal transition via the miR-16-5p/HMGA2/β-catenin pathway

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.

Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors

“…Furthermore, in our study, we found that miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, responsible for the epithelial-mesenchymal transition (EMT) of the cell [66][67][68][69][70], were significantly directly correlated with blood serum CA125 concentration and significantly inversely correlated with PGR expression levels in tumor tissue. These elevated levels of miRNAs in tumor tissues and peripheral blood of patients with HGSOC serous ovarian cancer are consistent with literature data showing similar changes in biological samples from patients with serous ovarian tumors [16,[71][72][73][74].…”

Advances in the Anti-Tumor Activity of Biflavonoids in Selaginella

“…Interestingly, Kim et al [77] discovered that the amentoflavone in Selaginella tamariscina is a promising EMT inhibitor of tumor invasion and migration by inhibiting TGF-β and restoring E-cadherin expression in vitro. Additionally, amentoflavone dramatically re-duced migration, invasion, and EMT in colorectal cancer by upregulating the expression of miR-16-5p, according to recent research [78]. Six well-known miRNAs of the miR-16 family, miR-15-a/B, miR-16-5p, miR-195, miR-424, and miR-497, have been extensively studied in a variety of cancers, and they are thought to act as tumor suppressors to slow the growth of tumors [79][80][81][82][83].…”

Amentoflavone reverses epithelial‐mesenchymal transition in hepatocellular carcinoma cells by targeting p53 signalling pathway axis

“… 16 Amentoflavone exerts antitumor effects by inhibiting colorectal cancer EMT through the miR‐16‐5p/HMGA2/β‐catenin pathway. 32 These studies provide a lot of evidence that Amentoflavone is a potentially effective multitargeting drug for the prevention and treatment of a variety of cancers. Amentoflavone has a series of molecular targets and the underlying mechanisms are mainly through regulating the expression of different genes involved in cancer cell growth, cell cycle, apoptosis, autophagy, metastasis, angiogenesis, epigenetic modification, etc.…”