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Echinacoside inhibits hepatocellular carcinoma progression by targeting the miR-30c-5p/FOXD1/KLF12 axis
Guoyu Wang1,1, Yang Han1,1, Juhua Zhuang1
1Department of Nuclear Medicine, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Background:
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-attributed mortality and the primary liver malignancy in the world. Echinacoside is a phenylethanoid glycoside derived from traditional Chinese medicinal herbs which possessed multiple health benefits on humans, including anti-tumor effects.
Objective:
This study aimed to demonstrate the function of echinacoside in HCC progression and the involvement of miR-30c-5p/FOXD1/KLF12 axis.
Methods:
The HepG2 cells were treated by different dose of echinacoside, miR-30c-5p mimic, miR-30c-5p inhibitor, and FOXD1 overexpression lentiviruses or siRNA individually or simultaneously. The cell invasion and migration were measured by transwell assay. RNA and protein levels were tested by RT-PCR and western blot, respectively. The regulatory function of miR-30c-5p on Forkhead box D1 (FOXD1), FOXD1 on Krüppel-like factor 12 (KLF12) was tested by luciferase reporter assay or/and ChIP assay. Meanwhile, a liver cancer lung metastasis mice model was used to examine the functions of echinacoside and miR-30c-5p on HCC metastasis in vivo. Moreover, the correlations among miR-30c-5p, FOXD1, KLF12, and HCC prognosis was analyzed using clinical sample and TCGA database.
Results:
Based on both in vitro and in vivo investigations, we found that echinacoside could inhibit HCC cell migration, invasiveness, and tumor metastasis, and associated with the enhanced miR-30c-5p/FOXD1/KLF12 axis. Furthermore, through analyzing the interactions among intermediate molecules, we revealed that miR-30c-5p, FOXD1, and KLF12üere clinically relevant with each other in HCC patients, correlated with HCC prognosis, and regulated by echinacoside to contribute in the inhibition of HCC progression.
Conclusions:
These findings suggest that echinacoside could inhibit HCC progression, and the mechanism related to the enhanced miR-30c-5p/FOXD1/KLF12 axis. Moreover, the abovementioned intermediate molecules might serve as prospective biomarkers for HCC prognosis.
Insights
Echinacoside inhibits hepatocellular carcinoma (HCC) progression by enhancing the miR-30c-5p/FOXD1/KLF12 pathway. This natural compound shows promise for treating liver cancer and offers potential biomarkers for prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide.
- Echinacoside, a compound from traditional Chinese medicine, exhibits anti-tumor properties.
Purpose of the Study:
- To investigate echinacoside's role in HCC progression.
- To elucidate the involvement of the miR-30c-5p/FOXD1/KLF12 axis in echinacoside's anti-cancer effects.
Main Methods:
- In vitro studies using HepG2 cells treated with echinacoside and related molecules.
- In vivo experiments utilizing a liver cancer lung metastasis mouse model.
- Analysis of molecular interactions, gene/protein expression, and clinical data.
Main Results:
- Echinacoside inhibited HCC cell migration, invasion, and metastasis in vitro and in vivo.
- The study identified an enhanced miR-30c-5p/FOXD1/KLF12 axis associated with echinacoside treatment.
- Clinical data and TCGA analysis confirmed the relevance of this axis in HCC prognosis.
Conclusions:
- Echinacoside suppresses HCC progression via the miR-30c-5p/FOXD1/KLF12 pathway.
- The miR-30c-5p/FOXD1/KLF12 axis represents a potential therapeutic target and prognostic biomarker for HCC.
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