Related Experiment Video

Updated: Dec 29, 2025

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines
08:50

In Vitro Cultivation Techniques for Modeling Liver Organogenesis, Building Assembloids, and Designing Synthetic Tissues using Human Cell Lines

Published on: April 18, 2025

813

MiR-612 regulates invadopodia of hepatocellular carcinoma by HADHA-mediated lipid reprogramming

Yang Liu1,2, Li-Li Lu1, Duo Wen1,3

  • 1Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Journal of Hematology & Oncology
|February 9, 2020
PubMed
Abstract

Insights

MicroRNA-612 (miR-612) suppresses hepatocellular carcinoma (HCC) progression by targeting HADHA, reprogramming lipids, and inhibiting metastasis. Low miR-612 and high HADHA levels correlate with poor patient prognosis, highlighting miR-612 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNA-612 (miR-612) is known to inhibit epithelial-mesenchymal transition (EMT), stemness, and metastasis in hepatocellular carcinoma (HCC).
  • The precise biological roles and molecular mechanisms of miR-612 in HCC progression remain incompletely understood.

Purpose of the Study:

  • To elucidate the biological characteristics and clinical relevance of miR-612 in HCC.
  • To investigate the molecular mechanisms underlying miR-612's function in HCC progression, focusing on its downstream targets and metabolic reprogramming.

Main Methods:

  • RNA immunoprecipitation and sequencing (RIP-seq) to identify direct downstream targets of miR-612.
  • In vitro and in vivo models, including cell lines and human tissue chips, were used to study HCC progression.
  • Analysis of cellular metabolism, including oxygen consumption rates (OCR) and ATP levels, and lipid reprogramming pathways.

Main Results:

  • HADHA was identified as a direct downstream target of miR-612.
  • miR-612 suppressed HCC cell invasion and metastasis by reprogramming lipids, reducing invadopodia formation, and inhibiting Wnt/β-catenin-mediated EMT via HADHA-mediated cholesterol alteration.
  • Metabolic analysis revealed decreased OCR, acetyl CoA, and ATP levels in cells with miR-612 overexpression or HADHA knockdown.
  • High HADHA and low miR-612 expression in HCC patients correlated with poor overall survival.

Conclusions:

  • miR-612 suppresses invadopodia formation, EMT, and HCC metastasis through HADHA-mediated lipid reprogramming.
  • These findings offer novel insights into the role of miR-612 in regulating tumor progression and metastasis in HCC.
  • miR-612 and HADHA represent potential biomarkers and therapeutic targets for HCC.
Keywords:
Hepatocellular carcinomaInvadopodiaMetastasismiR-612β-Oxidation

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

9.3K
Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma07:47

Non-Invasive PET/MR Imaging in an Orthotopic Mouse Model of Hepatocellular Carcinoma

Published on: August 31, 2022

2.6K

Related Concept Videos

Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.1K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
9.7K