lncDILC Downregulation in Liver Cancer-Associated Fibroblasts Drives Pro-Invasive Conversion via a miR-6071-ZNF395
Yawen Li1, Jilong Liu1, Shentao Tai1
1Department of Gastroenterology, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Cancer Science
|October 30, 2025
Summary
A novel pathway involving long non-coding RNA DILC (lncDILC) suppresses cancer-associated fibroblast (CAF) conversion in liver cancer. This discovery offers potential new therapeutic targets for treating hepatocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cancer-associated fibroblasts (CAFs) drive hepatocarcinoma progression.
- The mechanisms behind normal fibroblast (NF) to CAF transformation are unclear.
- Long non-coding RNA DILC (lncDILC) is downregulated in liver cancer.
Purpose of the Study:
- To investigate the role of lncDILC in the conversion of NFs to CAFs.
- To elucidate the molecular mechanism of lncDILC in hepatocarcinoma.
- To identify potential therapeutic targets for liver cancer treatment.
Main Methods:
- Quantitative real-time PCR to measure lncDILC expression.
- Knockdown and overexpression experiments in NFs and CAFs.
- Cell migration and invasion assays.
- MiRNA target prediction and validation.
- Western blotting to assess protein levels.
Main Results:
- lncDILC was significantly downregulated in liver cancer CAFs compared to NFs.
- lncDILC knockdown promoted NF to CAF conversion and enhanced cancer cell invasion.
- lncDILC overexpression in CAFs reduced their invasiveness and suppressed metastasis.
- lncDILC targets miR-6071, which suppresses zinc finger protein 395 (ZNF395).
- ZNF395 overexpression reversed the pro-invasive effects of lncDILC knockdown.
Conclusions:
- A novel lncDILC-miR-6071-ZNF395 pathway suppresses fibroblast to CAF conversion.
- This pathway highlights lncDILC as a potential tumor suppressor in hepatocarcinoma.
- The identified pathway provides new therapeutic targets for liver cancer treatment.
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