Cellular signalling · 2025
LncRNA AFAP1-AS1 promoting residual tumor progression after insufficient radiofrequency ablation by up-regulating macropinocytosis in hepatocellular carcinoma.
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Wei Qiuxia, Xiong Shiyu, Luo Wanrong, Zhang Qi, Zheng Sui, Luo Man, Tang Haifeng, Zhang Wenyue, Luo Baoming
Аннотация
BACKGROUND: The impact of macropinocytosis on residual tumor progression following insufficient radiofrequency ablation (IRFA) in hepatocellular carcinoma (HCC) remains uncertain.
OBJECTIVES: It is very important to further investigate the regulatory mechanism of macropinocytosis after IRFA in HCC.
METHODS: We established cellular and animal models of IRFA using heat-treated HCC cells and subcutaneous tumors. In addition, we evaluated macropinocytosis level via FITC-dextran uptake, analyzed RNA expression by RT-qPCR, assessed proteins expression through Western blot, and performed functional assays. We also explored 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, a pharmacological blocker of macropinocytosis) and LncRNA AFAP1-AS1 effects on tumor growth in animal models.
RESULTS: We demonstrated that IRFA increased macropinocytosis in both HCC cells and xenografted HCC tissues. EIPA markedly suppressed the proliferation, migration, and invasion of HCC cells and suppressed residual tumor growth. Furthermore, We found that AFAP1-AS1 expression was significantly elevated following IRFA in the tissues of HCC patients and HCC cell lines due to the increase in m6A modification. An increase in AFAP1-AS1 expression correlated with heightened macropinocytosis activity. Mechanistically, AFAP1-AS1 indirectly increased EGFR expression by interacting with and reducing the levels of miR-139-5p, thereby contributing to residual tumor progression post-IRFA through the upregulation of macropinocytosis.
CONCLUSIONS: Our findings revealed AFAP1-AS1's oncogenic role and proposed its potential as a diagnostic marker and therapeutic candidate for residual tumor progression and macropinocytosis suppression in HCC.
OBJECTIVES: It is very important to further investigate the regulatory mechanism of macropinocytosis after IRFA in HCC.
METHODS: We established cellular and animal models of IRFA using heat-treated HCC cells and subcutaneous tumors. In addition, we evaluated macropinocytosis level via FITC-dextran uptake, analyzed RNA expression by RT-qPCR, assessed proteins expression through Western blot, and performed functional assays. We also explored 5-(N-ethyl-N-isopropyl)-amiloride (EIPA, a pharmacological blocker of macropinocytosis) and LncRNA AFAP1-AS1 effects on tumor growth in animal models.
RESULTS: We demonstrated that IRFA increased macropinocytosis in both HCC cells and xenografted HCC tissues. EIPA markedly suppressed the proliferation, migration, and invasion of HCC cells and suppressed residual tumor growth. Furthermore, We found that AFAP1-AS1 expression was significantly elevated following IRFA in the tissues of HCC patients and HCC cell lines due to the increase in m6A modification. An increase in AFAP1-AS1 expression correlated with heightened macropinocytosis activity. Mechanistically, AFAP1-AS1 indirectly increased EGFR expression by interacting with and reducing the levels of miR-139-5p, thereby contributing to residual tumor progression post-IRFA through the upregulation of macropinocytosis.
CONCLUSIONS: Our findings revealed AFAP1-AS1's oncogenic role and proposed its potential as a diagnostic marker and therapeutic candidate for residual tumor progression and macropinocytosis suppression in HCC.