Journal
FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.796839
Keywords
the factor that binds to inducer of short transcripts-1; advanced hepatocellular carcinoma; microRNA; HIF-1 alpha; aerobic glycolysis; Warburg effect; molecular targeted agents resistance
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The transcription suppressor factor FBI-1 plays a crucial role in regulating hepatocellular carcinoma (HCC), by promoting the Warburg effect and enhancing resistance to molecular targeted agents in HCC cells. Through modulation of the miR-30c/HIF-1α pathway, FBI-1 promotes the Warburg effect and resistance to targeted agents.
The transcription suppressor factor FBI-1 (the factor that binds to inducer of short transcripts-1) is an important regulator of hepatocellular carcinoma (HCC). In this work, the results showed that FBI-1 promoted the Warburg effect and enhances the resistance of hepatocellular carcinoma cells to molecular targeted agents. Knockdown of FBI-1 via its small-interfering RNA (siRNA) inhibited the ATP level, lactate productions, glucose uptake or lactate dehydrogenase (LDH) activation of HCC cells. Transfection of siFBI-1 also decreased the expression of the Warburg-effect-related factors: hypoxia-inducible factor-1 alpha (HIF-1 alpha), lactate dehydrogenase A (LDHA), or GLUT1, and the epithelial-mesenchymal transition-related factors, Vimentin or N-cadherin. The positive correlation between the expression of FBI-1 with HIF-1 alpha, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1 alpha by binding to the 3 '-untranslated region (3 '-UTR) of HIF-1 alpha in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1 alpha and HIF-1 alpha pathway's activation by repressing the expression of miR. By modulating the miR-30c/HIF-1 alpha, FBI-1 promoted the Warburg effect or the epithelial-mesenchymal transition of HCC cells and promoted the resistance of HCC cells to molecular targeted agents.
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