Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α
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 mo...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:6282388999ff4677996cf0ff462828102021-11-12T05:54:58ZKnockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α2234-943X10.3389/fonc.2021.796839https://doaj.org/article/6282388999ff4677996cf0ff462828102021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.796839/fullhttps://doaj.org/toc/2234-943XThe 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-1α), 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-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3′-untranslated region (3′-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway’s activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, 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.Juan LiuChao YangXiao-Mei HuangPan-Pan LvYa-Kun YangJin-Na ZhaoSi-Yuan ZhaoWan-Jun SunFrontiers Media S.A.articlethe factor that binds to inducer of short transcripts-1advanced hepatocellular carcinomamicroRNAHIF-1αaerobic glycolysis/Warburg effectmolecular targeted agents resistanceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
the factor that binds to inducer of short transcripts-1 advanced hepatocellular carcinoma microRNA HIF-1α aerobic glycolysis/Warburg effect molecular targeted agents resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
the factor that binds to inducer of short transcripts-1 advanced hepatocellular carcinoma microRNA HIF-1α aerobic glycolysis/Warburg effect molecular targeted agents resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Juan Liu Chao Yang Xiao-Mei Huang Pan-Pan Lv Ya-Kun Yang Jin-Na Zhao Si-Yuan Zhao Wan-Jun Sun Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α |
| description |
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-1α), 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-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3′-untranslated region (3′-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway’s activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, 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. |
| format |
article |
| author |
Juan Liu Chao Yang Xiao-Mei Huang Pan-Pan Lv Ya-Kun Yang Jin-Na Zhao Si-Yuan Zhao Wan-Jun Sun |
| author_facet |
Juan Liu Chao Yang Xiao-Mei Huang Pan-Pan Lv Ya-Kun Yang Jin-Na Zhao Si-Yuan Zhao Wan-Jun Sun |
| author_sort |
Juan Liu |
| title |
Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α |
| title_short |
Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α |
| title_full |
Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α |
| title_fullStr |
Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α |
| title_full_unstemmed |
Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α |
| title_sort |
knockdown of fbi-1 inhibits the warburg effect and enhances the sensitivity of hepatocellular carcinoma cells to molecular targeted agents via mir-3692/hif-1α |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/6282388999ff4677996cf0ff46282810 |
| work_keys_str_mv |
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