HAND2-AS1 Promotes Ferroptosis to Reverse Lenvatinib Resistance in Hepatocellular Carcinoma by TLR4/NOX2/DUOX2 Axis
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
INTRODUCTION: Lenvatinib resistance causes less than 40% of the objective response rate. Therefore, it is urgent to explore new therapeutic targets to reverse the lenvatinib resistance for HCC. HAND2-AS1 is a critical tumor suppressor gene in various cancers.
METHODS: Here, we investigated the role of HAND2-AS1 in the molecular mechanism of lenvatinib resistance in HCC. It was found that HAND2-AS1 was lowly expressed in the HepG2 lenvatinib resistance (HepG2-LR) cells and HCC tissues and associated with progression-free intervals via TCGA. Overexpression of HAND2-AS1 (OE-HAND2-AS1) decreased the IC50 of lenvatinib in HepG2-LR cells to reverse lenvatinib resistance. Moreover, OE-HAND2-AS1 induced intracellular concentrations of malondialdehyde (MDA) and lipid ROS and decreased the ratio of glutathione to glutathione disulfide (GSH/GSSG) to promote ferroptosis.
RESULTS: A xenograft model in which nude mice were injected with OE-HAND2-AS1 HepG2-LR cells confirmed that OE-HAND2-AS1 could reverse lenvatinib resistance and decrease tumor formation in vivo. HAND2-AS1 promoted the expression of ferroptosis-related genes (TLR4, NOX2, and DUOX2) and promoted ferroptosis to reverse lenvatinib resistance by increasing TLR4/ NOX2/DUOX2 via competing endogenous miR-219a-1-3p in HCC cells. Besides, patients with a low HAND2-AS1 level had early recurrence after resection.
CONCLUSION: These findings suggested that HAND2-AS1 may be a potential therapeutic target and an indicator of early recurrence for HCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Current cancer drug targets - (2024) vom: 07. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Song, Zheng [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer |
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| Anmerkungen: |
Date Revised 11.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.2174/0115680096279597240219055135 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369551648 |
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| 245 | 1 | 0 | |a HAND2-AS1 Promotes Ferroptosis to Reverse Lenvatinib Resistance in Hepatocellular Carcinoma by TLR4/NOX2/DUOX2 Axis |
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| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a INTRODUCTION: Lenvatinib resistance causes less than 40% of the objective response rate. Therefore, it is urgent to explore new therapeutic targets to reverse the lenvatinib resistance for HCC. HAND2-AS1 is a critical tumor suppressor gene in various cancers | ||
| 520 | |a METHODS: Here, we investigated the role of HAND2-AS1 in the molecular mechanism of lenvatinib resistance in HCC. It was found that HAND2-AS1 was lowly expressed in the HepG2 lenvatinib resistance (HepG2-LR) cells and HCC tissues and associated with progression-free intervals via TCGA. Overexpression of HAND2-AS1 (OE-HAND2-AS1) decreased the IC50 of lenvatinib in HepG2-LR cells to reverse lenvatinib resistance. Moreover, OE-HAND2-AS1 induced intracellular concentrations of malondialdehyde (MDA) and lipid ROS and decreased the ratio of glutathione to glutathione disulfide (GSH/GSSG) to promote ferroptosis | ||
| 520 | |a RESULTS: A xenograft model in which nude mice were injected with OE-HAND2-AS1 HepG2-LR cells confirmed that OE-HAND2-AS1 could reverse lenvatinib resistance and decrease tumor formation in vivo. HAND2-AS1 promoted the expression of ferroptosis-related genes (TLR4, NOX2, and DUOX2) and promoted ferroptosis to reverse lenvatinib resistance by increasing TLR4/ NOX2/DUOX2 via competing endogenous miR-219a-1-3p in HCC cells. Besides, patients with a low HAND2-AS1 level had early recurrence after resection | ||
| 520 | |a CONCLUSION: These findings suggested that HAND2-AS1 may be a potential therapeutic target and an indicator of early recurrence for HCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Hepatocellular carcinoma | |
| 650 | 4 | |a cancer | |
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| 700 | 1 | |a Luo, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Caihong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Sihao |e verfasserin |4 aut | |
| 700 | 1 | |a He, Quanwei |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Ran |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Zhaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Xiujuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yongping |e verfasserin |4 aut | |
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