Neoplasma Vol.70, No.4, p. 526–533, 2023
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| Title: LncRNA HIF1A-AS2 mediates imatinib resistance by regulating autophagy in gastrointestinal stromal tumor cells |
| Author: Jingyi Yan, Xiaolei Chen, Ji Lin, Xuecheng Sun, Wei Chen |
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Abstract: The aim of this study was to explore the role and mechanism of long non-coding RNA (lncRNA) HIF1A antisense RNA 2 (HIF1A-AS2) in regulating imatinib (IM) resistance in gastrointestinal stromal tumor (GIST) cells under hypoxia. The expression of HIF1A-AS2 was silenced by siRNA in GIST cells. Cytotoxicity, apoptosis, and autophagy were evaluated under normoxic and hypoxic conditions. The expression levels of HIF1A-AS2, HIF1A, apoptosis-associated genes, and autophagy-associated genes were determined by qRT-PCR analysis and western blot. We found that lncRNA HIF1A-AS2 was highly expressed in GIST tissues and cells. Knockdown of HIF1A-AS2 increased the sensitivity of GIST cells to IM and increased apoptosis. Moreover, a hypoxic environment decreased the sensitivity of GIST cells to IM, and the knockdown of HIF1A-AS2 reversed this effect. Mechanistically, the knockdown of HIF1A-AS2 inhibited IM-mediated autophagy. Finally, HIF1A was found to positively regulate HIF1A-AS2 under hypoxic conditions. Collectively, these data demonstrate that hypoxia-induced HIF1A-AS2 promotes IM resistance in GIST cells by regulating autophagy.
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| Keywords: HIF1A-AS2; gastrointestinal stromal tumor; imatinib; autophagy |
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Published online: 03-Oct-2023
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| Year: 2023, Volume: 70, Issue: 4 |
Page From: 526, Page To: 533 |
doi:10.4149/neo_2023_230523N272
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