HIF1A-AS2 induces osimertinib resistance in lung adenocarcinoma patients by regulating the miR-146b-5p/IL-6/STAT3 axis
Si J., Ma Y., Lv C., Hong Y., Tan H., Yang Y.
Animal Study, published in Mol Ther Nucleic Acids (2021) — summary generated from the PubMed abstract.
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Animal Study
- Journal
- Mol Ther Nucleic Acids (2021)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 34703647
- PMCID
- PMC8517096
- DOI
- 10.1016/j.omtn.2021.09.003
- Citations
- 33
Abstract (original English)
Although epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) show efficacy in lung adenocarcinoma (LUAD) patients, TKI resistance inevitably develops, limiting long-term results. Thus, there is an urgent need to address drug resistance in LUAD. Long non-coding RNA (lncRNA) HIF1A-AS2 could be a critical mediator in the progression of various tumor types. We examined the function of HIF1A-AS2 in modifying tumor aggravation and osimertinib resistance in lung adenocarcinoma. Using clinical samples, we showed that HIF1A-AS2 was upregulated in LUAD specimens, predicting poorer overall survival and disease-free survival. HIF1A-AS2 silencing inhibited the proliferation, migration, and tumorigenesis of LUAD cells and therapeutic efficacy of osimertinib against tumor cells in vitro and in vivo . RNA precipitation assays, western blotting, luciferase assays, and rescue experiments demonstrated that HIF1A-AS2 sponged microRNA-146b-5p (miR-146b-5p), promoting interleukin-6 (IL-6) expression, activating the IL-6/STAT3 pathway, and leading to LUAD progression. miR-146b-5p and IL-6 levels were correlated with the prognosis of LUAD patients. Our results indicated that HIF1A-AS2 functions as an oncogenic factor in adenocarcinoma cells by targeting the miR-146b-5p/IL-6/STAT3 axis and may be a prognostic indicator of survival. Moreover, it can be a potential therapeutic target to en
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
- • This is preclinical work; animal or laboratory results cannot be applied to humans.
Evidence level
Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.
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