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 enhance the efficacy of
osimertinib in LUAD patients.