The lncRNA ELF3-AS1/miR-148b-3p/HMGB3 axis facilitates the progression of lung adenocarcinoma

Abstract Emerging evidence has established that long non-coding RNAs can serve as pivotal regulators of tumorigenesis across multiple cancer types. In the present study, the possible oncogenic role of E74-like ETS transcription factor 3-antisense RNA 1 (ELF3-AS1) in lung adenocarcinoma (LUAD) was assessed. Reverse transcription-quantitative PCR (RT-qPCR) analysis revealed significant upregulation of ELF3-AS1 in LUAD tissues compared with that in adjacent normal lung tissues. High ELF3-AS1 expression was found to be significantly associated with poorer overall survival rates and recurrence-free survival rates. To investigate its functional relevance, ELF3-AS1 expression was silenced in LUAD cell lines using small interfering RNA (siRNA). Subsequent functional assays demonstrated that ELF3-AS1 knockdown markedly suppressed malignant phenotypes. Specifically, Cell Counting Kit-8 assays revealed attenuated proliferation, whilst wound healing and Transwell assays uncovered impaired migratory and invasive capacities. Consistent with in vitro findings, xenograft models established by the subcutaneous injection of ELF3-AS1-depleted LUAD cells into nude mice exhibited significantly reduced tumor growth rates and final tumor weights compared with those in the control groups. Mechanistically, bioinformatics prediction using TargetScan and miRanda combined with dual-luciferase reporter assays identified a competitive endogenous RNA network whereby ELF3-AS1 can directly bind to microRNA (miR)-148b-3p, in turn reversing its inhibition of downstream target High-mobility group box 3 (HMGB3). Rescue experiments further confirmed that miR-148b-3p inhibition partially reversed the tumor-suppressive effects of ELF3-AS1 silencing. Collectively, these findings suggest a novel ELF3-AS1/miR-148b-3p/HMGB3 regulatory axis driving LUAD progression, positioning ELF3-AS1 as a potential therapeutic target and prognostic biomarker.