<p>Long non-coding RNA (lncRNA) antisense RNA 1 (LOXL1-AS1), reportedly, exerts carcinogenic effects in cancers including non-small cell lung cancer (NSCLC) via competitive endogenous RNA (ceRNA) mechanism. Additionally, previous studies have implied that microRNA-122-5p (miR-122-5p) and E2F transcription factor 3 (E2F3) have cancer-promoting properties and tumor-suppressive properties, respectively. Here we aim to further explore the function and mechanism of LOXL1-AS1 in NSCLC. In this experimental study, we found that LOXL1-AS1 was high expression in NSCLC tissues and cell lines. High LOXL1-AS1 expression was significantly relevant to the advanced tumor node metastasis (TNM) stage and positive lymph node metastasis of NSCLC patients. LOXL1-AS1 overexpression promoted proliferation, migration and invasion of NSCLC cells, while LOXL1-AS1 knockdown had the opposite effect. LOXL1-AS1 could sponge miR-122-5p. E2F3 was a downstream target of miR-122-5p. LOXL1-AS1 increased E2F3 expression through repressing miR-122-5p. In addition, miR-122-5p up-regulation or E2F3 knockdown could offset the promoting effect of LOXL1-AS1 overexpression on proliferation, migration and invasion of NSCLC cells. Overall, this study demonstrates that LOXL1-AS1 promotes NSCLC cell proliferation and migration in vitro, and correlates with poor clinical outcomes, partially via modulating miR-122-5p/E2F3 axis.</p>