Long non-coding RNA LOXL1 antisense RNA 1 promotes the malignancy of non-small cell lung cancer cells via modulating the microRNA-122-5p/E2F transcription factor 3 axis.

Zhijian Wang, Zhenkui Zhang, Liqiang Zhao, Aiwen Sun, Min Wang

Journal: Molecular genetics and genomics : MGG 2026;301(1):

PMID: 42484731

Abstract

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.

Address: Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100043, China.; Department of Laboratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100043, China.; Department of Respiratory Medicine, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No. 5, Beixiange, Xicheng District, Beijing, 100053, China. [email protected].

DOI: 10.1007/s00438-026-02485-1

MeSH Terms: Humans, MicroRNAs, Carcinoma, Non-Small-Cell Lung, Gene Expression Regulation, Neoplastic, E2F3 Transcription Factor, Lung Neoplasms, RNA, Long Noncoding, Cell Proliferation, Cell Movement, Cell Line, Tumor, Female, Male, Middle Aged, RNA, Antisense, RNA, Competitive Endogenous, Amino Acid Oxidoreductases