MALAT1 Promotes Cell Tumorigenicity Through Regulating miR-515-5p/EEF2 Axis in Non-Small Cell Lung Cancer.

Abstract

BACKGROUND:

Previous studies suggested long noncoding RNA metastasis associated with lung adenocarcinoma transcript 1 (lncRNA MALAT1) acted as a tumor promoter to promote cell carcinogenesis in non-small cell lung cancer (NSCLC). MALAT1 was found to exist in serum exosomes of several cancers. However, the role of exosomal-derived MALAT1 in NSCLC remains poorly understood.

MATERIALS AND METHODS:

Exosomes were isolated using the ExoQuick precipitation kit. Western blot was used to detect the protein expression of CD3, CD63, apoptosis- and metastasis-related protein. The expression of MALAT1, microRNA (miR)-515-5p and eukaryotic elongation factor 2 (EEF2) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability, apoptosis, or invasion were measured using 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay, flow cytometry or transwell assay, respectively. The interaction between miR-515-5p and MALAT1 or EEF2 was confirmed by dual-luciferase reporter assay. In vivo experiments were conducted through the murine xenograft model.

RESULTS:

MALAT1 was highly expressed in serum and cell exosomes from NSCLC patients. MALAT1 knockdown repressed cell proliferation, invasion and induced cell apoptosis in vitro as well as inhibited tumor growth in vivo in NSCLC. Subsequently, we confirmed that MALAT1 was a sponge of miR-515-5p, and EEF2 was a target of miR-515-5p. Furthermore, MALAT1 served as a sponge of miR-515-5p to regulate EEF2 expression in NSCLC cells. More importantly, MALAT1 deletion  performed anti-tumor effects by interacting with miR-515-5p/EEF2 axis in vitro and in vivo in NSCLC.

CONCLUSION:

MALAT1 knockdown repressed NSCLC tumorigenicity by inhibiting cell proliferation, invasion and promoting apoptosis through regulating miR-515-5p/EEF2, besides, MALAT1 was highly enriched in exosomes of NSCLC, suggesting a possible molecular-targeted therapy for NSCLC patients.

• Authors: Feng Rong, Liang Liu, Can Zou, Jing Zeng, Yasheng Xu
• Journal: Cancer management and research (Cancer Manag Res) Vol. 12 Pg. 7691-7701 ( 2020) ISSN: 1179-1322 [Print] New Zealand
• PMID: 32943920 (Publication Type: Journal Article)
• Copyright: © 2020 Rong et al.