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

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 metastasisrelated 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.

si‑MALAT1 attenuates thymic cancer cell proliferation and promotes apoptosis via the miR‑145‑5p/HMGA2 pathway

“…In future studies, the effect of MALAT1 should be further examined using in vivo experiments. Rong et al ( 33 ) observed that MALAT1-knockdown repressed NSCLC tumorigenicity by inhibiting cell proliferation and invasion, and promoting apoptosis via regulating miR-515-5p/EEF2. Although the types of tumor cells investigated in the present study were not consistent with the aforementioned study, the current results confirmed those of the study by Rong et al ( 33 ).…”

“…Rong et al ( 33 ) observed that MALAT1-knockdown repressed NSCLC tumorigenicity by inhibiting cell proliferation and invasion, and promoting apoptosis via regulating miR-515-5p/EEF2. Although the types of tumor cells investigated in the present study were not consistent with the aforementioned study, the current results confirmed those of the study by Rong et al ( 33 ). The present study focused on thymic cancer, which is rarer in clinical practice, and the current results may therefore have a high clinical value and may provide a possible molecular-targeted therapy for patients with thymic cancer.…”

Proteome of actin stress fibers

“…In recent studies, eEF2 has increasingly been implicated in neurosynaptic plasticity (Verpelli et al ., 2010), NF-κB-associated innate immune response network (Bianco et al ., 2019), and tumor progression as an oncogene (Oji et al ., 2014; Sun et al ., 2015; Rong et al ., 2020). While the relevance of eEF2 to the cytoskeleton remains poorly elucidated, these discoveries may suggest its role in cytoskeletal regulation.…”

“…The copyright holder for this preprint this version posted June 1, 2021. ; https://doi.org/10.1101/2021.06.01.446528 doi: bioRxiv preprint Rong et al, 2020). While the relevance of eEF2 to the cytoskeleton remains poorly elucidated, these discoveries may suggest its role in cytoskeletal regulation.…”

Novel Insights Into MALAT1 Function as a MicroRNA Sponge in NSCLC

“…Rong et al found that the levels of MALAT1 in serum exosomes were higher in patients with NSCLC, suggesting that exosome-derived MALAT1 may also reflect the biological changes of NSCLC cells (49). Zhang et al found that the expression of MALAT1 in serum exosomes of NSCLC patients was upregulated and that the level of exosomal MALAT1 was positively correlated with tumor stage and lymph node metastasis (67).…”