<p>LncRNA MALAT1 Aggravates the Progression of Non-Small Cell Lung Cancer by Stimulating the Expression of COMMD8 via Targeting miR-613</p>

Abstract

Background Non-small cell lung cancer (NSCLC) is a common malignant tumor in humans. Long non-coding RNA (lncRNA) involved in cancer progression has been reported frequently. The objective of this study was to investigate the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and explore a novel mechanism in NSCLC development. Materials and Methods The expression of MALAT1, copper metabolism MURR1 domain-containing 8 ( COMMD8 ) and microRNA-613 (miR-613) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of COMMD8, Cyclin D1, Ki67, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax), lactate dehydrogenase A (LDHA), CD63 and CD81 were determined by Western blot. Cell proliferation, the number of colonies and cell apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation and flow cytometry assays, respectively. Glycolysis was distinguished based on glucose consumption, lactate production and LDHA activity. The role of MALAT1 in vivo was verified by animal experiments. The relationship between miR-613 and MALAT1 or COMMD8 was predicted by the bioinformatics tool starbase and verified by dual-luciferase reporter assay. The exosomes were isolated using the corresponding kit and identified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Results MALAT1 and COMMD8 were aberrantly upregulated in NSCLC tissues and cells. MALAT1 or COMMD8 knockdown blocked cell proliferation, colony formation and glycolysis but accelerated cell apoptosis in vitro. Besides, MALAT1 knockdown reduced tumor growth in vivo. We found that miR-613 was a target of MALAT1, and miR-613 could bind to the 3ʹ untranslated region (3ʹUTR) of COMMD8 . MALAT1 regulated the expression of COMMD8 by absorbing miR-613. Moreover, the extracellular MALAT1 was transmitted by wrapping into exosomes. Conclusion MALAT1 promoted malignant activities of NSCLC cells through targeting miR-613/ COMMD8 axis, and exosome-mediated transfer of NSCLC might be a novel approach for NSCLC treatment.

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

“…lncRNAs have previously been regarded as non-functional; however, a series of studies identified the critical actions of lncRNAs in fundamental biological mechanisms, such as differentiation, stress response, growth, immunity, inflammation and tumorigenesis (10)(11)(12). Numerous lncRNAs are differentially expressed in NSCLC, with a notable association with NSCLC genesis and progression (13)(14)(15). lncRNAs are involved in the modulation of pathological processes in NSCLC cells, where they execute anti-oncogenic or pro-oncogenic roles (16).…”

Involvement of Long Non-Coding RNAs in Glucose Metabolism in Cancer

“…MALAT1 knockdown decreases glucose consumption and lactate production. It mediates these effects by binding to miR-613 thereby inhibiting its interaction with copper metabolism MURR1 domain-containing 8 (COMMD8) [ 122 ]. Research on COMMD8 in cancers is scarce.…”

Long non‑coding RNA MCM3AP‑AS1 facilitates colorectal cancer progression by regulating the microRNA‑599/ARPP19 axis

“…Previous studies have demonstrated that lncRNAs exert their functions by sponging miRNAs to regulate mRNAs (25)(26)(27). The StarBase software predicted that ARPP19 was a direct target of miR-599 (Fig.…”