LncRNA MALAT1 promotes migration and invasion of non-small-cell lung cancer by targeting miR-206 and activating Akt/mTOR signaling

Abstract

Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) functions as a crucial regulator of metastasis in lung cancer. The aim of this study is to unravel the underlying mechanisms of lncRNA MALAT1 in non-small-cell lung cancer (NSCLC). A cohort of 36 NSCLC tumor tissues and adjacent normal tissues was collected postoperatively from patients with NSCLC. qRT-PCR was performed to detect the expression of MALAT1 in both NSCLC tissues and cell lines. Cell migration and invasion were monitored by wound healing assay and transwell invasion assay. Western blot was used to detect the expression levels of epithelial-mesenchymal transition proteins and Akt/mTOR key components after treatment. Dual luciferase reporter assay coupled with qRT-PCR was used to verify the direct interaction between MALAT1 and miR-206. MALAT1 was significantly up-regulated in both NSCLC tissues and cell lines. High expression of MALAT1 correlated positively with tumor size and lymphatic metastasis in NSCLC, whereas no correlation was found between MALAT1 expression and sex, age, clinical stage, and histological grade. We also showed that MALAT1 promoted epithelial-mesenchymal transition, cell migration, and invasion by activating Akt/mTOR signaling in A549 and H1299 cells. miR-206 was a direct downstream target of MALAT1 in NSCLC. MALAT1 promoted cell migration and invasion by sponging miR-206 in NSCLC cells. In addition, miR-206 inhibited MALAT1-mediated activation of Akt/mTOR signaling in A549 and H1299 cells. lncRNA MALAT1 promotes migration and invasion of NSCLC by targeting miR-206 and activating Akt/mTOR signaling.

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

“…But as to one LncRNA, the molecular mechanism may contain many aspects. For example, LncRNA‐MALAT1, which is highly conserved among mammals, could not only competitively bind with miR‐145‐5p, miR‐204 and miR‐206 as a ceRNA, but also activate Akt/mTOR signalling pathway in order to induce the metastasis of NSCLC . The same LncRNA may have different molecular mechanism in diverse tumours.…”

“…For example, LncRNA-MALAT1, which is highly conserved among mammals, could not only competitively bind with miR-145-5p, 121 miR-204 122 and miR-206 123 as a ceRNA, but also activate Akt/mTOR signalling pathway in order to induce the metastasis of NSCLC. 123 The same LncRNA may have different molecular mechanism in diverse tumours. But until now, the studies in LncRNAs are only at the experimental level.…”

Increased miR‐323a induces bladder cancer cell apoptosis by suppressing c‐Met

“…In recent years, more and more evidences have shown that miRNA plays a key regulatory role in tumorigenesis and development . For instance, miRNAs are found to affect cell differentiation, proliferation, and apoptosis by reducing the stability of target genes or inhibiting their translation . Exploring the relationship between miRNAs and BC formation provides a new way to define the pathogenic factors of BC.…”

Current Landscape of Epigenetics in Lung Cancer: Focus on the Mechanism and Application

“…Changes in these epigenetic factors result in the dysregulation of key oncogenes and tumor suppressor genes [18,19]. Many of the epigenetic events in lung cancer affect cancer hallmarks, such as proliferation [20][21][22][23], invasion [24][25][26], metastasis [27][28][29][30][31][32][33], apoptosis [34][35][36][37], and cell cycle regulation. In addition to cancer hallmarks, several important signaling pathways are affected by epigenetic deregulation in lung cancer, such as the ERK family, the NF-kB signaling pathway, and the Hedgehog signaling pathway [18].…”