m6A-mediated lncRNA NEAT1 plays an oncogenic role in non-small cell lung cancer by upregulating the HMGA1 expression through binding miR-361-3p.

Lung cancer is the most common primary malignant tumor of the lung, and 85% of lung cancer is non-small cell lung cancer (NSCLC). The N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) have been widely reported to participate in the development of non-small cell lung cancer. However, the potential molecular mechanisms of m6A-regulated lncRNAs in NSCLC still need further investigation. The expression levels and the role of lncRNA NEAT1 in NSCLC tissues or cells were measured by RT-qPCR, Western blot, cell counting kit 8 (CCK-8), flow cytometry assay. RNA immunoprecipitation (RIP) was used to measure the levels of m6A modification of NEAT1. Bioinformatics analysis and dual-luciferase reporter gene assay were detected the relationship between miR-361-3p and NEAT1/HMGA1. Mouse xenograft tumor models were established to confirm the effects of lncRNA NEAT1 in vivo. In this study, we verified whether m6A-modified lncRNA nuclear enriched abundant transcript 1 (NEAT1) is involved in NSCLC progression via miR-361-3p/HMGA1 axis. Firstly, we found that lncRNA NEAT1 was upregulated in NSCLC, and was associated with a poor survival in NSCLC patients. Methyltransferase like 3 (METTL3)-mediated m6A modification stabilized and upregulated NEAT1 expression. Next, function experiment indicated that depletion of METTL3 and NEAT1 induced cell apoptosis and inhibited cell proliferation, epithelial-mesenchymal transition (EMT). Likewise, in vivo experiments further supported the oncogenic role of NEAT1 in NSCLC. In addition, the molecular mechanism was uncovered in our study, and we found that lncRNA NEAT1 promoted the expression of high-mobility group AT-hook 1 (HMGA1) by sponging miR-361-3p and then promoted tumorigenesis of NSCLC. In conclusion, our findings demonstrated that METTL3-mediated m6A modification accelerated NSCLC progression by regulating the NEAT1/miR-361-3p/HMGA1 axis, which provides important targets for the treatment of NSCLC.

Qi L ，Yin Y ，Sun M 《-》

Downregulation of NEAT1 Suppresses Cell Proliferation, Migration, and Invasion in NSCLC Via Sponging miR-153-3p.

Zhao L ，Bi M ，Zhang H ，Shi M ... -  《-》

LncRNA NEAT1 induces autophagy through the miR-128-3p/ADAM28 axis to suppress apoptosis of nonsmall-cell lung cancer.

This study aimed to identify the molecular mechanism underlying NEAT1 regulation of non-small-cell lung cancer (NSCLC) autophagy and apoptosis. The expression levels of NEAT1, miR-128-3p, and ADAM28 in NSCLC tissues and cells were examined using qRT-PCR. The relationships between NEAT1, miR-128-3p, and ADAM28 expression levels and prognosis of NSCLC patients were investigated using the Kaplan-Meier analysis method. The interactions between NEAT1, miR-128-3p, and ADAM28 were confirmed by dual-luciferase reporter assay or FISH assay. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry assays, respectively. Apoptosis and autophagy-related proteins Bax, cleaved caspase-3, cleaved caspase-9, Bcl-2, LC3, Beclin-1, and p62 were analyzed by western blotting. Finally, an in vivo NSCLC mouse xenograft model was established to confirm the in vitro data. We showed NEAT1 and ADAM28 expression levels were upregulated, while the miR-128-3p level was downregulated in NSCLC tissues and cells. NSCLC patients with high NEAT1 expression levels, low miR-128-3p levels, or high ADAM28 levels had significantly reduced overall survival times. Silencing of NEAT1 inhibited NSCLC cell autophagy and promoted apoptosis by sponging miR-128-3p. MiR-128-3p directly targeted ADAM28 and suppressed ADAM28 expression, which led to deactivation of the JAK2/STAT3 signaling pathway. Furthermore, ADAM28 overexpression attenuated miR-128-3p overexpression-induced apoptosis and autophagy inhibition in NSCLC by increasing the phosphorylation of JAK2 and STAT3. NEAT1 depletion or miR-128-3p overexpression inhibited autophagy and promoted apoptosis in vivo by suppressing ADAM28. In other word, silencing NEAT1 inhibited autophagy and then promoted NSCLC cell apoptosis by deactivating the JAK2/STAT3 signaling pathway through regulation of miR-128-3p/ADAM28 axis.

Xie Y ，Zheng ZW ，He HT ，Chang ZB ... -  《-》

LncRNA NEAT1 regulated cell proliferation, invasion, migration and apoptosis by targeting has-miR-376b-3p/SULF1 axis in non-small cell lung cancer.

Chen LM ，Niu YD ，Xiao M ，Li XJ ，Lin H ... -  《-》

LncRNA NEAT1 accelerates breast cancer progression through regulating miR-410-3p/ CCND1 axis.

Liu X ，Yao W ，Xiong H ，Li Q ，Li Y ... -  《-》