LncRNA MAFG-AS1 boosts the proliferation of lung adenocarcinoma cells via regulating miR-744-5p/MAFG axis.

Lung adenocarcinoma (LUAD) is typically featured by a low 5-year survival rate, hence there is a necessary to investigate new biomarkers in LUAD progression. Competing endogenous RNA (ceRNA) network has been widely reported in the regulation of tumor processes, which is also the main direction of this paper. Based on the data of GEPIA database, lncRNA MAFG-AS1 was upregulated in LUAD tissues, which was associated with poor prognosis of patients. Proliferation or apoptosis of LUAD cells were measured by CCK-8, EdU and caspase-3 activity assays followed by Western blot. The results indicated that silencing of MAFG-AS1 suppressed cell proliferation but induced cell apoptosis. RNA FISH staining showing the cytoplasmic localization of MAFG-AS1 in LUAD cells. Mechanism detection revealed that MAFG-AS1 served as a molecular sponge of miR-744-5p to upregulate its nearby gene MAF bZIP transcription factor G (MAFG) in LUAD cells. Functionally, MAFG overexpression attenuated the cellular processes mediated by MAFG-AS1 knockdown. In summary, this study unveiled the MAFG-AS1/miR-744-5p/MAFG axis in LUAD, providing a potent and promising therapeutic target for LUAD patients.

Sui Y ，Lin G ，Zheng Y ，Huang W ... -  《-》

LncRNA MAFG-AS1 Promotes Lung Adenocarcinoma Cell Migration and Invasion by Targeting miR-3196 and Regulating SOX12 Expression.

Lung adenocarcinoma (LUAD) patients exhibit poor prognosis, primarily due to metastasis. Emerging studies have demonstrated that long noncoding RNAs (lncRNAs) play critical roles in cancer progression and metastasis besides their physiological function. Here, we investigated the potential role of lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG-AS1) in LUAD metastasis by analyzing its expression in The Cancer Genome Atlas (TCGA) LUAD database, and its function in LUAD using in vitro and in vivo experiments. We performed bioinformatics analysis, western blotting, dual-luciferase reporter gene assay, RNA immunoprecipitation (RIP), and rescue assays to reveal the molecular mechanisms underlying MAFG-AS1 function. We observed augmented expression of MAFG-AS1 in LUAD tissues compared with normal adjacent tissues, and its association with poor prognosis. Furthermore, MAFG-AS1 overexpression promoted LUAD cell migration, proliferation, invasion, and epithelial mesenchymal transition (EMT). Besides, MAFG-AS1 also targeted miR-3196 directly by acting as an endogenous sponge, thereby rescuing the inhibition of SOX12, a target of miR-3196. Thus, the rescue assays demonstrated that MAFG-AS1 promotes cell migration, invasion, and EMT by modulating the miR-3196/SOX12 pathway. In conclusion, our findings suggest that MAFG-AS1/miR-3196/SOX12 axis regulates LUAD progression and is a potential therapeutic target for LUAD.

Wu Q ，Jiang J 《-》

Long noncoding RNA TMPO-AS1 promotes lung adenocarcinoma progression and is negatively regulated by miR-383-5p.

Long noncoding RNAs (lncRNAs) play critical roles in the pathogenesis of various diseases, including a variety of tumors. Nevertheless, its functional roles and underlying molecular basis for their dysregulation in lung adenocarcinoma (LUAD) are largely unknown. Herein, in our study, we identified that lncRNA TMPO-AS1 is significantly upregulated in LUAD tissues and cell lines. Knockdown of TMPO-AS1 remarkably suppressed LUAD cell growth, induced apoptosis as well as G1/S arrest, and inhibited LUAD cell invasion, whereas overexpression of TMPO-AS1 exerts the opposite effects. Next, we implemented online database analysis tools to find that mir-383-5p could target TMPO-AS1, and our data showed that TMPO-AS1 was negatively correlated with mir-383-5p in LUAD specimens. We found that inhibiting miR-383-5p expression led to a marked upregulation of TMPO-AS1 level, while overexpression of miR-383-5p markedly suppressed TMPO-AS1's expression and function, suggesting that TMPO-AS1 is negatively regulated by miR-383-5p. In addition, we confirmed that miR-383-5p directly targeted TMPO-AS1 by binding to microRNA binding sites in the TMPO-AS1 sequence with a luciferase reporter and RIP assays. Besides, the inhibition of TMPO-AS1 significantly suppressed the tumorigenesis ability of LUAD cells in vivo. Together, these results demonstrate that TMPO-AS1 could be considered as a potential therapeutic target for LUAD patients.

Mu X ，Wu H ，Liu J ，Hu X ，Wu H ，Chen L ，Liu W ，Luo S ，Zhao Y ... -  《-》

LncRNA GMDS-AS1 inhibits lung adenocarcinoma development by regulating miR-96-5p/CYLD signaling.

According to the global cancer statistic, lung cancer is one of the most dangerous tumors, which poses a serious threat to human health. Exploration the mechanism of lung cancer and new targeted therapeutic measures is always the hot topic. Long noncoding RNA (lncRNA) is an important factor affecting the development of tumors. However, the research on the mechanism of lncRNA in the progress of lung cancer needs to be further expanded. In this study, we found that the expression of lncRNA GMDS-AS1 was significantly reduced in lung adenocarcinoma (LUAD) tissues and cells. Upregulated GMDS-AS1 can significantly inhibit the proliferation of LUAD cells and promote cell apoptosis in vitro and in vivo. The results indicate that GMDS-AS1 acts as a tumor suppressor gene to affect the development of LUAD. Further studies revealed that GMDS-AS1 is a target gene of miR-96-5p, and GMDS-AS1 regulates proliferation and apoptosis of LUAD cells in association with miR-96-5p. In addition, we also confirmed that CYLD lysine 63 deubiquitinase (CYLD) is also a target gene of miR-96-5p. Through various validations, we confirmed that GMDS-AS1 can act as a ceRNA to upregulate the expression of CYLD by sponging miR-96-5p. Moreover, the intervention of GMDS-AS1/miR-96-5p/CYLD network can regulate the proliferation and apoptosis of LUAD cells. In this study, we revealed that the GMDS-AS1/miR-96-5p/CYLD network based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for targeted therapy of LUAD.

Zhao M ，Xin XF ，Zhang JY ，Dai W ，Lv TF ，Song Y ... -  《Cancer Medicine》

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5.

Jia Y ，Duan Y ，Liu T ，Wang X ，Lv W ，Wang M ，Wang J ，Liu L ... -  《Cell Death & Disease》