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》

PRKCZ-AS1 promotes the tumorigenesis of lung adenocarcinoma via sponging miR-766-5p to modulate MAPK1.

Wang M ，Liao Q ，Zou P 《-》

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》

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 LOXL1-AS1 regulates the tumorigenesis and development of lung adenocarcinoma through sponging miR-423-5p and targeting MYBL2.

Lung adenocarcinoma (LUAD) is the most common form of malignant tumor and closely correlated with high risk of death worldwide. Accumulating researches have manifested that long noncoding RNAs (lncRNAs) are deeply involved in the progression of multiple cancers. LncRNA LOXL1 antisense RNA 1 (LOXL1-AS1) was identified as an oncogene in several cancers, nonetheless, its biological effect and regulatory mechanism have not been explained in LUAD. Our present study suggested that LOXL1-AS1 expression was considerably increased in LUAD tissues and cells. Moreover, LOXL1-AS1 deficiency notably hampered cell proliferation and migration as well as dramatically facilitated cell apoptosis. Through molecular mechanism assays, LOXL1-AS1 was identified as a cytoplasmic RNA and acted as a sponge of miR-423-5p. Furthermore, MYBL2 was targeted and negatively modified by miR-423-5p. Rescue experiments revealed that MYBL2 knockdown could counteract miR-423-5p repression-mediated enhancement on the progression of LOXL1-AS1 downregulated LUAD cells. More importantly, MYBL2 was discovered to interact with LOXL1-AS1 promoter, indicating a positive feedback loop of LOXL1-AS1/miR-423-5p/MYBL2 in LUAD. These findings manifested the carcinogenic role of LOXL1-AS1 and LOXL1-AS1/miR-423-5p/MYBL2 feedback loop in LUAD, which could be helpful to explore effective therapeutic strategy for LUAD patients.

Li W ，Zhang B ，Jia Y ，Shi H ，Wang H ，Guo Q ，Li H ... -  《Cancer Medicine》