Long non-coding RNA XIST expedites lung adenocarcinoma progression through upregulating MDM2 expression via binding to miR-363-3p.

Lung adenocarcinoma (LAD) is a highly aggressive malignant tumor which threatens the health and life of the population. Long non-coding RNA X-inactive specific transcript (XIST) and mouse double minute clone 2 (MDM2) are connected with the tumorigenesis of LAD. Nevertheless, whether MDM2 is regulated by XIST has not previously been reported in LAD. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of XIST, microRNA-363-3p (miR-363-3p) and MDM2 in LAD tissues and cells. The proliferation, migration, invasion and apoptosis of LAD cells were determined by 3-(4, 5-dimethylthiazol-2-YI)-2, 5-diphenyltetrazolium bromide (MTT), transwell or flow cytometry assay, respectively. MDM2 protein level was detected using western blot analysis. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pulldown assay were performed to determine the interaction among XIST, miR-363-3p and MDM2. A xenograft tumor model was constructed to validate the effect of XIST on LAD cells in vivo. We found that XIST and MDM2 were remarkably elevated while miR-363-3p was reduced in LAD tissues and cells. Both XIST and MDM2 downregulation restrained proliferation, migration and invasion, and facilitated apoptosis of LAD cells in vitro. Importantly, XIST bound to miR-363-3p to modulate MDM2 expression in LAD cells. Moreover, miR-363-3p knockdown or MDM2 elevation reversed the effects of XIST downregulation on the proliferation, migration, invasion and apoptosis of LAD cells. Furthermore, XIST knockdown constrained tumor growth on LAD cells in vivo. XIST knockdown repressed proliferation, migration and invasion, and accelerated apoptosis of LAD cells by downregulating MDM2 expression via binding to miR-363-3p. Significant findings of the study XIST and MDM2 were abnormally enhanced in LAD tissues and cells. Both downregulation of XIST and MDM2 repressed proliferation, migration and invasion, and boosted apoptosis of LAD cells in vitro. XIST bound to miR-363-3p to regulate MDM2 expression in LAD cells. Downregulation of XIST impeded tumor growth on LAD cells in vivo. What this study adds This study confirmed that XIST was a potential target for inhibiting the development of LAD, and affords a possible strategy for the treatment of LAD in the future.

Rong H ，Chen B ，Wei X ，Peng J ，Ma K ，Duan S ，He J ... -  《-》

Downregulation of long non-coding RNA XIST inhibits cell proliferation, migration, invasion and EMT by regulating miR-212-3p/CBLL1 axis in non-small cell lung cancer cells.

Qiu HB ，Yang K ，Yu HY ，Liu M ... -  《-》

The knockdown of LncRNA AFAP1-AS1 suppressed cell proliferation, migration, and invasion, and promoted apoptosis by regulating miR-545-3p/hepatoma-derived growth factor axis in lung cancer.

Lung cancer is one of the most common human cancers. Long noncoding RNA AFAP1-AS1 (LncRNA AFAP1-AS1) and microRNA-545-3p (miR-545-3p) were reported to play important roles in lung cancer development. This study aimed to elucidate the functional mechanisms of AFAP1-AS1 and miR-545-3p in lung cancer. Quantitative real time polymerase chain reaction was carried out to determine the levels of AFAP1-AS1, miR-545-3p and hepatoma-derived growth factor (HDGF). Cell proliferation, apoptosis, migration and invasion were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, flow cytometry, and transwell migration and invasion assays, respectively. Furthermore, the interaction between miR-545-3p and AFAP1-AS1 or HDGF was predicted by bioinformatics analysis software starbase and confirmed by the dual luciferase reporter assay. Western blot assay was used to detect the protein level of HDGF. Besides, murine xenograft model was conducted through injecting A549 cells transfected with sh-AFAP1-AS1. The expression levels of AFAP1-AS1 and HDGF were increased, while miR-545-3p was decreased in lung cancer tissues and cells. AFAP1-AS1 knockdown suppressed lung cancer cell proliferation, migration, and invasion and induced apoptosis. Furthermore, AFAP1-AS1 mediated cell progression through regulating miR-545-3p expression. In addition, miR-545-3p negatively regulated the expression level of HDGF via binding 3'-untranslated region of HDGF. As expected, AFAP1-AS1 knockdown inhibited lung cancer progression via affecting miR-545-3p/HDGF axis. Besides, AFAP1-AS1 knockdown suppressed lung cancer tumor growth in vivo. Collectively, our results suggested that AFAP1-AS1 promoted the development of lung cancer via regulating miR-545-3p/HDGF axis, providing a potential target for the treatment of lung cancer.

Sun J ，Min H ，Yu L ，Yu G ，Shi Y ，Sun J ... -  《-》

LncRNA SNHG16 promotes non-small cell lung cancer development through regulating EphA2 expression by sponging miR-520a-3p.

Recent evidence has found that lncRNA small nucleolar RNA host gene 16 (SNHG16) was associated with cell carcinogenesis in NSCLC. Here, we further investigated the precise functions and mechanisms of SNHG16 in NSCLC progression. The expression of SNHG16, microRNA (miR)-520a-3p and EPH Receptor A2 (EphA2) was measured using quantitative real-time polymerase chain reaction and western blot, respectively. Cell proliferation was determined using 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay. The migrated and invaded cells were measured by Transwell assay. Flow cytometry was used to detect apoptotic cells. The interaction between miR-520a-3p and SNHG16 or EphA2 was confirmed using a dual-luciferase reporter assay. We found that SNHG16 was upregulated in NSCLC tissues and cell lines, knockdown of SNHG16 inhibited cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. MiR-520a-3p directly bound to SNHG16 and miR-520a-3p, and SNHG16 acted as a ceRNA in regulating EphA2 through competitively binding to miR-520a-3p. Additionally, rescue assay exhibited the anticancer activity mediated by SNHG16 knockdown on NSCLC could be reversed by miR-520a-3p inhibition or EphA2 overexpression. SNHG16 promoted NSCLC development by regulating the miR-520a-3p/EphA2 axis, suggesting novel insights for the pathogenesis of NSCLC and new potential therapeutic targets for the treatment of NSCLC. Knockdown of SNHG16 inhibited NSCLC cell proliferation, migration, invasion and induced apoptosis in vitro as well as suppressed tumor growth in vivo. SNHG16 directly interacted with miR-520a-3p. EphA2 was a target of miR-520a-3p. SNHG16 could regulate the expression of EphA2 by binding to miR-520a-3p. SNHG16 promoted NSCLC development by regulating the miR-520a-3p/EphA2 axis.

Yu L ，Chen D ，Song J 《-》

LncRNA NNT-AS1 promotes non-small cell lung cancer progression through regulating miR-22-3p/YAP1 axis.

Lung cancer is the leading cause of cancer-related mortality worldwide. Studies have demonstrated that long noncoding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 (NNT-AS1) functioned as an oncogene in most malignancies, including non-small cell lung cancer (NSCLC). This study aimed to investigate the underlying mechanisms of NNT-AS1 in NSCLC progression. The levels of NNT-AS1, miR-22-3p and Yes-associated protein (YAP1) were detected by qRT-PCR in NSCLC tissues and cells. Kaplan-Meier analysis was conducted to analyze the correlation between NNT-AS1 expression and overall survival of NSCLC patients. Cell proliferation was evaluated by MTT assay. Cell migration and invasion were assessed using transwell assay. The protein levels of YAP1 and EMT-related proteins were detected by western blot. The molecular mechanism was predicted by starBase2.0 and validated by dual-luciferase reporter assay or RNA pull-down assay. Xenograft analysis was carried out to analyze tumor growth in vivo. We found that the levels of NNT-AS1 and YAP1 were enhanced, while miR-22-3p expression was decreased in NSCLC tissues and cells. High NNT-AS1 expression was correlated with poor prognosis. NNT-AS1 knockdown impeded proliferation, migration, invasion and EMT of NSCLC cells. NNT-AS1 targeted miR-22-3p, and YAP1 was a target of miR-22-3p in NSCLC cells. Furthermore, NNT-AS1 facilitated the progression of NSCLC by regulating miR-22-3p/YAP1 axis. NNT-AS1 knockdown repressed tumor growth in vivo. NNT-AS1 facilitated proliferation, migration, invasion and EMT of NSCLC cells by sponging miR-22-3p and regulating YAP1 expression, which might provide a potential biomarker and therapeutic target for NSCLC.

He W ，Zhang Y ，Xia S 《-》