Long non-coding RNA PVT1 contributes to cell growth and metastasis in non-small-cell lung cancer by regulating miR-361-3p/SOX9 axis and activating Wnt/β-catenin signaling pathway.

Lung cancer is the most frequent cause of cancer-related mortality in men, and 85 % of lung cancer is diagnosed as non-small-cell lung cancer (NSCLC). Plasmacytoma variant translocation1 (PVT1) serves as an oncogenic factor in NSCLC. However, the pathogenesis of PVT1 in NSCLC is still vague. The expression levels of PVT1, sex determining region Y (SRY)-related high mobility group (HMG)-box9 (SOX9), and microRNA (miR)-361-3p in NSCLC tissues and cells were detected by quantitative real-time polymerase chain reaction (RT-qPCR). The protein levels of SOX9, β-catenin, and c-Myc were detected by western blot assay. Cell proliferation, apoptosis, migration and invasion were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, transwell assays, severally. The interaction between miR-361-3p and PVT1 or SOX9was predicted by starBase, and then verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. PVT1 and SOX9 was highly expressed in NSCLC tumor tissues and cells. PVT1 facilitated proliferation, migration, invasion and hindered apoptosis of NSCLC cells. MiR-361-3p was a target of PVT1 in NSCLC cells. SOX9 acted as a target of miR-361-3p. PVT1 worked as a miR-361-3p sponge to regulate SOX9 expression. PVT1 modulate the Wnt/β-catenin Signaling Pathway by miR-361-3p/SOX9 axis. Our studies disclosed that PVT1 boosted proliferation, migration, invasion and curbed apoptosis by miR-361-3p/SOX9 axis, providing the possible therapeutic strategy for NSCLC.

Qi G ，Li L 《-》

Upregulated lncRNA SNHG1 contributes to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway.

Cui Y ，Zhang F ，Zhu C ，Geng L ，Tian T ，Liu H ... -  《Oncotarget》

Overexpression of HIF-2α-Dependent NEAT1 Promotes the Progression of Non-Small Cell Lung Cancer through miR-101-3p/SOX9/Wnt/β-Catenin Signal Pathway.

The present study aimed to explore the function of NEAT1 on non-small cell lung cancer (NSCLC), as well as its underlying mechanisms. Quantitative realtime PCR (qRT-PCR) was used to measure NEAT1 expression in NSCLC tissues and cells. MTT assay and transwell assay were performed to detect cell proliferation, migration and invasion. Potential target genes were identified via luciferase reporter assay. Protein analysis was performed through western blotting. The expressions of NEAT1 were significantly higher in both of NSCLC tissues and cells than in normal controls. High expression of NEAT1 was significantly associated with TNM stage (P=0.000) and metastasis (P=0.000). NEAT1 knockdown inhibited the proliferation, migration and invasion of NSCLC cells. Hypoxia induction mediated by HIF-2α promoted EMT and NEAT1 expressions. Moreover, miR-101-3p was a target of NEAT1. We also found that SOX9 was a target of miR-101-3p. Oncogenic function of NEAT1 on NSCLC progression was mediated by miR-101-3p/SOX9/Wnt/β-catenin signaling pathway. NEAT1 up-regulation induced by HIF-2α over-expression could promote the progression of NSCLC under hypoxic condition. Moreover, NEAT1 also takes part in NSCLC progression via miR-101-3p/SOX9/Wnt/β-catenin axis.

Kong X ，Zhao Y ，Li X ，Tao Z ，Hou M ，Ma H ... -  《-》

The long non-coding RNA PVT1/miR-145-5p/ITGB8 axis regulates cell proliferation, apoptosis, migration and invasion in non-small cell lung cancer cells.

Wei CM ，Zhao XF ，Qiu HB ，Ming Z ，Liu K ，Yan J ... -  《NEOPLASMA》

Knockdown of LncRNA PVT1 inhibits tumorigenesis in non-small-cell lung cancer by regulating miR-497 expression.

Plasmacytoma variant translocation1 (PVT1) was reported to be upregulated in non-small-cell lung cancer (NSCLC) tissues, serve as a promising biomarker for diagnosis and prognosis of NSCLC, and promoted NSCLC cell proliferation. However, the detailed molecular mechanism of PVT1 involved in the pathogenesis and development of NSCLC remains largely unknown. In this study, the expression levels of PVT1 and miR-497 in NSCLC cells were determined by qRT-PCR. Cell viability, invasion and apoptosis were detected by MTT assay, cell invasion assay and flow cytometry analysis, respectively. RNA immunoprecipitation (RIP) and luciferase reporter assay were performed to confirm whether PVT1 directly interacts with miR-497. A xenograft mouse model was established to confirm the effect of PVT1 on tumor growth in vivo and the underlying molecular mechanism. Our findings indicated that PVT1 was significantly upregulated and miR-497 was markedly downregulated in NSCLC cell lines. si-PVT1 effectively decreased the expression of PVT1 and increased the expression of miR-497. PVT1 knockdown remarkably inhibited cell viability, invasion and promoted apoptosis in NSCLC cells. RIP and luciferase reporter assay demonstrated that PVT1 could directly interact with miR-497. Moreover, PVT1 overexpression reversed the inhibitory effect of miR-497 on cell viability, invasion and promotion effect on apoptosis of NSCLC cells. Furthermore, in vivo experiment showed that knockdown of PVT1 inhibited tumor growth in vivo and promoted miR-497 expression. In conclusion, knockdown of PVT1 inhibited cell viability, invasion and induced apoptosis in NSCLC by regulating miR-497 expression, elucidating the molecular mechanism of the oncogenic role of PVT1 in NSCLC and providing an lncRNA-directed target for NSCLC.

Guo D ，Wang Y ，Ren K ，Han X ... -  《-》