MicroRNA-142-3p/MALAT1 inhibits lung cancer progression through repressing β-catenin expression.

MALAT1 is well documented to be highly expressed in non-small cell lung cancer (NSCLC) and its overexpression closely associates the malignant phenotype of NSCLC cells and poor prognosis of NSCLC patients. MALAT1 is also identified to enhance β-catenin expression and under the negative regulation of miR-142-3p. However, the role of miR-142-3p/MALAT1/β-catenin in the occurrence and development of NSCLC remains unclear. The objective of this study was to explore it. The results showed that miR-142-3p expression was reduced in NSCLC tissues, while β-catenin and MALAT1 expression levels were elevated. MTT, transwell chamber, flow cytometry assays demonstrated that up-regulation of miR-142-3p with mimic transfection significantly inhibited the proliferation, migration and promoted the apoptosis of NSCLC H1299 cells, and induced a G0/G1 phase arrest and S phase reduction. Besides, miR-142-3p negatively decreased MALAT1 expression as detected by RT-PCR and luciferase reporter assays. Moreover, up-regulation of miR-142-3p decreased β-catenin expression through down-regulating MALAT1 in H1299 cells. And in vivo experiment showed that miR-142-3p up-regulation, as well as the knockdown of either β-catenin or MALAT1 significantly reduced the tumorigenesis of NSCLC cells. Taken together, our study makes clear that miR-142-3p functions as a tumor suppressor in NSCLC progression through inhibiting MALAT1/β-catenin signaling.

Liu J ，Tian W ，Zhang W ，Jia Y ，Yang X ，Wang Y ，Zhang J ... -  《-》

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 ... -  《-》

LncRNA MALAT1 Depressed Chemo-Sensitivity of NSCLC Cells through Directly Functioning on miR-197-3p/p120 Catenin Axis.

Yang T ，Li H ，Chen T ，Ren H ，Shi P ，Chen M ... -  《-》

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》

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 《-》