RESUMO
BACKGROUND CircPSMC3 has been reported to play important roles in the occurrence and development of cancer. However, the role of circPSMC3 in NSCLC (non-small cell lung cancer) and the underlying mechanisms remain unclear. MATERIAL AND METHODS The expression of circPSMC3 in NSCLC tissues was measured through qRT-PCR (quantitative real-time polymerase chain reaction). The effect of circPSMC3 on the invasion and migration of NSCLC cell line H1299 was determined through transwell invasion assay and wound healing assay. Dual-luciferase reporter assay was performed for exploring the regulatory interaction between circPSMC3, miR-182-5p, and NME2. RESULTS Compared with adjacent normal tissues, the expression of circPSMC3 in NSCLC tissues was decreased. Lower circPSMC3 expression was closely associated with lymph node metastasis and higher TNM stage in NSCLC patients. Biological function analysis suggested that circPSMC3 inhibits the invasion and migration of H1299 cells through upregulating the expression of NME2. Mechanistically, circPSMC3 sponges miR-182-5p to suppress the invasion and migration of NSCLC cells via upregulating NME2 expression. CONCLUSIONS CircPSMC3 inhibits the invasion and migration of NSCLC cells through the miR-182-5p/NME2 signaling pathway.
Assuntos
ATPases Associadas a Diversas Atividades Celulares/genética , Carcinoma Pulmonar de Células não Pequenas/genética , MicroRNAs/genética , Complexo de Endopeptidases do Proteassoma/genética , Células A549 , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/metabolismo , Nucleosídeo NM23 Difosfato Quinases/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Invasividade Neoplásica/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Transdução de Sinais/genéticaRESUMO
BACKGROUND Lung cancer is a common tumor. Non-small-cell lung cancer (NSCLC) accounts for over 85% of lung cancer and has a high degree of malignancy. Angiogenesis plays an important role in NSCLC progression. Some studies have found that PVT1 can promote angiogenesis in tumor tissues, but the role of PVT1 in angiogenesis in NSCLC, as well as the underlying mechanism, is unclear. MATERIAL AND METHODS To explore the role of PVT1 in NSCLC, qRT-PCR, Western blot, luciferase reporter assay, and ELISA were carried out for detecting the relationship among PVT1, miR-29c, and VEGF. Tube formation assay was used to assess the role of PVT1 in angiogenesis in NSCLC. RESULTS Our results showed that higher PVT1 was expressed in NSCLC and the elevated PVT1 was closely related to angiogenesis and poor prognosis in NSCLC. Further functional analysis showed that higher PVT1 expression could promote angiogenesis by regulating VEGF in NSCLC. Mechanistically, the luciferase reporter assay confirmed that VEGF was the targeted gene of miR-29c. In addition, we found that miR-29c is an inhibitory target of PVT1. CONCLUSIONS We found that PVT1 promotes angiogenesis through targeting the miR-29c/VEGF signaling pathway in NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células A549 , Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , RNA Longo não Codificante/genética , Transdução de SinaisRESUMO
Background: Non-small cell lung carcinoma (NSCLC) is a highly malignant tumor with a poor prognosis worldwide. Some studies have demonstrated that circular pleiotrophin (circPTN) plays critical roles in tumorigenesis and tumor development. However, little is known about the role of circPTN in NSCLC. Methods: The circPTN expression in human NSCLC tissues was measured via quantitative real-time polymerase chain reaction (qRT-PCR). The function and potential mechanisms of circPTN in NSCLC angiogenesis were also investigated. We aimed to explore the function and potential mechanisms and clinical significance of circPTN in NSCLC. Results: We first found that circPTN was markedly upregulated in NSCLC tissues. A higher circPTN level was closely associated with angiogenesis and significantly shorter overall survival in patients with NSCLC. We then found that circPTN promoted angiogenesis in NSCLC. More importantly, we found that circPTN facilitated angiogenesis by regulating the expression of LYRM5 in NSCLC. Mechanistically, LYRM5 could be a direct target of microRNA-595 (miR-595). Additionally, we demonstrated that circPTN upregulated LYRM5 expression by sponging miR-595, which promoted NSCLC angiogenesis in NSCLC. Conclusions: We found that circPTN serves as a competing endogenous ribonucleic acid that promotes angiogenesis via the miR-595/LYRM5 signaling pathway in NSCLC. Targeting circPTN might be a promising new therapeutic strategy for NSCLC.
RESUMO
The efficacy of ginsenoside Rh2 (Rh2) in cancer therapy has been reported; however, its function in lung cancer remains unknown. To analyze the role of Rh2 in the inhibition of lung cancer cell proliferation in the present study, protein expression levels of E-cadherin, vimentin, ß-catenin, Smo, Gli1, and α-catenin were assessed by western blotting, whilst mRNA expression levels of TCF7 FZD8, Smo, Gli1, Gli2, and Gli3 were determined by reverse transcription-quantitative PCR in the A549 cell line. Phosphorylation sites were detected by proteomic methods and cell proliferation was analyzed by MTT assay. The present study revealed that Rh2 treatment significantly inhibited cell proliferation. Western blotting indicated that the expression levels of E-cadherin were increased and vimentin was downregulated in Rh2-treated cells compared with control cells. Treatment of A549 cells with Rh2 suppressed phosphorylation of five distinct proteins and increased phosphorylation of nine proteins. Among them, the phosphorylation of α-catenin at S641 was significantly induced. Rh2 treatment suppressed the expression levels of key genes involved in Wnt (Wnt3, transcription factor 7 and frizzled class receptor 8) and hedgehog [smoothened, frizzled class receptor (Smo), GLI family zinc finger (Gli)1, Gli2, and Gli3] signaling. Immunoblotting results indicated that ß-catenin, Smo and Gli1 protein expression levels were also suppressed by treatment with Rh2 compared with control treatment. Expression of α-catenin S641D, a phosphomimetic form of α-catenin, inhibited the accumulation of ß-catenin and Gli1 and inhibited cell proliferation and invasion. Furthermore, knockdown of ß-catenin (CTNNB1) or Gli1 with specific small interfering RNAs inhibited cell proliferation, whereas overexpression of these genes had an opposite effect. Additionally, overexpression of ß-catenin or Gli1 activated cell proliferation, even in the presence of Rh2, suggesting that Rh2 affects A549 cell proliferation through inhibition of Wnt and hedgehog signaling by phosphorylation of α-catenin at S641. Together, these data suggested that Rh2 treatment may inhibit the proliferation of A549 lung cancer cells. Further exploration of the underlying mechanism by which Rh2 inhibits cell proliferation is warranted.