RESUMO
BACKGROUND: Mounting evidence supports that long noncoding RNAs (lncRNAs) have critical roles during cancer initiation and progression. In this study, we report that the plasmacytoma variant translocation 1 (PVT1) lncRNA is involved in breast cancer progression. METHODS: qRT-PCR and western blot were performed to detect the gene and protein expression. Colony formation would healing and transwell assays were used to detect cell function. Dual-luciferase reporter assay and RNA pull-down experiments were used to examine the mechanisms interaction between molecules. Orthotopic mouse models were established to evaluate the influence of PVT1 on tumor growth and metastasis in vivo. RESULTS: PVT1 is significant upregulated in breast cancer patients' plasma and cell lines. PVT1 promotes breast cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, PVT1 upregulates FOXQ1 via miR-128-3p and promotes epithelial-mesenchymal transition. In addition, PVT1 binds to the UPF1 protein, thereby inducing epithelial-mesenchymal transition, proliferation and metastasis in breast cancer cells. CONCLUSION: PVT1 may act as an oncogene in breast cancer through binding miR-128-3p and UPF1 and represents a potential target for BC therapeutic development.
Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante/genética , Animais , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Fatores de Transcrição Forkhead/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , RNA Helicases/genética , RNA Longo não Codificante/metabolismo , Transativadores/genética , Transativadores/metabolismoRESUMO
BACKGROUND: Expression patterns of microRNAs in serum are involved in potentially non-invasive biomarkers for various diseases. The purpose of this study is to examine the expression of miR-21 in serum of patients with diffuse large B-cell lymphoma (DLBCL) and to validate the significance of miR-21 in early diagnosis, genotyping, treatment options as well as its prognosis estimates of Chinese DLBCL. METHODS: miR-21 expression was detected by fluorescent quantity polymerase chain reaction (qPCR) in 9 DLBCL cell lines (OCI-Ly1, OCI-Ly3, OCI-Ly4, OCI-Ly7, OCI-Ly8, OCI-Ly10, OCI-Ly18, OCI-Ly19, and HBL), as well as in tumor tissue and serum samples from patients with DLBCL (germinal center B-cell-like (GCB) DLBCL 32; activated B-cell-like (ABC) DLBCL 30) and 50 healthy subjects. RESULTS: Expression of miR-21 was increased in DLBCL cell lines. Compared with the miR-21 expression of GCB subgroup (OCI-Ly1, OCI-Ly4, OCI-Ly7, OCI-Ly8, OCI-Ly18, OCI-Ly19), ABC subgroup (OCI-Ly3, OCI-Ly10, and HBL) has higher expression (t = 11.18, P < 0.01). Circulating miR-21 level in sera from patients with DLBCLwas associated with matched tumor tissue (r(2) = 0.931, P < 0.0001). Consistent with the in vitro, miR-21 expression levels in serum of patients with DLBCL [21.38(10.26-45.21)] were higher than those in serum of control cases [1.87(1.05-3.97); U = 168, P = 0.000]. Moreover, miR-21 expression levels in serum of patients with subgroup ABC [28.68(14.92~98.44)] were higher than that of patients with subgroup GCB [18.3(7.32~33.46); U = 336, P = 0.043]. miR-21 expression in serum of DLBCL with stage I and II were higher than those in stage III and IV (U = 62, P = 0.013 in GCB type; U = 53, P = 0.014 in ABC type). Compared with relapse-free survival in patients with DLBCL, high expression of miR-21 was associated with well prognosis (U = 259, P = 0.035). CONCLUSION: miR-21 expressed in the serum of patients with DLBCL from Chinese was associated with clinical stage, molecular subgroup, and prognosis estimates. miR-21 may be served as a biomarker in early diagnosis, genotyping, treatment options, and prognosis estimating of Chinese DLBCL.
Assuntos
Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/sangue , MicroRNAs/sangue , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Linfócitos B/metabolismo , Linfócitos B/patologia , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Feminino , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/etnologia , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Carga TumoralRESUMO
Various studies have reported that Huaier possesses anti-tumor effects. However, the mechanisms are not completely elucidated. Here, we found 66 differentially expressed miRNAs in Huaier-treated pulmonary adenocarcinoma A549 cells, with upregulation of miR-26b-5p. Transfection of A549 cells with miR-26b-5p mimic inhibited proliferation and induced apoptosis, while transfection of Huaier-treated A549 cells with a miR-26b-5p inhibitor reversed the effects of Huaier. EZH2 was verified as the target of miR-26b-5p. Thus, our findings indicate that Huaier might suppress proliferation and induce apoptosis in lung cancer cells via a miR-26b-5p-EZH2-mediated approach, which provides a new perspective for understanding the anti-tumor effects of Huaier.