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Effects Of MiR-19b Inhibitor On STAT3 Signaling Pathway And Its Maligant Biological Behavior On Nasopharyngeal Carcinoma Cells

Posted on:2019-07-25Degree:MasterType:Thesis
Country:ChinaCandidate:L H BianFull Text:PDF
GTID:2404330545972835Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Nasopharyngeal carcinoma(NPC)is a nasopharyngeal epithelial malignacy with regional characteristics of southern China.Early diagnosis of NPC is very difficult,and prone to metastasize.About 70% of patients have metastasized when diagnosed with NPC.Metastasis and invasion is the main reason for treatment failure of NPC.Therefore,elucidating the molecular mechanism of distant metastasis in NPC will open a new chapter for the diagnosis and treatment of NPC.Signal transducer and activator of transcription 3(STAT3)signaling pathway is a key molecular pathway in the development and progression of NPC.Constituous activation of STAT3 signaling pathway promotes the proliferation and survival of NPC cells.Activated STAT3 forms homodimers,then translocates into the nucleus and functions as a tumor-promoting transcription factor.Activated STAT3 transmits the signals of cell proliferation and invasion and initiates the downstream effector genes,including Cyclin D1,B-cell-lymphoma-2(Bcl-2),Myeloid cell leukemia-1(Mcl-1)and so on,which can promote cell proliferation,survival and inhibit tumor cell apoptosis.Meanwhile,SOCS1 is an endogenous inhibitor of STAT3,inhibits the activity of JAK kinase and further inhibits the activation of STAT3 signaling pathway.miRNAs are important elements that regulated gene expression and can inhibit the expression of target genes through post-transcriptional regulation.Some studies have found that the expression of miR-19 b increases in NPC cells and tissues.SOCS1 is one of the target genes of miR-19 b.Therefore,we speculated that miR-19 b inhibitor may relieve miR-19b's targeted inhibition of SOCS1,then inhibits the activation of STAT3 signaling pathway,eventually inhibits the proliferation,migration and promots apoptosis of NPC cells.Objective: To illustrate mi R-19 b inhibitor relieve the inhibitory effects of SOCS1 by miR-19 b,thereby inhibiting STAT3 activation,further inhibiting the malignant biological behavior of NPC cells.Methods: 1.CCK-8 detected the effects of miR-19 b inhibitor on the proliferation of NPC cells C666-1;2.Flow cytometry deteced the effects of miR-19 b inhibitor on the apoptosis of NPC cells C666-1;3.Tanswell detected the effects of miR-19 b inhibitor on the migration of NPC cells C666-1;4.Western blot detected the effects of miR-19 b inhibitor on the expression of STAT3 signaling pathway associated proteins in NPC cells C666-1.Results: 1.mi R-19 b inhibitor could inhibit the proliferation of NPC cells C666-1.2.mi R-19 b inhibitor could promote the apoptosis of NPC cells C666-1.3.mi R-19 b inhibitor could inhibit the migration of NPC cells C666-1.4.mi R-19 b inhibitor up-regulated the expression of SOCS1,inhibited the phosphorylation of STAT3.Meanwhile,the downstream effector genes of STAT3 signaling pathway,including Cyclin D1,Mcl-1 and Bcl-2,were also decreased.Conclusions: miR-19 b inhibitor may target the STAT3 signaling pathway to suppress the malignant biological behavior of NPC cells and provide a novel therapeutic strategy for NPC.
Keywords/Search Tags:Nasopharyngeal carcinoma, miR-19b inhibitors, STAT3, Proliferation, Apoptosis
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