当前位置： SCI文献检索 > JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH期刊下所有文献 > LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling.

LncRNA XIST/miR-34a axis modulates the cell proliferation and tumor growth of thyroid cancer through MET-PI3K-AKT signaling.

Abstract：

BACKGROUND:Thyroid cancer is one of the most prevalent malignancies in endocrine system. Further understanding and revealing the molecular mechanism underlying thyroid cancer are indispensable for the development of effective diagnosis and treatments. In the present study, we attempted to provide novel basis for targeted therapy for thyroid cancer from the aspect of lncRNA-miRNA-mRNA interaction. METHODS:The expression and cellular function of XIST (X-inactive specific transcript) was determined. miRNAs which may be direct targets of XIST were screened for from online GEO database and miR-34a was selected. Next, the predicted binding between XIST and miR-34a, and the dynamic effect of XIST and miR-34a on downstream MET (hepatocyte growth factor receptor)-PI3K (phosphoinositide 3-kinase)-AKT (α-serine/threonine-protein kinase) signaling was evaluated. RESULTS:XIST was significantly up-regulated in thyroid cancer tissues and cell lines; XIST knockdown suppressed the cell proliferation in vivo and the tumor growth in vitro. Based on online database and online tool prediction results, miR-34a was underexpressed in thyroid cancer and might be a direct target of XIST. Herein, we confirmed the negative interaction between XIST and miR-34a; moreover, XIST knockdown could reduce the protein levels of MET, a downstream target of miR-34a, and the phosphorylation of PI3K and AKT. In thyroid cancer tissues, MET mRNA and protein levels of MET were up-regulated; MET was positively correlated with XIST while negatively correlated with miR-34a, further confirming that XIST serves as a ceRNA for miR-34a through sponging miR-34a, competing with MET for miR-34a binding, and finally modulating thyroid cancer cell proliferation and tumor growth. CONCLUSION:In the present study, we provided novel experimental basis for targeted therapy for thyroid cancer from the aspect of lncRNA-miRNA-mRNA interaction.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Liu H,Deng H,Zhao Y,Li C,Liang Y

doi

10.1186/s13046-018-0950-9

subject

Has Abstract

pub_date

2018-11-21 00:00:00

pages

279

issue

1

eissn

0392-9078

issn

1756-9966

pii

10.1186/s13046-018-0950-9

journal_volume

37

pub_type

杂志文章

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