期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 105, 期 -, 页码 1106-1116出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.06.075
关键词
miR-149; Proliferation; Apoptosis; GIT1; PI3K/AKT/mTOR pathway; Cervical cancer
MiRNAs are emerging as critical regulators in carcinogenesis and tumor progression. Recently, miR-149 has been demonstrated as a tumor suppressor in several cancers, but its functions in the context of cervical cancer remains unknown. The objective of this study is to investigate the clinicopathological and prognostic values of miR-149 expression and its roles in cervical cancer progression. In this study, miR-149 expression is decreased in CC tissues and cell lines compare with paired normal tissues and normal epithelial cell, respectively. Moreover, the restoration of miR-149 expression inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro. We further proved that miR-149 overexpression suppresse the growth of cervical cancer cells in vivo using a mouse xenograft model. Dual luciferase assays identified the GIT1 as a novel direct target of miR-149. To identify the mechanisms, we investigated the PI3K/AKT/mTOR pathway and found that the expression of PI3K, AKT and mTOR were suppressed in cells which were transfected with miR-149 mimics. Taken together, these results indicate that miR-149 is involved in the carcinogenesis and development of cervical cancer by targeting GIT1 via PI3K/AKT/mTOR pathway. Given these, our data suggest that miR-149 functions as a tumor suppressor and may serve as a biomarker or useful therapeutic target of cervical cancer.
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