title: A dual PI3K/AKT/mTOR signaling inhibitor miR-99a suppresses endometrial carcinoma.
abstract: Activation of the PI3K/AKT/mTOR signaling pathway, a common mechanism in all subtypes of endometrial cancers (EC), plays an important role in the initiation and progression of many cancers. Inhibitors against various components of this pathway might promise a novel effective approach for targeted therapy for EC in the future. Intriguingly, two major members of this pathway, AKT1 and mTOR, were both reported to be the putative target genes of miR-99a, which were widely reported to function as a tumor suppressor in a variety of cancers. However, the direct role of miR-99a in endometrial cancer progression and the signaling pathways might been involved have never been deciphered. In this paper, we demonstrate that the expression of miR-99a was significantly suppressed in the EC tissues and was negatively correlated with the differentiation of tumors. Furthermore, we find that overexpression of miR-99a in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, suppression of cell invasion, and inhibition of tumor growth in vivo, which was mediated, at least partially, through dual-suppression of PI3K/AKT/mTOR pathway. This finding not only helps us understand the molecular mechanism of endometrial carcinogenesis, but also gives us a strong rationale to further investigate miR-99a as a potential biomarker and therapeutic target for EC.
authors.affiliation: Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Zhongzu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Tangshu
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Gynecology and Obstetrics, The Yongchuan Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Department of Gynecology and Obstetrics, The First Affiliated Hospital of Chongqing Medical University Chongqing 402160, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
keywords: PI3K/AKT/mTOR signaling pathway; endometrial carcinoma; miR-99a; microRNA