title: Crosstalk between Meg3 and miR-1297 regulates growth of testicular germ cell tumor through PTEN/PI3K/AKT pathway.
abstract: Maternally Expressed Gene 3 (Meg3) encodes a long non-coding RNA that has been recently shown to regulate tumorigenesis through its interaction with microRNA (miR). We have recently reported that miR-1297 might play a role in the regulation of PTEN/PI3k/Akt signaling pathway in testicular germ cell tumor (TGCT). However, a crosstalk between Meg3 and miR-1297 in TGCT has not been appreciated. Here, we analyzed the levels of Meg3, miR-1297 and PTEN in TGCT specimens, compared to paired adjacent non-tumor tissue (NT), and found that Meg3 levels were significantly decreased and miR-1297 levels were unchanged in TGCT. PTEN protein but not mRNA levels significantly decreased in TGCT. Bioinformatics analyses showed that miR-1297 bound to 3'-UTR of PTEN mRNA, while miR-1297 also bound to Meg3. Luciferase report assay showed that Meg3 overexpression abolished the effects of miR-1297 on 3'-UTR of PTEN mRNA, possibly through competitive binding, which was supported by double fluorescent in situ hybridization showing co-localization of intracellular Meg3 and miR-1297 signals in TGCT cells. Moreover, Meg3 overexpression abolished the inhibitory effects of miR-1297 on PTEN, resulting in deactivation of Akt and decreases in cell growth. Together, these data demonstrate a previous unappreciated pathway in which Crosstalk between Meg3 and miR-1297 regulates growth of TFCT through PTEN/PI3K/AKT signaling. Re-expression of Meg3 may be an attractive strategy for TGCT therapy.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Nian-Qin
authors.initials: NQ
authors.lastname: Yang
authors.affiliation: Department of Urology, The People's Hospital of Yichun City Jiangxi 336028, China.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: Luo
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Guo-Min
authors.initials: GM
authors.lastname: Wang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai 200032, China.
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Guo
keywords: Maternally Expressed Gene 3 (Meg3); PTEN/PI3K/AKT; Testicular germ cell tumor (TGCT); miR-1297