Crosstalk between Meg3 and miR-1297 regulates growth of testicular germ cell tumor through PTEN/PI3K/AKT pathway

Am J Transl Res. 2016 Feb 15;8(2):1091-9. eCollection 2016.


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.

Keywords: Maternally Expressed Gene 3 (Meg3); PTEN/PI3K/AKT; Testicular germ cell tumor (TGCT); miR-1297.