In prior research, evidence has been found for a relation between low exposure of long non-coding RNAs (lncRNAs) and prostate tumor genesis. This study aims to clarify the underlying mechanisms of lncRNA GAS5 in prostate cancer (PCa). In total, 118 pairs of PCa tissues and matched adjacent non-tumor tissues were collected. Additionally, lncRNA GAS5 exposure levels were determined using RT-PCR and in situ hybridization. In addition, dual-luciferase report assay was performed to verify the target effect of lncRNA GAS5 on miR-103. The exposure levels of the proteins related to the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) axis, including AKT, mTOR, and S6K1, were measured by western blot PC3 cells infected with lncRNA GAS5 mimic; lncRNA GAS5 siRNA; or a combination of lncRNA and miR-103. The proliferation, invasion, and migration ability of PC3 cells after being infected were tested by MTT assay, wound healing assay, and transwell assays. Finally, nude mouse xenograft models were used to measure lncRNA GAS5 effects on prostate tumor growth in vivo. The lncRNA GAS5 levels were reduced significantly in the PCa tissues and cell lines (P < 0.05). A low exposure of lncRNA GAS5 caused AKT/mTOR signaling pathway activation in PC3 cells (P < 0.05). In addition, over-exposure of lncRNA GAS5 was proven to significantly decelerate PCa cell progression in vitro and tumor growth in vivo through inactivating the AKT/mTOR signaling pathway (P < 0.05). This study proves that lncRNA GAS5 plays a significant role in the decelerating PCa development via mediating the AKT/mTOR signaling pathway through targeting miR-103.
Prostate cancer LncRNA GAS5 miR-103 AKT/mTOR signaling pathway Proliferation Invasion Migration Xenograft model
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This work was supported by Changzhou Municipal Science and Technology Bureau Support Project (CE20135046) and Jiangsu Provincial Health Department General Research Project (H201348).
Compliance with ethical standards
The Animal Ethics Committee of Fudan University approved all protocols of animal experiments.
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