m6A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway.
Han ZhangPing ZhangChongde LongXinqi MaHao HuangXielan KuangHan DuHan TangXiangtian LingJie NingHuijun LiuXizhi DengYuxiu ZouRenchun WangHao ChengShuibin LinQingjiong ZhangJianhua YanHuangxuan ShenPublished in: Journal of cellular and molecular medicine (2020)
Retinoblastoma (RB) is a common intraocular malignancy in children. Due to the poor prognosis of RB, it is crucial to search for efficient diagnostic and therapeutic strategies. Studies have shown that methyltransferase-like 3 (METTL3), a major RNA N (6)-adenosine methyltransferase, is closely related to the initiation and development of cancers. Nevertheless, whether METTL3 is associated with RB remains unexplored. Therefore, we investigated the function and mechanisms of METTL3 in the regulation of RB progression. We manipulated METTL3 expression in RB cells. Then, cell proliferation, apoptosis, migration and invasion were analysed. We also analysed the expression of PI3K/AKT/mTOR pathway members. Finally, we incorporated subcutaneous xenograft mouse models into our studies. The results showed that METTL3 is highly expressed in RB patients and RB cells. We found that METTL3 knockdown decreases cell proliferation, migration and invasion of RB cells, while METTL3 overexpression promotes RB progression in vitro and in vivo. Moreover, two downstream members of the PI3K/AKT/mTOR pathway, P70S6K and 4EBP1, were affected by METTL3. Our study revealed that METTL3 promotes the progression of RB through PI3K/AKT/mTOR pathways in vitro and in vivo. Targeting the METTL3/PI3K/AKT/mTOR signalling axis could be a promising therapeutic strategy for the treatment of RB.
Keyphrases
- poor prognosis
- cell proliferation
- cell cycle arrest
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- pi k akt
- ejection fraction
- transcription factor
- mouse model
- mass spectrometry
- chronic kidney disease
- high resolution
- single cell
- patient reported
- case control
- atomic force microscopy
- high speed
- cataract surgery