Propofol attenuates prostate cancer progression by upregulating TRHDE-AS1 expression, and METTL14 could mediate its m6A modification.

Propofol has become a microtubule-stabilizing drug for prostate cancer (PC) therapy, but propofol resistance impairs the therapeutic effect. This study aimed to explore the regulatory mechanism of propofol in the pathogenesis of PC through mechanisms involving N6-methyladenosine (m6A) modification. The changes in PC cell malignancy were evaluated by means of transwell, cell counting kit 8 (CCK-8), western blotting and tumour xenograft model assays. Long noncoding RNA TRHDE-AS1 and m6A methyltransferase METTL14 expression levels were determined via reverse transcription quantitative polymerase chain reaction (RT-qPCR). The m6A modification of TRHDE-AS1 which was mediated by METTL14 was confirmed by conducting methylated RNA immunoprecipitation (MeRIP) assay. We observed that propofol (200 μM) inhibited PC cell malignancy in vivo and in vitro, elucidating that it impaired cell proliferation, migration and tumour growth but induced apoptosis. TRHDE-AS1 expression was observed to be lower in PC cells and tissues, and propofol induced TRHDE-AS1 upregulation in PC cells. Propofol was capable of reversing the tumour-promoting effect of TRHDE-AS1 knockdown in PC cells. Additionally, METTL14 was upstream of TRHDE-AS1 to induce m6A modification of TRHDE-AS1 in PC cells. Collectively, our results show that propofol prevents PC progression by upregulating TRHDE-AS1 expression and METTL14 is involved in the m6A modification of TRHDE-AS1. These findings suggest that TRHDE-AS1 may be a potential therapeutic target for the improvement of propofol's therapeutic effect.

Chen Z ，Li Q ，Li Z ，Hu G ... -  《-》

METTL14-mediated N6-methyladenosine modification of SOX4 mRNA inhibits tumor metastasis in colorectal cancer.

Chen X ，Xu M ，Xu X ，Zeng K ，Liu X ，Pan B ，Li C ，Sun L ，Qin J ，Xu T ，He B ，Pan Y ，Sun H ，Wang S ... -  《Molecular Cancer》

METTL14-Mediated m6A Modification of TUG1 Represses Ferroptosis in Alzheimer's Disease via Inhibiting GDF15 Ubiquitination.

Alzheimer's disease (AD) is a neurodegenerative disease that remains a serious global health issue. Ferroptosis has been recognized as a vital driver of pathological progression of AD. However, the detailed regulatory mechanisms of ferroptosis during AD progression remain unclear. This study aimed to explore the regulatory role and mechanism of methyltransferase like 14 (METTL14) in ferroptosis in AD models. Serum samples were collected from 18 AD patients and 18 healthy volunteers to evaluate clinical correlation. Scopolamine-treated mice and Aβ1-42-stimulated SH-SY5Y cells were served as the in vivo and in vitro models of AD. Ferroptosis was detected by reactive oxygen species (ROS), Fe2+, total iron levels, and ferroptosis-related proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. The N6-methyladenosine (m6A) modification was detected by RNA methylation quantification kit and methylated RNA immunoprecipitation sequencing-quantitative real-time polymerase chain reaction (MeRIP-qPCR). Molecular mechanisms were investigated by RNA pull-down, RNA immunoprecipitation (RIP), and co-immunoprecipitation (Co-IP) assays. Cognitive disorder of AD mice was measured by Morris water maze test. METTL14 was down-regulated, while lncRNA taurine upregulated gene 1 (TUG1) was up-regulated in clinical patients and experimental models of AD. Functional experiments demonstrated that METTL14 overexpression or TUG1 silencing effectively attenuated Aβ1-42-induced ferroptosis and neurotoxicity in SH-SY5Y cells. Mechanistically, METTL14-mediated m6A modification reduced the stability of TUG1. Moreover, TUG1 promoted the ubiquitination and degradation of growth differentiation factor 15 (GDF15) by directly interacted with Smad ubiquitin regulatory factor 1 (SMURF1), which consequently inactivated nuclear factor erythroid 2-related factor 2 (NRF2). Rescue experiments indicated that GDF15 depletion reversed sh-TUG1-mediated protection against ferroptosis and neurotoxicity. Finally, Mettl14 overexpression repressed ferroptosis to ameliorate the cognitive disorder via modulating Tug1/Gdf15/Nrf2 pathway in vivo. METTL14 inhibited ferroptosis to ameliorate AD pathological development by m6A modification of TUG1 to activate GDF15/NRF2 axis, providing a novel therapeutic target for AD.

Gu X ，Song Y ，Liu X ，Cheng Z ，Min J ，Zhang Y ... -  《-》

METTL14-mediated lncRNA-FAS-AS1 promotes osteoarthritis progression by up-regulating ADAM8.

Zhang Z ，Mao H ，Li F ，Wang D ，Liu Y ... -  《-》

[Study on the Role and Mechanism of METTL3 Mediating the Up-regulation of 
m6A Modified Long Non-coding RNA THAP7-AS1 in Promoting the Occurrence of 
Lung Cancer].

Zhang Y ，Wang Y ，Liu M 《-》