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

• Published in: Clinical and experimental pharmacology & physiology 2024-11, Vol.51 (11), p.e13924-n/a
• Main Authors: Chen, Zhuo, Li, Quanfu, Li, Zhong, Hu, Guangjun
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Adenosine - metabolism; Adenosine - pharmacology; Animals; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cholecystokinin; Disease Progression; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immunoprecipitation; Male; Malignancy; Methyltransferases - genetics; Methyltransferases - metabolism; METTL14; Mice; Mice, Nude; N6-methyladenosine; Pathogenesis; Pheochromocytoma cells; Polymerase chain reaction; Propofol; Propofol - pharmacology; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Regulatory mechanisms (biology); Reverse transcription; RNA modification; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Therapeutic targets; TRHDE‐AS1; Tumors; Up-Regulation - drug effects; Western blotting; Xenotransplantation
• ISSN: 0305-1870; 1440-1681; 1440-1681
• DOI: 10.1111/1440-1681.13924

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. Propofol prevents progression of prostate cancer via METTL14‐mediated m6A modification of long noncoding RNA TRHDE‐AS1.