SNORD104通过调控PIK3CA的2'-O-甲基化促进子宫内膜癌发生发展的作用及机制研究

doi:10.3969/j.issn.1006-6233.2025.02.001

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Abstract Objective: To investigate the role of C/D box small nucleolar RNA 104 (SNORD104) in occurrence and progress of endometrial cancer (EC) and its possible mechanisms. Methods: The expression of SNORD104 in human EC tissues and normal endometrial tissues were analyzed in TCGA database. From January 2021 to December 2022, the endometrial tissues were collected from 118 patients who were diagnosed with EC and underwent surgical curettage at the Second Affiliated Hospital of Soochow University and 31 patients with simple endometrial hyperplasia. In additionally, the normal endometrial epithelial cells (ESC) and EC cells (Ishikawa, RL95-2, KLE, and HEC-1B) were selected as target cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect SNORD104 expression in human EC cells and normal endometrial tissues. The fluorescence in situ hybridization (FISH) was used to detect SNORD104 subcellular localization. Ishikawa cells were randomly divided into OE (overexpression)-NC, OE-SNORD104, OE-SNORD104+si (small interfering RNA)-NC, OE-SNORD104+si-PIK3CA, and OE-SNORD104+si-FBL groups, and HEC-1B was randomly divided into antisense oligonucleotide (ASO)-NC group and ASO-SNORD104 group. qRT-PCR were performed to the detected the expression of SNORD104 and PIK3CA, EdU staining, scratch assays, Transwell assays and flow cytometry were employed to detect the cell proliferation, migration, invasion and apoptosis. RTL-P assay and actinomycin D assay were conducted to detect 2'-O-methylation level and RNA stability. RNA Immunoprecipitation (RIP) was applied to detect the binding relationship between FBL and SNORD104with PIK3CA, and Western blot was used to assess the proteins expression of PI3K/AKT/mTOR pathway. Results: The results of TCGA database and qRT-PCR showed that the expression level of SNORD104 was significantly increased in EC tissues and cells compared with those of normal human endometrial tissues and cells, which was correlated with FIGO stage and lymph node metastasis in EC patients. Compared with those of the OE-NC group, EdU-positive rate, migration index and number of invasive cells were significantly decreased, but apoptosis rate was significantly increased in the OE-SNORD104 group (P<0.05). Compared with those of the ASO-NC group, EdU-positive rate, cell migration index and number of invasive cells were significantly decreased, but cell apoptosis rate was significantly increased in ASO-SNORD104 group (P<0.05). BLAST sequence comparison showed the possible presence of SNORD104 binding sites in the mRNA of PIK3CA. Kaplan-Meier Plotter survival analysis showed that high expression of PIK3CA in EC was positively correlated with patient survival. In the result for RIP experiments, compared with IgG antibody-treated Ishikawa cells, FBL in both PIK3CA and SNORD104 enrichment were significantly elevated in antibody-treated cells (P<0.05). RTL-P experiments revealed when concentration of NTPs was low, PIK3CA expression was significantly reduced in the OE-SNORD104 group compared to the OE-NC group (P<0.05). The expression of PIK3CA mRNA and p110α, p-AKT and mTOR proteins were significantly decreased in the ASO-SNORD104 group than in ASO-NC group, but which were significantly elevated in the OE-SNORD104 group than in the OE-NC group. The mRNA expression of PIK3CA was significantly decreased in the OE-SNORD104+si-FBL group than in the si-NC group (P<0.05). Significantly reduced EdU-positive cell rate, cell migration index and invasive cell number, and increased apoptosis rate in the OE-SNORD104+si-NC group and OE-SNORD104+si-FBL group compared with the OE-SNORD104+si-NC group (P<0.05). Conclusion: SNORD104 promotes EC development by binding to 2'-O-methyltransferase fibrillar protein FBL to form a complex that catalyzes 2'-O-methylation modification of PIK3CA mRNA and activates the PI3K/AKT/mTOR signaling pathway.

Key words： Endometrial cancer SNORD104 2'-O-methylation PIK3CA PI3K/AKT/mTOR signaling pathway

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	HE Chunlei
	YANG Zhujuan
	ZHU Xinpeng
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HE Chunlei,YANG Zhujuan,ZHU Xinpeng, et al. Role and Mechanism of SNORD104 in the Occurrence and Progress of Endometrial Cancer by Regulating 2'-O-methylation of PIK3CA[J]. HeBei Med, 2025, 31(2): 177-185.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2025.02.001 OR http://www.hbyxzzs.cn/EN/Y2025/V31/I2/177

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