SNORD60 promotes the tumorigenesis and progression of endometrial cancer through binding PIK3CA and regulating PI3K/AKT/mTOR signaling pathway.

Autor: Wu W; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Chen X; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Liu X; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Bao HJ; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Li QH; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Xian JY; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Lu BF; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Zhao Y; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China., Chen S; Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2023 Apr; Vol. 62 (4), pp. 413-426. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1002/mc.23495
Abstrakt: Endometrial carcinoma is a common gynecological malignant tumor, small nucleolar RNAs (snoRNAs) are involved in cancer development. However, researches on the roles of snoRNAs in endometrial carcinoma are limited. The expression levels of snoRNAs in endometrial cancer tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Antisense oligonucleotides (ASOs) and plasmids were used for transfection. Moreover, CCK-8, EdU, wound-healing assay, transwell, cell apoptosis, western blotting, and xenograft model were employed to examine the biological functions of related molecules. real-time reverse transcription polymerase chain reaction and western blotting were performed to detect messenger RNA (mRNA) and protein levels. Including bioinformatics, fluorescence in situ hybridization, RNA pulldown, actinomycin D and RTL-P assays were also carried out to explore the molecular mechanism. Analysis of data from TCGA showed that the expression level of small nucleolar RNA, C/D box 60 (SNORD60) in endometrial cancer tissues is observably higher than that in normal endometrial tissues. Further research suggested that SNORD60 played a carcinogenic role both in vitro and in vivo, and significantly upregulated the expression of PIK3CA. However, the carcinogenic effects can be reversed by knocking down fibrillarin (FBL) or PIK3CA. SNORD60 forms complexes by binding with 2'-O-methyltransferase fibrillarin, thus catalyzes the 2'-O-methylation (Nm) modification of PIK3CA mRNA and modulates the PI3K/AKT/mTOR signaling pathway, so as to promote the development of endometrial cancer. In short, SNORD60 might become a new biomarker for the therapy of endometrial cancer in the future and provide new strategies for diagnosis and treatment.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: