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      Box C/D snoRNA SNORD89 influences the occurrence and development of endometrial cancer through 2’- O-methylation modification of Bim

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          Abstract

          The small nucleolar RNA (snoRNA) is a type of small non-coding RNA widely distributed in the nucleoli of eukaryotic cells, promoting cancer development. The aim of this study was to assess box C/D snoRNA 89 ( SNORD89) dysregulations in endometrial cancer. According to the TCGA database as well as the International Federation of Gynecology and Obstetrics (FIGO), higher SNORD89 expression is found in endometrial cancer tissues. In addition, the SNORD89 expression level was higher in endometrial carcinoma with lymph node metastasis than in endometrial carcinoma without lymph node metastasis. By interacting with the conservative chaperone protein methylase fibrillarin (Fbl), SNORD89 inhibits the translation process of the Bim gene, leading to a decrease in Bim protein. Cancer-promoting effect of SNORD89 can be reversed by Fbl knockdown or Bim overexpressing. What’s more, ASO-mediated silencing of SNORD89 could inhibit endometrial cancer cell proliferation and migration ability. Taken together, SNORD89 can modify Bim through 2′- O-methylation and affect downstream signaling pathways to promote endometrial cancer occurrence and development. The role of methylation modification in the prevention and treatment of endometrial cancer provides a new understanding and SNORD89 may be a new diagnostic and therapeutic target for endometrial cancer.

          Abstract

          Mechanism of action of SNORD89

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          Most cited references37

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          Non-coding RNA networks in cancer

          Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.
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            A human snoRNA with microRNA-like functions.

            Small noncoding RNAs function in concert with Argonaute (Ago) proteins to regulate gene expression at the level of transcription, mRNA stability, or translation. Ago proteins bind small RNAs and form the core of silencing complexes. Here, we report the analysis of small RNAs associated with human Ago1 and Ago2 revealed by immunoprecipitation and deep sequencing. Among the reads, we find small RNAs originating from the small nucleolar RNA (snoRNA) ACA45. Moreover, processing of ACA45 requires Dicer activity but is independent of Drosha/DGCR8. Using bioinformatic prediction algorithms and luciferase reporter assays, we uncover the mediator subunit CDC2L6 as one potential mRNA target of ACA45 small RNAs, suggesting a role for ACA45-processing products in posttranscriptional gene silencing. We further identify a number of human snoRNAs with microRNA (miRNA)-like processing signatures. We have, therefore, identified a class of small RNAs in human cells that originate from snoRNAs and can function like miRNAs.
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              The functional role of long non-coding RNA in human carcinomas

              Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these RNA species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in human cancer.
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                Author and article information

                Contributors
                chenshuo077003@163.com
                Journal
                Cell Death Discov
                Cell Death Discov
                Cell Death Discovery
                Nature Publishing Group UK (London )
                2058-7716
                5 July 2022
                5 July 2022
                2022
                : 8
                : 309
                Affiliations
                GRID grid.417009.b, ISNI 0000 0004 1758 4591, 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, 510150 China
                Author information
                http://orcid.org/0000-0003-3226-8127
                http://orcid.org/0000-0002-5122-3656
                Article
                1102
                10.1038/s41420-022-01102-5
                9256700
                35790714
                70e0ffd0-eb05-4373-9c81-09baa4f68336
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 April 2022
                : 24 June 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81872115
                Award ID: 82072854
                Award Recipient :
                Funded by: This work was supported by Guangzhou key medical discipline.
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                endometrial cancer,tumour biomarkers
                endometrial cancer, tumour biomarkers

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