C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1
Abstract Background Small nucleolar RNAs (snoRNAs) are dysregulated in many cancers, although their exact role in tumor genesis and progression remains unclear. Methods The expression profiles of snoRNAs in endometrial cancer (EC) tissues were analyzed using data from The Cancer Genome Atlas, and SN...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03802-z |
| _version_ | 1797977261503152128 |
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| author | Bingfeng Lu Xi Chen Xin Liu Jingwen Chen Honglei Qin Shuo Chen Yang Zhao |
| author_facet | Bingfeng Lu Xi Chen Xin Liu Jingwen Chen Honglei Qin Shuo Chen Yang Zhao |
| author_sort | Bingfeng Lu |
| collection | DOAJ |
| description | Abstract Background Small nucleolar RNAs (snoRNAs) are dysregulated in many cancers, although their exact role in tumor genesis and progression remains unclear. Methods The expression profiles of snoRNAs in endometrial cancer (EC) tissues were analyzed using data from The Cancer Genome Atlas, and SNORD104 was identified as an upregulated snoRNA in EC. The tumorigenic role of SNORD104 in EC was established in CCK8, colony formation, EdU, apoptosis, Transwell, and in vivo xenograft experiments. The molecular mechanisms of SNORD104 were analyzed by RNA immunoprecipitation (RIP), Nm-seq, RTL-P assay, RNA stability assay, qRT-PCR, and western blotting. Results Antisense oligonucleotide (ASO)-mediated knockdown of SNORD104 in Ishikawa cells significantly inhibited their proliferation, colony formation ability, migration, and invasion in vitro and increased apoptosis. On the other hand, overexpression of SNORD104 promoted EC growth in vivo and in vitro. RIP assay showed that SNORD104 binds to the 2ʹ-O-methyltransferase fibrillarin (FBL), and according to the results of Nm-seq and RTL-P assay, SNORD104 upregulated PARP1 (encoding poly (ADP-ribose) polymerase 1) 2ʹ-O-methylation. The binding of FBL to PARP1 mRNA was also verified by RIP assay. Furthermore, SNORD104 expression was positively correlated with PARP1 expression in EC tissues. In the presence of actinomycin D, SNORD104 increased the stability of PARP1 mRNA and promoted its nuclear localization. Finally, silencing FBL or PARP1 in the HEC1B cells overexpressing SNORD104 inhibited their proliferative and clonal capacities and increased apoptosis rates. Conclusions SNORD104 enhances PARP1 mRNA stability and translation in the EC cells by upregulating 2ʹ-O-methylation and promotes tumor growth. |
| first_indexed | 2024-04-11T05:04:10Z |
| format | Article |
| id | doaj.art-65c90b16e0704c1e9511d31b91e9db46 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T05:04:10Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-65c90b16e0704c1e9511d31b91e9db462022-12-25T12:27:29ZengBMCJournal of Translational Medicine1479-58762022-12-0120111410.1186/s12967-022-03802-zC/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1Bingfeng Lu0Xi Chen1Xin Liu2Jingwen Chen3Honglei Qin4Shuo Chen5Yang Zhao6Department of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Obstetrics and Gynecology, Department of Gynecologic Oncology Research Office, Guangdong Provincial Key Laboratory for Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityAbstract Background Small nucleolar RNAs (snoRNAs) are dysregulated in many cancers, although their exact role in tumor genesis and progression remains unclear. Methods The expression profiles of snoRNAs in endometrial cancer (EC) tissues were analyzed using data from The Cancer Genome Atlas, and SNORD104 was identified as an upregulated snoRNA in EC. The tumorigenic role of SNORD104 in EC was established in CCK8, colony formation, EdU, apoptosis, Transwell, and in vivo xenograft experiments. The molecular mechanisms of SNORD104 were analyzed by RNA immunoprecipitation (RIP), Nm-seq, RTL-P assay, RNA stability assay, qRT-PCR, and western blotting. Results Antisense oligonucleotide (ASO)-mediated knockdown of SNORD104 in Ishikawa cells significantly inhibited their proliferation, colony formation ability, migration, and invasion in vitro and increased apoptosis. On the other hand, overexpression of SNORD104 promoted EC growth in vivo and in vitro. RIP assay showed that SNORD104 binds to the 2ʹ-O-methyltransferase fibrillarin (FBL), and according to the results of Nm-seq and RTL-P assay, SNORD104 upregulated PARP1 (encoding poly (ADP-ribose) polymerase 1) 2ʹ-O-methylation. The binding of FBL to PARP1 mRNA was also verified by RIP assay. Furthermore, SNORD104 expression was positively correlated with PARP1 expression in EC tissues. In the presence of actinomycin D, SNORD104 increased the stability of PARP1 mRNA and promoted its nuclear localization. Finally, silencing FBL or PARP1 in the HEC1B cells overexpressing SNORD104 inhibited their proliferative and clonal capacities and increased apoptosis rates. Conclusions SNORD104 enhances PARP1 mRNA stability and translation in the EC cells by upregulating 2ʹ-O-methylation and promotes tumor growth.https://doi.org/10.1186/s12967-022-03802-zSNORD1042ʹ-O-methylationFibrillarinPARP1Endometrial cancer |
| spellingShingle | Bingfeng Lu Xi Chen Xin Liu Jingwen Chen Honglei Qin Shuo Chen Yang Zhao C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1 Journal of Translational Medicine SNORD104 2ʹ-O-methylation Fibrillarin PARP1 Endometrial cancer |
| title | C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1 |
| title_full | C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1 |
| title_fullStr | C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1 |
| title_full_unstemmed | C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1 |
| title_short | C/D box small nucleolar RNA SNORD104 promotes endometrial cancer by regulating the 2ʹ-O-methylation of PARP1 |
| title_sort | c d box small nucleolar rna snord104 promotes endometrial cancer by regulating the 2 o methylation of parp1 |
| topic | SNORD104 2ʹ-O-methylation Fibrillarin PARP1 Endometrial cancer |
| url | https://doi.org/10.1186/s12967-022-03802-z |
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