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The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.

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Title: The small nucleolar RNA SNORA51 enhances breast cancer stem cell-like properties via the RPL3/NPM1/c-MYC pathway.
Authors: Li S; Department of Breast Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Jin Z; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Song X; Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China., Ma J; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Peng Z; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Yu H; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Song J; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Zhang Y; Department of Breast Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China., Sun X; Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China., He M; Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China., Yu X; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Jin F; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China., Zheng A; Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Source: Molecular carcinogenesis [Mol Carcinog] 2024 Jun; Vol. 63 (6), pp. 1117-1132. Date of Electronic Publication: 2024 Feb 29.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8811105 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-2744 (Electronic) Linking ISSN: 08991987 NLM ISO Abbreviation: Mol Carcinog Subsets: MEDLINE
Imprint Name(s): Publication: <2005- > : [Hoboken, N.J.] : Wiley-Liss
Original Publication: New York : Alan R. Liss, Inc., c1988-
MeSH Terms: Breast Neoplasms*/pathology , Breast Neoplasms*/genetics , Breast Neoplasms*/metabolism , Neoplastic Stem Cells*/metabolism , Neoplastic Stem Cells*/pathology , Proto-Oncogene Proteins c-myc*/metabolism , Proto-Oncogene Proteins c-myc*/genetics , RNA, Small Nucleolar*/genetics , RNA, Small Nucleolar*/metabolism , Ribosomal Protein L3*/genetics , Ribosomal Protein L3*/metabolism , Cell Proliferation* , Nucleophosmin*, Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Animals ; Female ; Humans ; Mice ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Prognosis ; Signal Transduction
Abstract: Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.
(© 2024 Wiley Periodicals LLC.)
References: Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209‐249. doi:10.3322/caac.21660.
Al‐Hajj M, Wicha MS, Benito‐Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci. 2003;100(7):3983‐3988. doi:10.1073/pnas.0530291100.
Pece S, Tosoni D, Confalonieri S, et al. Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell. 2010;140(1):62‐73. doi:10.1016/j.cell.2009.12.007.
Arima Y, Hayashi N, Hayashi H, et al. Loss of p16 expression is associated with the stem cell characteristics of surface markers and therapeutic resistance in estrogen receptor‐negative breast cancer. Int J Cancer. 2012;130(11):2568‐2579. doi:10.1002/ijc.26271.
Bai X, Ni J, Beretov J, Graham P, Li Y. Cancer stem cell in breast cancer therapeutic resistance. Cancer Treat Rev. 2018;69:152‐163. doi:10.1016/j.ctrv.2018.07.004.
Butti R, Gunasekaran VP, Kumar TVS, Banerjee P, Kundu GC. Breast cancer stem cells: biology and therapeutic implications. Int J Biochem Cell Biol. 2019;107:38‐52. doi:10.1016/j.biocel.2018.12.001.
Quaglino E, Conti L, Cavallo F. Breast cancer stem cell antigens as targets for immunotherapy. Sem Immunol. 2020;47:101386. doi:10.1016/j.smim.2020.101386.
Filipowicz W, Pelczar P, Pogacic V, Dragon F. Structure and biogenesis of small nucleolar RNAs acting as guides for ribosomal RNA modification. Acta Biochim Pol. 1999;46(2):377‐389.
Maxwell E, Fournier M. The small nucleolar RNAs. Annu Rev Biochem. 1995;64:897‐934. doi:10.1146/annurev.bi.64.070195.004341.
Watkins NJ, Bohnsack MT. The box C/D and H/ACA snoRNPs: key players in the modification, processing and the dynamic folding of ribosomal RNA. WIREs RNA. 2012;3(3):397‐414. doi:10.1002/wrna.117.
Henras AK, Plisson‐Chastang C, Humbert O, Romeo Y, Henry Y. Synthesis, function, and heterogeneity of snoRNA‐guided posttranscriptional nucleoside modifications in eukaryotic ribosomal RNAs. Enzymes. 2017;41:169‐213. doi:10.1016/bs.enz.2017.03.007.
Gong J, Li Y, Liu C, et al. A pancancer analysis of the expression and clinical relevance of small nucleolar RNAs in human cancer. Cell Rep. 2017;21(7):1968‐1981. doi:10.1016/j.celrep.2017.10.070.
Romano G, Veneziano D, Acunzo M, Croce CM. Small noncoding RNA and cancer. Carcinogenesis. 2017;38(5):485‐491. doi:10.1093/carcin/bgx026.
Zhu W, Niu J, He M, et al. SNORD89 promotes stemness phenotype of ovarian cancer cells by regulating Notch1‐c‐Myc pathway. J Transl Med. 2019;17(1):259. doi:10.1186/s12967-019-2005-1.
Zhang L, Ma R, Gao M, et al. SNORA72 activates the Notch1/c‐Myc pathway to promote stemness transformation of ovarian cancer cells. Front Cell Dev Biol. 2020;8:583087. doi:10.3389/fcell.2020.583087.
Zou AE, Ku J, Honda TK, et al. Transcriptome sequencing uncovers novel long noncoding and small nucleolar RNAs dysregulated in head and neck squamous cell carcinoma. RNA. 2015;21(6):1122‐1134. doi:10.1261/rna.049262.114.
Wang H, Ma P, Liu P, Chen B, Liu Z. Small nucleolar RNA U2_19 promotes hepatocellular carcinoma progression by regulating Wnt/β‐catenin signaling. Biochem Biophys Res Commun. 2018;500(2):351‐356. doi:10.1016/j.bbrc.2018.04.074.
Zheng D, Zhang J, Ni J, et al. Small nucleolar RNA 78 promotes the tumorigenesis in non‐small cell lung cancer. J Exp Clin Cancer Res. 2015;34:49. doi:10.1186/s13046-015-0170-5.
Mannoor K, Shen J, Liao J, Liu Z, Jiang F. Small nucleolar RNA signatures of lung tumor‐initiating cells. Mol Cancer. 2014;13:104. doi:10.1186/1476-4598-13-104.
Hu T, Lu C, Xia Y, et al. Small nucleolar RNA SNORA71A promotes epithelial–mesenchymal transition by maintaining ROCK2 mRNA stability in breast cancer. Mol Oncol. 2022;16(9):1947‐1965. doi:10.1002/1878-0261.13186.
Russo G, Cuccurese M, Monti G, et al. Ribosomal protein L7a binds RNA through two distinct RNA‐binding domains. Biochem J. 2005;385(Pt 1):289‐299. doi:10.1042/BJ20040371.
Wang H, Zhao LN, Li KZ, Ling R, Li XJ, Wang L. Overexpression of ribosomal protein L15 is associated with cell proliferation in gastric cancer. BMC Cancer. 2006;6:91. doi:10.1186/1471-2407-6-91.
Chaudhuri S, Vyas K, Kapasi P, et al. Human ribosomal protein L13a is dispensable for canonical ribosome function but indispensable for efficient rRNA methylation. RNA. 2007;13(12):2224‐2237. doi:10.1261/rna.694007.
Catez F, Dalla Venezia N, Marcel V, Zorbas C, Lafontaine DLJ, Diaz JJ. Ribosome biogenesis: an emerging druggable pathway for cancer therapeutics. Biochem Pharmacol. 2019;159:74‐81. doi:10.1016/j.bcp.2018.11.014.
Turi Z, Lacey M, Mistrik M, Moudry P. Impaired ribosome biogenesis: mechanisms and relevance to cancer and aging. Aging. 2019;11(8):2512‐2540. doi:10.18632/aging.101922.
Nicolas E, Parisot P, Pinto‐Monteiro C, de Walque R, De Vleeschouwer C, Lafontaine DLJ. Involvement of human ribosomal proteins in nucleolar structure and p53‐dependent nucleolar stress. Nat Commun. 2016;7:11390. doi:10.1038/ncomms11390.
James A, Wang Y, Raje H, Rosby R, DiMario P. Nucleolar stress with and without p53. Nucleus. 2014;5(5):402‐426. doi:10.4161/nucl.32235.
Li S, Ma J, Zheng A, Song X, Chen S, Jin F. DEAD‐box helicase 27 enhances stem cell‐like properties with poor prognosis in breast cancer. J Transl Med. 2021;19(1):334. doi:10.1186/s12967-021-03011-0.
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45(W1):W98‐W102. doi:10.1093/nar/gkx247.
Zheng A, Zhang L, Song X, Wang Y, Wei M, Jin F. Clinical implications of a novel prognostic factor AIFM3 in breast cancer patients. BMC Cancer. 2019;19(1):451. doi:10.1186/s12885-019-5659-4.
Yan Y, Liu F, Han L, et al. HIF‐2α promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways. J Exp Clin Cancer Res. 2018;37(1):256. doi:10.1186/s13046-018-0925-x.
Russo A, Esposito D, Catillo M, Pietropaolo C, Crescenzi E, Russo G. Human rpL3 induces G₁/S arrest or apoptosis by modulating p21waf1/cip1levels in a p53‐independent manner. Cell Cycle. 2013;12(1):76‐87. doi:10.4161/cc.22963.
Scaloni F, Federici L, Brunori M, Gianni S. Deciphering the folding transition state structure and denatured state properties of nucleophosmin C‐terminal domain. Proc Natl Acad Sci. 2010;107(12):5447‐5452. doi:10.1073/pnas.0910516107.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663‐676. doi:10.1016/j.cell.2006.07.024.
Mamlouk S, Wielockx B. Hypoxia‐inducible factors as key regulators of tumor inflammation. Int J Cancer. 2013;132(12):2721‐2729. doi:10.1002/ijc.27901.
Ke Q, Costa M. Hypoxia‐inducible factor‐1 (HIF‐1. Mol Pharmacol. 2006;70(5):1469‐1480. doi:10.1124/mol.106.027029.
Philip B, Ito K, Moreno‐Sanchez R, Ralph SJ. HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression. Carcinogenesis. 2013;34(8):1699‐1707. doi:10.1093/carcin/bgt209.
Schwab LP, Peacock DL, Majumdar D, et al. Hypoxia‐inducible factor 1α promotes primary tumor growth and tumor‐initiating cell activity in breast cancer. Breast Cancer Res. 2012;14(1):R6. doi:10.1186/bcr3087.
Okugawa Y, Toiyama Y, Toden S, et al. Clinical significance of SNORA42 as an oncogene and a prognostic biomarker in colorectal cancer. Gut. 2017;66(1):107‐117. doi:10.1136/gutjnl-2015-309359.
Wu L, Chang L, Wang H, Ma W, Peng Q, Yuan Y. Clinical significance of C/D box small nucleolar RNA U76 as an oncogene and a prognostic biomarker in hepatocellular carcinoma. Clini Res Hepatol Gastroenterol. 2018;42(1):82‐91. doi:10.1016/j.clinre.2017.04.018.
Wu L, Zheng J, Chen P, Liu Q, Yuan Y. Small nucleolar RNA ACA11 promotes proliferation, migration and invasion in hepatocellular carcinoma by targeting the PI3K/AKT signaling pathway. Biomed Pharmacother. 2017;90:705‐712. doi:10.1016/j.biopha.2017.04.014.
Zhang C, Zhao L, Wu H, et al. C/D‐Box Snord105b promotes tumorigenesis in gastric cancer via ALDOA/C‐Myc pathway. Cell Physiol Biochem. 2018;45(6):2471‐2482. doi:10.1159/000488265.
Wang K, Song X, Li X, Zhang Z, Xie L, Song X. Plasma SNORD83A as a potential biomarker for early diagnosis of non‐small cell lung cancer. Future Oncol. 2022;18(7):821‐832. doi:10.2217/fon-2021-1278.
Menon SS, Guruvayoorappan C, Sakthivel KM, Rasmi RR. Ki‐67 protein as a tumour proliferation marker. Clin Chim Acta. 2019;491:39‐45. doi:10.1016/j.cca.2019.01.011.
Liu Z, Pang Y, Jia Y, et al. SNORA23 inhibits HCC tumorigenesis by impairing the 2′‐O‐ribose methylation level of 28S rRNA. Cancer Biol Med. 2021;19(1):104. doi:10.20892/j.issn.2095-3941.2020.0343.
Cao P, Yang A, Wang R, et al. Germline duplication of SNORA18L5 increases risk for HBV‐related hepatocellular carcinoma by altering localization of ribosomal proteins and decreasing levels of p53. Gastroenterology. 2018;155(2):542‐556. doi:10.1053/j.gastro.2018.04.020.
Dez C, Tollervey D. Ribosome synthesis meets the cell cycle. Curr Opin Microbiol. 2004;7(6):631‐637. doi:10.1016/j.mib.2004.10.007.
Esposito D, Crescenzi E, Sagar V, Loreni F, Russo A, Russo G. Human rpL3 plays a crucial role in cell response to nucleolar stress induced by 5‐FU and L‐OHP. Oncotarget. 2014;5(22):11737‐11751. doi:10.18632/oncotarget.2591.
Li Z, Boone D, Hann SR. Nucleophosmin interacts directly with c‐Myc and controls c‐Myc‐induced hyperproliferation and transformation. Proc Natl Acad Sci. 2008;105(48):18794‐18799. doi:10.1073/pnas.0806879105.
Grant Information: 2022-MS-192 Natural Science Foundation of Liaoning Province; CJBSRAF-2022 Chinese Breast Surgery Young Doctor Research Support Project; 82073282 National Natural Science Foundation of China; 82203873 National Natural Science Foundation of China
Contributed Indexing: Keywords: NPM1/c‐MYC pathway; breast cancer stem cell; prognosis; ribosomal protein L3; small nucleolar RNA 51
Substance Nomenclature: 0 (Nuclear Proteins)
117896-08-9 (Nucleophosmin)
0 (Proto-Oncogene Proteins c-myc)
0 (Ribosomal Proteins)
0 (RNA, Small Nucleolar)
0 (RPL3 protein, human)
0 (NPM1 protein, human)
0 (Ribosomal Protein L3)
Entry Date(s): Date Created: 20240229 Date Completed: 20240515 Latest Revision: 20240731
Update Code: 20260130
DOI: 10.1002/mc.23713
PMID: 38421204
Database: MEDLINE
Description
ISSN:1098-2744
DOI:10.1002/mc.23713