AccScience Publishing / TD / Online First / DOI: 10.36922/td.3670
Submit to TD
Cite this article
40
Download
760
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Investigating long noncoding RNA HA117 and its possible regulatory network in osteosarcoma

Hongxia Chen1† ,  Zhiyong Cheng2† ,  Wei Wang3 ,  Zhenhua Zhuang4 ,  Xiaoping Huang3 ,  Ning Wang3*
Show Less
1 Department of Hematology, Chong Qing University Three Gorges Hospital, Chongqing, China
2 Orthopedic Trauma Unit, Chong Qing University Three Gorges Hospital, Chongqing, China
3 Department of Oncology, Chong Qing University Three Gorges Hospital, Chongqing, China
4 Chengdu Life Baseline Technology CO., LTD, Chengdu, Sichuan, China
Tumor Discovery 2024, 3(3), 3670 https://doi.org/10.36922/td.3670
Submitted: 15 May 2024 | Accepted: 3 July 2024 | Published: 7 August 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Osteosarcoma, a primary malignant bone tumor, is the third most common cancer in children and adolescents under 20 years old. In recent decades, many osteosarcomar elated molecular targets, including long noncoding RNA (lncRNA), have been discovered or confirmed. This study aims to elucidate the gene expression and possible regulatory mechanisms of lncRNA HA117 in osteosarcoma. To achieve this, we downloaded 51 whole-transcriptome osteosarcoma sequencing samples from the NCBI Sequence Read Archive database and performed bioinformatics analysis. Geneexpression analysis of HA117 revealed no significant difference between the tumor and adjacent tissues. However, HA117 exhibited significant down-regulation in bothfresh and formalin‐fixed paraffin-embedded (FFPE) samples after chemotherapy. Bycombining two target gene prediction methods, we identified 11 and 83 target genes for HA117 in fresh and FFPE samples, respectively. Functional analysis indicated that these target genes are mainly located in the cytoplasm and nucleus, with most related to protein binding. In addition, Reactome analysis demonstrated that these target genes participate in the regulation of multiple metabolic pathways, predominantly in cellular responses to stress. Our findings suggest that chemotherapy may regulate downstream target genes by altering the expression of HA117, thereby inducing cellular stress response. Overall, our results indicate that HA117 may not function as an oncogene but could serve as a therapeutic target in osteosarcoma.

Keywords
LncRNA
Osteosarcoma
Differentially expressed genes
Gene Ontology analysis
Reactome analysis
Target gene
Funding
This research was funded by the Natural Science Foundation of Chongqing, Project number cstc2020jcyjmsxmX0966.
Conflict of interest
The authors declare no competing interests.
References
  1. Bernardini G, Laschi M, Geminiani M, Santucci A. Proteomics of osteosarcoma. Expert Rev Proteomics. 2014;11(3):331-343. doi: 10.1586/14789450.2014.900445

 

  1. Chen R, Huang LH, Gao YY, Yang JZ, Wang Y. Identification of differentially expressed genes in MG63 osteosarcoma cells with drug‑resistance by microarray analysis. Mol Med Rep. 2019;19(3):1571-1580. doi: 10.3892/mmr.2018.9774

 

  1. Karadurmus N, Sahin U, Bahadir Basgoz B, Demirer T. Is there a role of high dose chemotherapy and autologous stem cell transplantation in the treatment of Ewing’s sarcoma and osteosarcomas? J Buon. 2018;23(5):1235-1241.

 

  1. Moore DD, Luu HH. Osteosarcoma. Cancer Treat Res. 2014;162:65-92. doi: 10.1007/978-3-319-07323-1_4

 

  1. Tamari K, Hayashi K, Ishii H, et al. Identification of chemoradiation-resistant osteosarcoma stem cells using an imaging system for proteasome activity. Int J Oncol. 2014;45(6):2349-2354. doi: 10.3892/ijo.2014.2671

 

  1. Gorlick R. Current concepts on the molecular biology of osteosarcoma. Cancer Treat Res. 2009;152:467-478. doi: 10.1007/978-1-4419-0284-9_27

 

  1. Gorlick R, Khanna C. Osteosarcoma. J Bone Miner Res. 2010;25(4):683-691. doi: 10.1002/jbmr.77

 

  1. Zhou G, Shi X, Zhang J, Wu S, Zhao J. MicroRNAs in osteosarcoma: From biological players to clinical contributors, a review. J Int Med Res. 2013;41(1):1-12. doi: 10.1177/0300060513475959

 

  1. Du X, Yang J, Yang D, Tian W, Zhu Z. The genetic basis for inactivation of Wnt pathway in human osteosarcoma. BMC Cancer. 2014;14:450. doi: 10.1186/1471-2407-14-450

 

  1. Sun R, Shen J, Gao Y, et al. Overexpression of EZH2is associated with the poor prognosis in osteosarcoma and function analysis indicates a therapeutic potential. Oncotarget. 2016;7(25):38333-38346. doi: 10.18632/oncotarget.9518

 

  1. Li Z, Dou P, Liu T, He S. Application of long noncoding RNAs in osteosarcoma: Biomarkers and therapeutic targets. Cell Physiol Biochem. 2017;42(4):1407-1419. doi: 10.1159/000479205

 

  1. Zhou W, Hao M, Du X, Chen K, Wang G, Yang J. Advances in targeted therapy for osteosarcoma. Discov Med. 2014;17(96):301-307.

 

  1. Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer. 2014;14(11):722-735. doi: 10.1038/nrc3838

 

  1. Chen X, Bahrami A, Pappo A, et al. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 2014;7(1):104-112. doi: 10.1016/j.celrep.2014.03.003

 

  1. Gao Y, Luo LH, Li S, Yang C. miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem Biophys Res Commun.2014;444(2):230-234. doi: 10.1016/j.bbrc.2014.01.061

 

  1. Bao YP, Yi Y, Peng LL, et al. Roles of microRNA-206 in osteosarcoma pathogenesis and progression. Asian Pac J Cancer Prev. 2013;14(6):3751-3755. doi: 10.7314/apjcp.2013.14.6.3751

 

  1. Cai H, Zhao H, Tang J, Wu H. Serum miR-195 is a diagnostic and prognostic marker for osteosarcoma. J Surg Res. 2015;194(2):505-510.doi: 10.1016/j.jss.2014.11.025

 

  1. Su M, Xiao Y, Ma J, et al. Long non-coding RNAs in esophageal cancer: Molecular mechanisms, functions, and potential applications. J Hematol Oncol. 2018;11(1):118. doi: 10.1186/s13045-018-0663-8

 

  1. Jiang C, Li X, Zhao H, Liu H. Long non-coding RNAs: Potential new biomarkers for predicting tumor invasion and metastasis. Mol Cancer. 2016;15(1):62. doi: 10.1186/s12943-016-0545-z

 

  1. Sun XH, Yang LB, Geng XL, Wang R, Zhang ZC. Increased expression of lncRNA HULC indicates a poor prognosis and promotes cell metastasis in osteosarcoma. Int J Clin Exp Pathol. 2015;8(3):2994-3000.

 

  1. Dong Y, Liang G, Yuan B, Yang C, Gao R, Zhou X. MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway. Tumour Biol. 2015;36(3):1477-1486. doi: 10.1007/s13277-014-2631-4

 

  1. Huang X, Zhang W, Pu F, Zhang Z. LncRNA MEG3 promotes chemosensitivity of osteosarcoma by regulatingantitumor immunity via miR-21-5p/p53 pathway and autophagy. Genes Dis. 2023;10(2):531-541. doi: 10.1016/j.gendis.2021.11.004

 

  1. Wang Y, Zeng X, Wang N, et al. Long noncoding RNA DANCR, working as a competitive endogenous RNA, promotes ROCK1-mediated proliferation and metastasis via decoying of miR-335-5p and miR-1972 in osteosarcoma. Mol Cancer. 2018;17(1):89. doi: 10.1186/s12943-018-0837-6

 

  1. Yang D, Liu K, Fan L, et al. LncRNA RP11-361F15.2 promotes osteosarcoma tumorigenesis by inhibiting M2-Like polarization of tumor-associated macrophages of CPEB4. Cancer Lett. 2020;473:33-49. doi: 10.1016/j.canlet.2019.12.041

 

  1. Zheng GH, Fu JR, Xu YH, Jin XQ, Liu WL, Zhou JF. Screening and cloning of multi-drug resistant genes in HL-60/MDR cells. Leuk Res. 2009;33(8):1120-1123. doi: 10.1016/j.leukres.2008.11.018

 

  1. Li S, Jin X, Wu H, et al. HA117 endows HL60 cells with a stem-like signature by inhibiting the degradation of DNMT1 via its ability to down-regulate expression of the GGL domain of RGS6. PLoS One. 2017;12(6):e0180142. doi: 10.1371/journal.pone.0180142

 

  1. Duan W, Jin X, Xiu Y, et al. Expression of the novel all-transretinoic acid-related resistance gene HA117 in pediatric solid tumors. J Pediatr Hematol Oncol. 2014;36(1):45-50. doi: 10.1097/MPH.0b013e31828e5d73

 

  1. Ho XD, Phung P, Le VQ, et al. Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples. Exp Biol Med (Maywood). 2017;242(18):1802-1811. doi: 10.1177/1535370217736512

 

  1. Chen S, Zhou Y, Chen Y, Gu J. fastp: An ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 2018;34(17):i884-i890. doi: 10.1093/bioinformatics/bty560

 

  1. Kim D, Paggi JM, Park C, Bennett C, Salzberg SL. Graphbased genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol. 2019;37(8):907-915. doi: 10.1038/s41587-019-0201-4

 

  1. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 2009;10(3):R25. doi: 10.1186/gb-2009-10-3-r25

 

  1. Li B, Dewey CN. RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011;12:323. doi: 10.1186/1471-2105-12-323

 

  1. Robinson MD, McCarthy DJ, Smyth GK. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139-140. doi: 10.1093/bioinformatics/btp616

 

  1. Li J, Ma W, Zeng P, et al. LncTar: A tool for predicting the RNA targets of long noncoding RNAs. Brief Bioinform. 2015;16(5):806-812. doi: 10.1093/bib/bbu048

 

  1. Shannon P, Markiel A, Ozier O, et al. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-2504. doi: 10.1101/gr.1239303

 

  1. Gillespie M, Jassal B, Stephan R, et al. The reactome pathway knowledgebase 2022. Nucleic Acids Res. 2022;50(D1):D687-D692. doi: 10.1093/nar/gkab1028

 

  1. Sherman BT, Hao M, Qiu J, et al. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50(W1):W216-W221. doi: 10.1093/nar/gkac194

 

  1. Ito K, Murphy D. Application of ggplot2 to pharmacometrics graphics. CPT Pharmacometrics Syst Pharmacol. 2013;2(10):e79. doi: 10.1038/psp.2013.56

 

  1. Gyorffy B, Lánczky A, Szállási Z. Implementing an online tool for genome-wide validation of survival-associated biomarkers in ovarian-cancer using microarray data from 1287 patients. Endocr Relat Cancer. 2012;19(2):197-208. doi: 10.1530/erc-11-0329

 

  1. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi: 10.1186/s13059-014-0550-8

 

  1. McAndrews KM, Kalluri R. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019;18(1):52. doi: 10.1186/s12943-019-0963-9

 

  1. Syn NL, Wang L, Chow EK, Lim CT, Goh BC. Exosomes in cancer nanomedicine and immunotherapy: Prospects and challenges. Trends Biotechnol. 2017;35(7):665-676. doi: 10.1016/j.tibtech.2017.03.004

 

  1. Wu M, Wang G, Hu W, Yao Y, Yu XF. Emerging roles and therapeutic value of exosomes in cancer metastasis. Mol Cancer. 2019;18(1):53. doi: 10.1186/s12943-019-0964-8

 

  1. Sha L, Ma D, Chen C. Exosome-mediated Hic-5 regulates proliferation and apoptosis of osteosarcoma via Wnt/β-catenin signal pathway. Aging (Albany NY). 2020;12(23):23598-23608. doi: 10.18632/aging.103546

 

  1. Jiang M, Jike Y, Liu K, et al. Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1. Mol Cancer. 2023;22(1):113. ,doi: 10.1186/s12943-023-01804-z

 

  1. Lindström MS. Elucidation of motifs in ribosomal protein S9 that mediate its nucleolar localization and binding toNPM1/nucleophosmin. PLoS One. 2012;7(12):e52476. doi: 10.1371/journal.pone.0052476

 

  1. Lindström MS, Zhang Y. Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation. J Biol Chem. 2008;283(23):15568-15576. doi: 10.1074/jbc.M801151200

 

  1. Cheng DD, Zhu B, Li SJ, Yuan T, Yang QC, Fan CY. Downregulation of RPS9 inhibits osteosarcoma cell growth through inactivation of MAPK signaling pathway. J Cancer. 2017;8(14):2720-2728. ,doi: 10.7150/jca.19130

 

  1. Li S, Hu T, Yuan T, Cheng D, Yang Q. Nucleoside diphosphate kinase B promotes osteosarcoma proliferation through c-Myc. Cancer Biol Ther. 2018;19(7):565-572. ,doi: 10.1080/15384047.2017.1416273

 

  1. Feng XT, Wang C, Zhang FJ, Wu XQ, Zhang Z. MicroRNA1274a serves as a prognostic biomarker in patients with osteosarcoma and is involved in tumor progression via targeting ADAM9. J Biol Regul Homeost Agents. 2021;35(1):151-160. doi: 10.23812/20-695-a

 

  1. Zhao R, Chen S, Cui W, et al. PTPN1 is a prognostic biomarker related to cancer immunity and drug sensitivity: From pan-cancer analysis to validation in breast cancer. Front Immunol. 2023;14:1232047. doi: 10.3389/fimmu.2023.1232047

 

  1. Glubb DM, Maranian MJ, Michailidou K, et al. Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1. Am J Hum Genet. 2015;96(1):5-20. doi: 10.1016/j.ajhg.2014.11.009

 

  1. Cuevas BD, Winter-Vann AM, Johnson NL, Johnson GL. MEKK1 controls matrix degradation and tumor cell dissemination during metastasis of polyoma middle-T driven mammary cancer. Oncogene. 2006;25(36):4998-5010. doi: 10.1038/sj.onc.1209507

 

  1. Ding L, Congwei L, Bei Q, et al. mTOR: An attractive therapeutic target for osteosarcoma? Oncotarget. 2016;7(31):50805-50813. doi: 10.18632/oncotarget.9305

 

  1. Li J, Su L, Xiao X, et al. Development and validation of novel prognostic models for immune-related genes in osteosarcoma. Front Mol Biosci. 2022;9:828886. doi: 10.3389/fmolb.2022.828886

 

  1. Posner BA, Gilman AG, Harris BA. Regulators of G protein signaling 6 and 7. Purification of complexes with gbeta5 and assessment of their effects on g protein-mediated signaling pathways. J Biol Chem. 1999;274(43):31087-31093. doi: 10.1074/jbc.274.43.31087

 

  1. Liu Z, Fisher RA. RGS6 interacts with DMAP1 and DNMT1 and inhibits DMAP1 transcriptional repressor activity. J Biol Chem. 2004;279(14):14120-14128. doi: 10.1074/jbc.M309547200

 

  1. Luo Y, Li S, Teng Y, et al. Differential expression of FOXA1, DUSP6, and HA117 in colon segments of Hirschsprung’s disease. Int J Clin Exp Pathol. 2015;8(4):3979-3986.
Share
Back to top
Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept