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C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2

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Abstract

Recurrence and metastasis are the major factors affecting the survival of nasopharyngeal carcinoma (NPC), and the mechanism remains unclear. Long non-coding RNA chromosome 2 open reading frame 48 (C2orf48) has been shown to influence the prognosis of many cancers. However, C2orf48’s function in NPC has not been clarified. In this investigation, C2orf48 expression in NPC was measured by quantitative real-time PCR (qRT-PCR) at the cellular and tissue levels, and the association between C2orf48 expression and the prognosis of patients with NPC was examined. Additionally, the effects of C2orf48 and high mobility group AT-hook 2 (HMGA2) upon NPC proliferation, migration, and invasion were examined employing the MTT assay, colony formation assay, and transwell assay, respectively. Furthermore, the association between C2orf48 and HMGA2 in NPC was investigated. Our research demonstrated that C2orf48 was overexpressed in NPC tissues and cell lines, and compared to patients with lower levels of C2orf48 expression, those with higher levels had poorer 5-year overall survival and progression-free survival. Functionally, C2orf48 overexpression accelerated NPC cells proliferation, migration, and invasion. Besides, the tandem mass tag (TMT) quantitative proteomic analysis indicated that HMGA2 may be a target of C2orf48. Moreover, upregulation of C2orf48 could increase HMGA2 expression, and HMGA2 silencing could counteract the proliferation, migration, and invasion changes induced by C2orf48 in NPC cells. These results reveal that overexpression of C2orf48 can promote NPC cells proliferation, migration, and invasion via regulating the expression of HMGA2 and C2orf48 may be a potentially important prognostic marker for NPC.

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Data availability

All data used and analyzed in this study are available from the corresponding author on reasonable request.

References

  1. Ho FC, Tham IW, Earnest A, Lee KM, Lu JJ. Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence. BMC Cancer. 2012;12:98. https://doi.org/10.1186/1471-2407-12-98.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Caudell JJ, Gillison ML, Maghami E, Spencer S, Pfister DG, Adkins D, Birkeland AC, Brizel DM, Busse PM, Cmelak AJ, Colevas AD, Eisele DW, Galloway T, Geiger JL, Haddad RI, Hicks WL, Hitchcock YJ, Jimeno A, Leizman D, Mell LK, Mittal BB, Pinto HA, Rocco JW, Rodriguez CP, Savvides PS, Schwartz D, Shah JP, Sher D, St John M, Weber RS, Weinstein G, Worden F, Yang BJ, Yom SS, Zhen W, Burns JL, Darlow SD. NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022. J Natl Comprehensive Cancer Netw JNCCN. 2022;20(3):224–34. https://doi.org/10.6004/jnccn.2022.0016.

    Article  PubMed  Google Scholar 

  3. Herman AB, Tsitsipatis D, Gorospe M. Integrated lncRNA function upon genomic and epigenomic regulation. Mol Cell. 2022;82(12):2252–66. https://doi.org/10.1016/j.molcel.2022.05.027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhang Y, Mao Q, Xia Q, Cheng J, Huang Z, Li Y, Chen P, Yang J, Fan X, Liang Y, Lin H. Noncoding RNAs link metabolic reprogramming to immune microenvironment in cancers. J Hematol Oncol. 2021;14(1):169. https://doi.org/10.1186/s13045-021-01179-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hashemi M, Moosavi MS, Abed HM, Dehghani M, Aalipour M, Heydari EA, Behroozaghdam M, Entezari M, Salimimoghadam S, Gunduz ES, Taheriazam A, Mirzaei S, Samarghandian S. Long non-coding RNA (lncRNA) H19 in human cancer: from proliferation and metastasis to therapy. Pharmacol Res. 2022;184:106418. https://doi.org/10.1016/j.phrs.2022.106418.

    Article  CAS  PubMed  Google Scholar 

  6. Yu C, Li L, Xie F, Guo S, Liu F, Dong N, Wang Y. LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res. 2018;114(1):168–79. https://doi.org/10.1093/cvr/cvx180.

    Article  CAS  PubMed  Google Scholar 

  7. Zheng ZQ, Li ZX, Guan JL, Liu X, Li JY, Chen Y, Lin L, Kou J, Lv JW, Zhang LL, Zhou GQ, Liu RQ, Chen F, He XJ, Li YQ, Li F, Xu SS, Ma J, Liu N, Sun Y. Long Noncoding RNA TINCR-Mediated Regulation of Acetyl-CoA Metabolism Promotes Nasopharyngeal Carcinoma Progression and Chemoresistance. Can Res. 2020;80(23):5174–88. https://doi.org/10.1158/0008-5472.can-19-3626.

    Article  CAS  Google Scholar 

  8. Li ZX, Zheng ZQ, Yang PY, Lin L, Zhou GQ, Lv JW, Zhang LL, Chen F, Li YQ, Wu CF, Li F, Ma J, Liu N, Sun Y. WTAP-mediated m(6)A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. Cell Death Differ. 2022;29(6):1137–51. https://doi.org/10.1038/s41418-021-00905-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang H, Wang W, Fan S. Emerging roles of lncRNA in nasopharyngeal carcinoma and therapeutic opportunities. Int J Biol Sci. 2022;18(7):2714–28. https://doi.org/10.7150/ijbs.70292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang H, Zhuo C, Zhou D, Zhang M, Zhang F, Chen M, Xu S, Chen Z. Small Nucleolar RNA Host Gene 1 (SNHG1) and Chromosome 2 Open Reading Frame 48 (C2orf48) as Potential Prognostic Signatures for Liver Cancer by Constructing Regulatory Networks. Med Sci Monitor. 2020;26:e920482. https://doi.org/10.1265/msm.920482.

    Article  CAS  Google Scholar 

  11. Liu J, Nie S, Liang J, Jiang Y, Wan Y, Zhou S, Cheng W. Competing endogenous RNA network of endometrial carcinoma: a comprehensive analysis. J Cell Biochem. 2019;120(9):15648–60. https://doi.org/10.1002/jcb.28831.

    Article  CAS  PubMed  Google Scholar 

  12. Zhang S, Cao R, Li Q, Yao M, Chen Y, Zhou H. Comprehensive analysis of lncRNA-associated competing endogenous RNA network in tongue squamous cell carcinoma. PeerJ. 2019;7:e6397. https://doi.org/10.7717/peerj.6397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Han P, Chen RH, Wang F, Zeng JY, Yu ST, Xu LH, Cai Q, Liang FY, Xia TL, Lin ZR, Zhong Q, Huang XM. Novel chimeric transcript RRM2-c2orf48 promotes metastasis in nasopharyngeal carcinoma. Cell Death Dis. 2017;8(9):e3047. https://doi.org/10.1038/cddis.2017.402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hock R, Furusawa T, Ueda T, Bustin M. HMG chromosomal proteins in development and disease. Trends Cell Biol. 2007;17(2):72–9. https://doi.org/10.1016/j.tcb.2006.12.001.

    Article  CAS  PubMed  Google Scholar 

  15. Bai J, Yokomizo-Nakano T, Kubota S, Sun Y, Kanai A, Iimori M, Harada H, Iwama A, Sashida G. Overexpression of Hmga2 activates Igf2bp2 and remodels transcriptional program of Tet2-deficient stem cells in myeloid transformation. Oncogene. 2021;40(8):1531–41. https://doi.org/10.1038/s41388-020-01629-w.

    Article  CAS  PubMed  Google Scholar 

  16. Wang X, Wang J, Zhao J, Wang H, Chen J, Wu J. HMGA2 facilitates colorectal cancer progression via STAT3-mediated tumor-associated macrophage recruitment. Theranostics. 2022;12(2):963–75. https://doi.org/10.7150/thno.65411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xia Y, Lv J, Jiang T, Li B, Li Y, He Z, Xuan Z, Sun G, Wang S, Li Z, Wang W, Wang L, Xu Z. CircFAM73A promotes the cancer stem cell-like properties of gastric cancer through the miR-490-3p/HMGA2 positive feedback loop and HNRNPK-mediated β-catenin stabilization. J Exp Clin Cancer Res CR. 2021;40(1):103. https://doi.org/10.1186/s13046-021-01896-9.

    Article  CAS  PubMed  Google Scholar 

  18. Ma J, Kong FF, Yang D, Yang H, Wang C, Cong R, Ma XX. lncRNA MIR210HG promotes the progression of endometrial cancer by sponging miR-337–3p/137 via the HMGA2-TGF-β/Wnt pathway. Mol Ther Nucleic Acids. 2021;24:905–22. https://doi.org/10.1016/j.omtn.2021.04.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wu A, Wu K, Li J, Mo Y, Lin Y, Wang Y, Shen X, Li S, Li L, Yang Z. Let-7a inhibits migration, invasion and epithelial-mesenchymal transition by targeting HMGA2 in nasopharyngeal carcinoma. J Translatl Med. 2015;13:105. https://doi.org/10.1186/s12967-015-0462-8.

    Article  CAS  Google Scholar 

  20. Wang J, Zhong Q, Zhang H, Liu S, Li S, Xia T, Xiao Z, Chen R, Ye Y, Liang F, Han P, Huang X. Nogo-B promotes invasion and metastasis of nasopharyngeal carcinoma via RhoA-SRF-MRTFA pathway. Cell Death Dis. 2022;13(1):76. https://doi.org/10.1038/s41419-022-04518-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tang XR, Li YQ, Liang SB, Jiang W, Liu F, Ge WX, Tang LL, Mao YP, He QM, Yang XJ, Zhang Y, Wen X, Zhang J, Wang YQ, Zhang PP, Sun Y, Yun JP, Zeng J, Li L, Liu LZ, Liu N, Ma J. Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study. Lancet Oncol. 2018;19(3):382–93. https://doi.org/10.1016/s1470-2045(18)30080-9.

    Article  CAS  PubMed  Google Scholar 

  22. Peng WX, Koirala P, Mo YY. LncRNA-mediated regulation of cell signaling in cancer. Oncogene. 2017;36(41):5661–7. https://doi.org/10.1038/onc.2017.184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liang YL, Zhang Y, Tan XR, Qiao H, Liu SR, Tang LL, Mao YP, Chen L, Li WF, Zhou GQ, Zhao Y, Li JY, Li Q, Huang SY, Gong S, Zheng ZQ, Li ZX, Sun Y, Jiang W, Ma J, Li YQ, Liu N. A lncRNA signature associated with tumor immune heterogeneity predicts distant metastasis in locoregionally advanced nasopharyngeal carcinoma. Nat Commun. 2022;13(1):2996. https://doi.org/10.1038/s41467-022-30709-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Li RH, Tian T, Ge QW, He XY, Shi CY, Li JH, Zhang Z, Liu FZ, Sang LJ, Yang ZZ, Liu YZ, Xiong Y, Yan Q, Li X, Ju HQ, Liu J, Wang LJ, Shao JZ, Wang W, Zhou T, Lin A. A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling. Cell Res. 2021;31(10):1088–105. https://doi.org/10.1038/s41422-021-00530-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Li Y, Jiang T, Zhou W, Li J, Li X, Wang Q, Jin X, Yin J, Chen L, Zhang Y, Xu J, Li X. Pan-cancer characterization of immune-related lncRNAs identifies potential oncogenic biomarkers. Nat Commun. 2020;11(1):1000. https://doi.org/10.1038/s41467-020-14802-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang Y, Chen W, Lian J, Zhang H, Yu B, Zhang M, Wei F, Wu J, Jiang J, Jia Y, Mo F, Zhang S, Liang X, Mou X, Tang J. The lncRNA PVT1 regulates nasopharyngeal carcinoma cell proliferation via activating the KAT2A acetyltransferase and stabilizing HIF-1α. Cell Death Differ. 2020;27(2):695–710. https://doi.org/10.1038/s41418-019-0381-y.

    Article  CAS  PubMed  Google Scholar 

  27. Li S, Chen X, Liu X, Yu Y, Pan H, Haak R, Schmidt J, Ziebolz D, Schmalz G. Complex integrated analysis of lncRNAs-miRNAs-mRNAs in oral squamous cell carcinoma. Oral Oncol. 2017;73:1–9. https://doi.org/10.1016/j.oraloncology.2017.07.026.

    Article  CAS  PubMed  Google Scholar 

  28. Kang Z, Yang J. Construction and validation of an autophagy-related long non-coding RNA signature to predict the prognosis of kidney renal papillary cell carcinoma. J Investigative Med. 2022;70(7):1536–44. https://doi.org/10.1136/jim-2022-002379.

    Article  Google Scholar 

  29. Wang X, Yin H, Zhang L, Zheng D, Yang Y, Zhang J, Jiang H, Ling X, Xin Y, Liang H, Fang C, Ma J, Zhu J. The construction and analysis of the aberrant lncRNA-miRNA-mRNA network in non-small cell lung cancer. J Thoracic Dis. 2019;11(5):1772–8. https://doi.org/10.2103/jtd.2019.05.69.

    Article  Google Scholar 

  30. Wu H, Singh S, Xie Z, Li X, Li H. Landscape characterization of chimeric RNAs in colorectal cancer. Cancer Lett. 2020;489:56–65. https://doi.org/10.1016/j.canlet.2020.05.037.

    Article  CAS  PubMed  Google Scholar 

  31. Meisler MH. SCN8A encephalopathy: mechanisms and models. Epilepsia. 2019;60(3):S86-s91. https://doi.org/10.1111/epi.14703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Huang Z, Li H, Huang Q, Chen D, Han J, Wang L, Pan C, Chen W, House MG, Nephew KP, Guo Z. SERPINB2 down-regulation contributes to chemoresistance in head and neck cancer. Mol Carcinog. 2014;53(10):777–86. https://doi.org/10.1002/mc.22033.

    Article  CAS  PubMed  Google Scholar 

  33. Ascenção K, Lheimeur B, Szabo C. Regulation of CyR61 expression and release by 3-mercaptopyruvate sulfurtransferase in colon cancer cells. Redox Biol. 2022;56:102466. https://doi.org/10.1016/j.redox.2022.102466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhang S, Mo Q, Wang X. Oncological role of HMGA2 (Review). Int J Oncol. 2019;55(4):775–88. https://doi.org/10.3892/ijo.2019.4856.

    Article  CAS  PubMed  Google Scholar 

  35. Qiu F, Liu Q, Xia Y, Jin H, Lin Y, Zhao X. Circ_0000658 knockdown inhibits epithelial-mesenchymal transition in bladder cancer via miR-498-induced HMGA2 downregulation. J Exp Clin Cancer Res. 2022;41(1):22. https://doi.org/10.1186/s13046-021-02175-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gao C, Lu W, Lou W, Wang L, Xu Q. Long noncoding RNA HOXC13-AS positively affects cell proliferation and invasion in nasopharyngeal carcinoma via modulating miR-383-3p/HMGA2 axis. J Cell Physiol. 2019;234(8):12809–20. https://doi.org/10.1002/jcp.27915.

    Article  CAS  PubMed  Google Scholar 

  37. Xia YY, Yin L, Tian H, Guo WJ, Jiang N, Jiang XS, Wu J, Chen M, Wu JZ, He X. HMGA2 is associated with epithelial-mesenchymal transition and can predict poor prognosis in nasopharyngeal carcinoma. OncoTargets Ther. 2015;8:169–76. https://doi.org/10.2147/ott.s74397.

    Article  Google Scholar 

  38. Li DK, Chen XR, Wang LN, Wang JH, Li JK, Zhou ZY, Li X, Cai LB, Zhong SS, Zhang JJ, Zeng YM, Zhang QB, Fu XY, Lyu XM, Li MY, Huang ZX, Yao KT. Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis. Cancer Gene Ther. 2022;29(10):1439–51. https://doi.org/10.1038/s41417-022-00453-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Professor Musheng Zeng and Qian Zhong for their selfless assistance on this research, and we also thank the patients who participated in this study.

Funding

This work was supported by the grants from the National Natural Science Foundation of China (No. 81872193 to Xiaoming Huang), and the Natural Science Foundation of Guangdong Province (2023A1515010423 to Xiaoming Huang and 2023A1515030042 to Ping Han).

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Author notes

  1. Yanhui Jiang and Faya Liang have equally contributed to this work.

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 33 Ying Feng Road, Haizhu District, Guangzhou, 510120, China

    Yanhui Jiang, Faya Liang, Renhui Chen, Haicang Zeng, Ping Han & Xiaoming Huang

  2. Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

    Yanhui Jiang

  3. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China

    Yanhui Jiang, Faya Liang, Renhui Chen, Yongsheng Huang, Haicang Zeng, Ping Han & Xiaoming Huang

  4. The Cellular and Molecular Diagnostics Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

    Yongsheng Huang

  5. Department of Otorhinolaryngology, Head and Neck Surgery, Department of Thyroid Center/Thyroid Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

    Zhiwen Xiao

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  1. Yanhui Jiang
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Contributions

All authors contributed to the study conception and design. XH and PH designed and supervised this study. YJ and FL performed the experiments, analyzed the raw data and wrote the first draft of this manuscript. RC and YH collected the samples and clinical data of patients. ZX and HZ performed the statistical analysis. All authors read and approved the final manuscript.

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Correspondence to Ping Han or Xiaoming Huang.

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This study was performed in line with the principles of the Declaration of Helsinki and this project was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital, Sun Yat-sen University (Identifer: SYSKY-2023-357-02).

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Jiang, Y., Liang, F., Chen, R. et al. C2orf48 promotes the progression of nasopharyngeal carcinoma by regulating high mobility group AT-hook 2. Med Oncol 40, 306 (2023). https://doi.org/10.1007/s12032-023-02179-3

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