Skip to content
2000
image of TSPOAP1-AS1: A Novel Biomarker for the Prognosis and Therapeutic Target in Cervical Cancer

Abstract

Background

TSPOAP1 antisense RNA 1 (TSPOAP1-AS1) is a long non-coding RNA (lncRNA) that has received widespread attention in oncology research in recent years. Its role and mechanism in some cancers have gradually been revealed. However, it is not clear what role TSPOAP1-AS1 plays in cervical cancer (CESC).

Objective

In this study, bioinformatic analysis and experimental validation were carried out to investigate the relationship between TSPOAP1-AS1 and CESC.

Methods

The relationships between clinical characteristics in patients with CESC, TSPOAP1-AS1 expression, prognostic factors, regulation network, and immune infiltration of TSPOAP1-AS1 were evaluated using statistics and The Cancer Genome Atlas database. Real-Time Quantitative Reverse Transcription PCR was used to test TSPOAP1-AS1, miR-17-5p, and AGFG2 expression in CESC cell lines.

Results

CESC patients exhibited markedly reduced expression of TSPOAP1-AS1. There was a significant correlation between low expression of TSPOAP1-AS1 in CESC patients and the clinical stage ( 0.05), weight ( 0.05), and BMI ( 0.05). Lower expression of TSPOAP1-AS1 in patients with CESC was associated with poorer overall survival (OS) (p = 0.014) and disease-specific survival (DSS) (p = 0.030). There was also an independent correlation between high expression of TSPOAP1-AS1 (p = 0.036) and DSS in patients with CESC. TSPOAP1-AS1 was involved in the ribosome, oxidative phosphorylation, antigen processing and presentation, cell adhesion molecules (CAMs), the chemokine signaling pathway, neuroactive ligand-receptor interaction, and primary immunodeficiencies. The infiltration of immune cells and the expression of TSPOAP1-AS1 were found to be correlated. A ceRNA network of TSPOAP1-AS1/miR-17-5p/AGFG2 was constructed in CESC. In CESC, a ceRNA network involving TSPOAP1-AS1/miR-17-5p/AGFG2 was successfully established. When comparing CESC cell lines with HcerEpic, the expression of TSPOAP1-AS1 and AGFG2 decreased significantly, and the expression of miR-17-5p increased significantly.

Conclusion

In CESC patients, low expression of TSPOAP1-AS1 was associated with poor survival and immune infiltration. It may be effective to use TSPOAP1-AS1 as a biomarker of prognosis and therapeutic target in CESC.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073355878241117153320
2025-01-13
2025-09-14

  • From This Site

    /content/journals/cchts/10.2174/0113862073355878241117153320
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Boon S.S. Luk H.Y. Xiao C. Chen Z. Chan P.K.S. Review of the standard and advanced screening, staging systems and treatment modalities for cervical cancer. Cancers (Basel) 2022 14 12 2913 35740578
    [Google Scholar]
  2. Zhang Y. Wang H. Lu J. Lv Q. Yun B. Ge Z. Yan L. Down-regulation of S1PR2 is correlated with poor prognosis and immune infiltrates in cervical squamous cell carcinoma and endocervical adenocarcinoma. Int. J. Immunopathol. Pharmacol. 2023 37 3946320231178131 37232164
    [Google Scholar]
  3. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. 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 33538338
    [Google Scholar]
  4. Arbyn M. Weiderpass E. Bruni L. de Sanjosé S. Saraiya M. Ferlay J. Bray F. Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob. Health 2020 8 2 e191 e203 31812369
    [Google Scholar]
  5. Jia Q. Wang H. Xiao X. Sun Y. Tan X. Chai J. Yang Y. Yin Z. Li M. Wang K. Liu J. UCHL1 acts as a prognostic factor and promotes cancer stemness in cervical squamous cell carcinoma. Pathol. Res. Pract. 2023 247 154574 37257242
    [Google Scholar]
  6. Pan H. Liu Q. Zhang F. Wang X. Wang S. Shi X. High STK40 expression as an independent prognostic biomarker and correlated with immune infiltrates in low-grade gliomas. Int. J. Gen. Med. 2021 14 6389 6400 34675607
    [Google Scholar]
  7. Zhao Y.C. Wang T.J. Qu G.H. She L.Z. Cui J. Zhang R.F. Qu H.D. TPM3: A novel prognostic biomarker of cervical cancer that correlates with immune infiltration and promotes malignant behavior in vivo and in vitro. Am. J. Cancer Res. 2023 13 7 3123 3139 37559998
    [Google Scholar]
  8. Jarroux J. Morillon A. Pinskaya M. History, discovery, and classification of lncRNAs. Adv. Exp. Med. Biol. 2017 1008 1 46 28815535
    [Google Scholar]
  9. Zhao W. Qin P. Zhang D. Cui X. Gao J. Yu Z. Chai Y. Wang J. Li J. Long non-coding RNA PVT1 encapsulated in bone marrow mesenchymal stem cell-derived exosomes promotes osteosarcoma growth and metastasis by stabilizing ERG and sponging miR-183-5p. Aging (Albany NY) 2019 11 21 9581 9596 31699956
    [Google Scholar]
  10. Wang X. Li L. Zhao K. Lin Q. Li H. Xue X. Ge W. He H. Liu D. Xie H. Wu Q. Hu Y. A novel LncRNA HITT forms a regulatory loop with HIF-1α to modulate angiogenesis and tumor growth. Cell Death Differ. 2020 27 4 1431 1446 31700144
    [Google Scholar]
  11. Zhou H.J. Wang L.Q. Wang D.B. Yu J.B. Zhu Y. Xu Q.S. Zheng X.J. Zhan R.Y. Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKβ/NF-κB signaling pathway. Am. J. Physiol. Cell Physiol. 2018 315 1 C52 C61 29631367
    [Google Scholar]
  12. Liu H. Liu L. Liu Q. He F. Zhu H. LncRNA HOXD-AS1 affects proliferation and apoptosis of cervical cancer cells by promoting FRRS1 expression via transcription factor ELF1. Cell Cycle 2022 21 4 416 426 34985386
    [Google Scholar]
  13. Song Y. Pan H. Yang L. Fan Y. Zhang H. Pan M. Zhang Y. DGUOK-AS1 promotes cervical squamous cell carcinoma progression by suppressing miR-499a-5p that targets SPRR1B in vitro. Biochem. Biophys. Res. Commun. 2021 585 177 184 34808501
    [Google Scholar]
  14. Zeng J. Ma Y.X. Liu Z.H. Zeng Y.L. LncRNA SNHG7 contributes to cell proliferation, invasion and prognosis of cervical cancer. Eur. Rev. Med. Pharmacol. Sci. 2019 23 21 9277 9285 31773679
    [Google Scholar]
  15. Cai Y. Huang Y. Zhang J. Liu X. Zhao F. Zhang K. Xu S. Yang Y. Huang H. Gao Y. LncRNA CBR3-AS1 predicts a poor prognosis and promotes cervical cancer progression through the miR-3163/LASP1 pathway. Neoplasma 2022 69 6 1406 1417 36591804
    [Google Scholar]
  16. Naizhaer G. Kuerban A. Meilipa Kuerban R. Zhou P. Up-regulation of lncRNA FALEC indicates prognosis and diagnosis values in cervical cancer. Pathol. Res. Pract. 2019 215 8 152495 31248657
    [Google Scholar]
  17. Ma C. Li F. Gu Z. Yang Y. Qi Y. A novel defined risk signature of cuproptosis-related long non-coding RNA for predicting prognosis, immune infiltration, and immunotherapy response in lung adenocarcinoma. Front. Pharmacol. 2023 14 1146840 37670938
    [Google Scholar]
  18. Tian J. Wang Y. The lncRNAs MIR600HG and TSPOAP1-AS1 may potentially act as biomarkers for predicting pancreatic cancer. Transl. Cancer Res. 2020 9 2 809 817 35117426
    [Google Scholar]
  19. Zhao Z. Fang Q. Wei L. Lin J. Su R. Li N. Autophagy-related gene CXCR4 is a potential predictor of prognosis and immunotherapy response for gastric cancer. Discov. Med. 2023 35 179 1190 1201 38058084
    [Google Scholar]
  20. Li L. Zou W. Xiao Z. Deng Z. Liu R. Hypoxia-induced long non-coding RNA LSAMP-AS1 regulates cerna network to predict prognosis for pancreatic cancer. Comb. Chem. High Throughput Screen. 2023 26 13 2358 2371 36918789
    [Google Scholar]
  21. Shu W. Wang Z. Zhang W. Zhang J. Zhao R. Yu Z. Dong K. Wang H. Identification of EMT-associated LncRNA signature for predicting the prognosis of patients with endometrial cancer. Comb. Chem. High Throughput Screen. 2023 26 8 1488 1502 36200154
    [Google Scholar]
  22. Chen B. Ding X. Wan A. Qi X. Lin X. Wang H. Mu W. Wang G. Zheng J. Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer. Sci. Rep. 2023 13 1 16244 37758722
    [Google Scholar]
  23. Chen B. Lu X. Zhou Q. Chen Q. Zhu S. Li G. Liu H. PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer. PLoS One 2023 18 8 e0290031 37582104
    [Google Scholar]
  24. Guo J. Feng S. Liu H. Chen Z. Ding C. Jin Y. Chen X. Ling Y. Zeng Y. Long H. Qiu H. TRIM6: An upregulated biomarker with prognostic significance and immune correlations in gliomas. Biomolecules 2023 13 9 1298 37759698
    [Google Scholar]
  25. Gkirgkiris K. Papoutsi E. Athanasiou N. Gκoufas S. Siempos I.I. Drug-overdose associated acute hypoxemic respiratory failure: A secondary analysis. Pneumon 2024 37 1 1 8
    [Google Scholar]
  26. Chen H. Jiang Z. Yang B. Yan G. Wang X. Zang S. Exploring prognostic signatures of hepatocellular carcinoma and the potential implications in tumor immune microenvironment. Comb. Chem. High Throughput Screen. 2022 25 6 998 1004 33687891
    [Google Scholar]
  27. Wang S Zhou L Ji N Sun C Sun L Sun J Targeting ACYP1-mediated glycolysis reverses lenvatinib resistance and restricts hepatocellular carcinoma progression. Drug Resist Updat. 2023 69 100976
    [Google Scholar]
  28. Lu R. Li Y. Xieyidai A. Yu T. Feng Y. Exploring the role of DKK1 in the occurrence of lung adenocarcinoma based on the analysis of bioinformatics. Zhongguo Fei Ai Za Zhi 2023 26 8 579 590 37752538
    [Google Scholar]
  29. Liu J. Lichtenberg T. Hoadley K.A. Poisson L.M. Lazar A.J. Cherniack A.D. Kovatich A.J. Benz C.C. Levine D.A. Lee A.V. Omberg L. Wolf D.M. Shriver C.D. Thorsson V. Hu H. An integrated TCGA pan-cancer clinical data resource to drive high-quality survival outcome analytics. Cell 2018 173 2 400 416.e11 29625055
    [Google Scholar]
  30. Li Z. Wang H. Deng X. Zhang J. Wang L. Tang W. You W. Nian W. Construction and validation of an immune-related lncRNA prognosis model for thyroid cancer. Comb. Chem. High Throughput Screen. 2022 25 13 2217 2227 35209814
    [Google Scholar]
  31. Liang W. Lu Y. Pan X. Zeng Y. Zheng W. Li Y. Nie Y. Li D. Wang D. Decreased expression of a novel lncRNA FAM181A-AS1 is associated with poor prognosis and immune infiltration in lung adenocarcinoma. Pharm. Genomics Pers. Med. 2022 15 985 998 36482943
    [Google Scholar]
  32. Tao S. Cui D. Cheng H. Liu X. Jiang Z. Chen H. Gao Y. High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma. BMC Cancer 2024 24 1 194 38347489
    [Google Scholar]
  33. Li Q. Wei K. Zhang X. Lv Y. Li M. Zhou C. Su S. Hou D. Hou J. TIMP1 shapes an immunosuppressive microenvironment by regulating anoikis to promote the progression of clear cell renal cell carcinoma. Aging (Albany NY) 2023 15 17 8908 8929 37688768
    [Google Scholar]
  34. Zhan Z. Ye M. Jin X. The roles of FLOT1 in human diseases (Review). Mol. Med. Rep. 2023 28 5 212 [Review]. 37772385
    [Google Scholar]
  35. Ma X.L. Nie Y.Y. Xie S.H. Zheng H. Tong Y. Wang Y.C. Yan T.Q. Meng X. Cao J.Z. Tang W.G. Guo L. Lu R.Q. ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma. Exp. Hematol. Oncol. 2023 12 1 38 37061723
    [Google Scholar]
  36. Xie H. Wu Z. Li Z. Huang Y. Zou J. Zhou H. Significance of ZEB2 in the immune microenvironment of colon cancer. Front. Genet. 2022 13 995333 36072677
    [Google Scholar]
  37. Chen T. Zhu C. Wang X. Pan Y. LncRNA ELF3-AS1 is a prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma. Can. J. Gastroenterol. Hepatol. 2021 2021 8323487 34336727
    [Google Scholar]
  38. Liu F. Li X. Zhou X. Tong H. Hu Z. Bai X. Gou X. A novel hypoxia-related lncRNA risk score model for prognosis evaluation of clear cell renal cell carcinoma. Comb. Chem. High Throughput Screen. 2023 Epub ahead of print 37282651
    [Google Scholar]
  39. Wang T. Cheng M.Y. Shan M.Y. Tang C.Y. Pan N.J. Xu Z.H. Tang X.L. Construction of a competitive endogenous RNA network related to exosomes in diabetic retinopathy. Comb. Chem. High Throughput Screen. 2023 26 3 576 588 35692142
    [Google Scholar]
  40. Zhang L. Qian Y. An epithelial-mesenchymal transition-related prognostic model for colorectal cancer based on weighted gene co-expression network analysis. J. Int. Med. Res. 2022 50 12 3000605221140683 36510452
    [Google Scholar]
  41. Hänzelmann S. Castelo R. Guinney J. GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics 2013 14 7 23323831
    [Google Scholar]
  42. Bindea G. Mlecnik B. Tosolini M. Kirilovsky A. Waldner M. Obenauf A.C. Angell H. Fredriksen T. Lafontaine L. Berger A. Bruneval P. Fridman W.H. Becker C. Pagès F. Speicher M.R. Trajanoski Z. Galon J. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 2013 39 4 782 795 24138885
    [Google Scholar]
  43. Cai H. Chen S. Wu Z. Wang F. Tang S. Li D. Wang D. Guo W. Comprehensive analysis of ZNF692 as a potential biomarker associated with immune infiltration in a pan cancer analysis and validation in hepatocellular carcinoma. Aging (Albany NY) 2023 15 22 13041 13058 37980166
    [Google Scholar]
  44. Yoshihara K. Shahmoradgoli M. Martínez E. Vegesna R. Kim H. Torres-Garcia W. Treviño V. Shen H. Laird P.W. Levine D.A. Carter S.L. Getz G. Stemke-Hale K. Mills G.B. Verhaak R.G. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 2013 4 2612 24113773
    [Google Scholar]
  45. Liu S. Jiang X. Li W. Cao D. Shen K. Yang J. Inhibition of the long non-coding RNA MALAT1 suppresses tumorigenicity and induces apoptosis in the human ovarian cancer SKOV3 cell line. Oncol. Lett. 2016 11 6 3686 3692 27313681
    [Google Scholar]
  46. Wang Y. Li G. Wang Z. Wang W. Wang X. Luo X. Zhao J. Li F. Bian L. Multi-omics analysis of LAMB3 as a potential immunological and biomarker in pan-cancer. Front. Mol. Biosci. 2023 10 1157970 37577750
    [Google Scholar]
  47. Sun J. Zhu S. Identifying the role of hypoxia-related lncRNAs in pancreatic cancer. Genomics 2023 115 5 110665 37315872
    [Google Scholar]
  48. Ma X. Fu T. Ke Z.Y. Du S.L. Wang X.C. Zhou N. Zhong M.Y. Liu Y.J. Liang A.L. MiR-17- 5p/RRM2 regulated gemcitabine resistance in lung cancer A549 cells. Cell Cycle 2023 22 11 1367 1379 37115505
    [Google Scholar]
  49. Si C. Yang L. Cai X. LncRNA LINC00649 aggravates the progression of cervical cancer through sponging miR-216a-3p. J. Obstet. Gynaecol. Res. 2022 48 11 2853 2862 36054700
    [Google Scholar]
  50. Yang B. Wang Z. Deng Y. Xiao L. Zhang K. LncRNA LAMTOR5-AS1 sponges miR-210-3p and regulates cervical cancer progression. J. Obstet. Gynaecol. Res. 2022 48 12 3171 3178 36173004
    [Google Scholar]
  51. Guan H.M. Li W.Q. Liu J. Zhou J.Y. LncRNA HIF1A-AS2 modulated by HPV16 E6 regulates apoptosis of cervical cancer cells via P53/caspase9/caspase3 axis. Cell. Signal. 2022 97 110390 35728704
    [Google Scholar]
  52. Yao H. Jiang X. Fu H. Yang Y. Jin Q. Zhang W. Cao W. Gao W. Wang S. Zhu Y. Ying J. Tian L. Chen G. Tong Z. Qi J. Zhou S. Exploration of the immune-related long noncoding RNA prognostic signature and inflammatory microenvironment for cervical cancer. Front. Pharmacol. 2022 13 870221 35662687
    [Google Scholar]
  53. Wang Q. Zhang D. Feng W. Guo Y. Sun X. Zhang M. Guan Z. Duan M. Long noncoding RNA TSPOAP1 antisense RNA 1 negatively modulates type I IFN signaling to facilitate influenza A virus replication. J. Med. Virol. 2022 94 2 557 566 30968963
    [Google Scholar]
  54. Yim N.H. Cha M.H. Kim M.S. Hypermethylation of the TSPOAP1-AS1 promoter may be associated with obesity in overweight/obese korean subjects. Int. J. Mol. Sci. 2020 21 9 3307 32392798
    [Google Scholar]
  55. Gao H. Liu Y. Hu Y. Ge M. Ding J. Ye Q. Establishment and application of a prognostic risk score model based on characteristics of different immunophenotypes for lung adenocarcinoma. Front. Genet. 2022 13 850101 35547263
    [Google Scholar]
  56. Temaj G. Chichiarelli S. Eufemi M. Altieri F. Hadziselimovic R. Farooqi A.A. Yaylim I. Saso L. Ribosome-directed therapies in cancer. Biomedicines 2022 10 9 2088 36140189
    [Google Scholar]
  57. Jonsson M. Fjeldbo C.S. Holm R. Stokke T. Kristensen G.B. Lyng H. Mitochondrial function of CKS2 oncoprotein links oxidative phosphorylation with cell division in chemoradioresistant cervical cancer. Neoplasia 2019 21 4 353 362 30856376
    [Google Scholar]
  58. Qin Y. Ekmekcioglu S. Forget M.A. Szekvolgyi L. Hwu P. Grimm E.A. Jazaeri A.A. Roszik J. Cervical cancer neoantigen landscape and immune activity is associated with human papillomavirus master regulators. Front. Immunol. 2017 8 689 28670312
    [Google Scholar]
  59. D’Arcy C. Kiel C. Cell adhesion molecules in normal skin and melanoma. Biomolecules 2021 11 8 1213 34439879
    [Google Scholar]
  60. Ruan Y. Chen L. Xie D. Luo T. Xu Y. Ye T. Chen X. Feng X. Wu X. Mechanisms of cell adhesion molecules in endocrine-related cancers: A Concise outlook. Front. Endocrinol. (Lausanne) 2022 13 865436 35464064
    [Google Scholar]
  61. Khare T. Bissonnette M. Khare S. CXCL12-CXCR4/CXCR7 axis in colorectal cancer: Therapeutic target in preclinical and clinical studies. Int. J. Mol. Sci. 2021 22 14 7371 34298991
    [Google Scholar]
  62. Yang Y. Li J. Jing C. Zhai Y. Bai Z. Yang Y. Deng W. Inhibition of neuroactive ligand-receptor interaction pathway can enhance immunotherapy response in colon cancer: An in silico study. Expert Rev. Anticancer Ther. 2023 23 11 1205 1215 37555253
    [Google Scholar]
  63. Derpoorter C. Bordon V. Laureys G. Haerynck F. Lammens T. Genes at the crossroad of primary immunodeficiencies and cancer. Front. Immunol. 2018 9 2544 30443258
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073355878241117153320
Loading
TSPOAP1-AS1: A Novel Biomarker for the Prognosis and Therapeutic Target in Cervical Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0113862073355878241117153320
/content/journals/cchts/10.2174/0113862073355878241117153320
/content/journals/cchts/10.2174/0113862073355878241117153320
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: ceRNA ; biomarker ; TSPOAP1-AS1 ; prognosis ; immune infiltration ; cervical cancer

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test