The circular RNAs differential expression profiles in the metastasis of salivary adenoid cystic carcinoma cells

Abstract

In order to reveal circular RNAs (circRNAs) differential expression profiles and investigate the function and mechanism of circRNAs in the metastasis of salivary adenoid cystic carcinoma (SACC), microarray was used to detect differentially expressed circRNAs in SACC-83 and SACC-lung metastasis (LM) cell lines. Up-regulated circRNAs were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to further predict their function. Expression of candidate circRNA and microRNA (miRNA) was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Constructed circRNA–miRNA–mRNA co-expression network was based on TargetScan, miRanda databases. Wound healing and transwell assays were completed to examine the effects of hsa_circRNA_001982 and miR-181a-5p on cell migration and invasion. qRT-PCR confirmed hsa_circRNA_092556, hsa_circRNA_101379, and hsa_circRNA_001982 up-regulation in SACC-LM. miR-181a-5p was down-regulated in SACC-LM and correlated with up-regulated hsa_circRNA_001982. Wound healing and transwell assays indicated that silencing hsa_circRNA_001982 inhibited the migration and invasion of the SACC-LM cells. Furthermore, over-expression of hsa_circRNA_001982 promoted the migration and invasion of SACC-83 cells. Interestingly, up-regulation or down-regulation of miR-181a-5p led to the opposite result in wound healing and transwell assays. Overall, differential expression circRNA profiles in SACC-83 and SACC-LM cells may reveal potential targets and a novel mechanism of circRNAs in the metastasis of SACC. Moreover, the interaction of hsa_circRNA_001982/miR-181a-5p is closely related to the metastasis of SACC cells.

This is a preview of subscription content, access via your institution.

Fig. 1

source distribution. circRNAs were widely generated from all chromosomes excluding sex chromosome Y. f The pie chart summarizes the percentage of five types of circRNAs analyzed by microarray. The majority were exonic circRNAs, which refers to circRNA containing the exons of the linear transcript

Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

circRNA:

Circular RNA

ncRNA:

Non-coding RNA

SACC:

Salivary adenoid cystic carcinoma

LM:

Lung metastasis

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

miRNA:

MicroRNA

qRT-PCR:

Quantitative real-time polymerase chain reaction

FBS:

Fetal bovine serum

cDNA:

Complementary DNA

siRNAs:

Small interfering RNAs

PBS:

Phosphate-buffered saline

SD:

Standard deviation

MREs:

MiRNA response elements

References

  1. 1.

    Laurie SA, Ho AL, Fury MG et al (2011) Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review. Lancet Oncol 12(8):815–824

    CAS  Article  Google Scholar 

  2. 2.

    Hanna GJ, Bae JE, Lorch JH et al (2020) Long-term outcomes and clinicogenomic correlates in recurrent, metastatic adenoid cystic carcinoma. Oral Oncol 106:104690

    CAS  Article  Google Scholar 

  3. 3.

    Yang WW, Yang LQ, Zhao F et al (2017) Epiregulin promotes lung metastasis of salivary adenoid cystic carcinoma. Theranostics 7(15):3700–3714

    CAS  Article  Google Scholar 

  4. 4.

    Jiang YP, Tang YL, Wang SS et al (2020) PRRX1-induced epithelial-to-mesenchymal transition in salivary adenoid cystic carcinoma activates the metabolic reprogramming of free fatty acids to promote invasion and metastasis. Cell Prolif 53(1):e12705

    PubMed  Google Scholar 

  5. 5.

    Atallah S, Casiraghi O, Fakhry N et al (2020) A prospective multicentre REFCOR study of 470 cases of head and neck adenoid cystic carcinoma: epidemiology and prognostic factors. Eur J Cancer 130:241–249

    CAS  Article  Google Scholar 

  6. 6.

    Fordice J, Kershaw C, El-Naggar A et al (1999) Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg 125(2):149–152

    CAS  Article  Google Scholar 

  7. 7.

    Wang HF, Wang SS, Zheng M et al (2019) Hypoxia promotes vasculogenic mimicry formation by vascular endothelial growth factor A mediating epithelial–mesenchymal transition in salivary adenoid cystic carcinoma. Cell Prolif 52(3):e12600

    Article  Google Scholar 

  8. 8.

    Van der Wal JE, Becking AG, Snow GB et al (2002) Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up. Head Neck 24(8):779–783

    Article  Google Scholar 

  9. 9.

    Meng N, Chen M, Chen D et al (2020) Small protein hidden in lncRNALOC90024 promotes “Cancerous” RNA splicing and tumorigenesis. Adv Sci (Weinh) 7(10):1903233

    CAS  Article  Google Scholar 

  10. 10.

    Brusa R, Magri F, Bresolin N et al (2020) Noncoding RNAs in Duchenne and Becker muscular dystrophies: role in pathogenesis and future prognostic and therapeutic perspectives. Cell Mol Life Sci. https://doi.org/10.1007/s00018-020-03537-4

    Article  PubMed  Google Scholar 

  11. 11.

    Yang X, Liu M, Li M et al (2020) Epigenetic modulations of noncoding RNA: a novel dimension of cancer biology. Mol Cancer 19(1):64

    Article  Google Scholar 

  12. 12.

    Chen LL (2020) The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Biol. https://doi.org/10.1038/s41580-020-0243-y

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Xiao MS, Ai Y, Wilusz JE (2020) Biogenesis and functions of circular RNAs come into focus. Trends Cell Biol 30(3):226–240

    CAS  Article  Google Scholar 

  14. 14.

    Aufiero S, Reckman YJ, Pinto YM et al (2019) Circular RNAs open a new chapter in cardiovascular biology. Nat Rev Cardiol 16(8):503–514

    Article  Google Scholar 

  15. 15.

    Kristensen LS, Andersen MS, Stagsted LVW et al (2019) The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 20(11):675–691

    CAS  Article  Google Scholar 

  16. 16.

    Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388

    CAS  Article  Google Scholar 

  17. 17.

    Long T, Guo Z, Han L et al (2018) Differential expression profiles of circular RNAs during osteogenic differentiation of mouse adipose-derived stromal cells. Calcif Tissue Int 103(3):338–352

    CAS  Article  Google Scholar 

  18. 18.

    Liu J, Li Z, Teng W et al (2020) Identification of downregulated circRNAs from tissue and plasma of patients with gastric cancer and construction of a circRNA-miRNA-mRNA network. J Cell Biochem. https://doi.org/10.1002/jcb.29673

    Article  PubMed  Google Scholar 

  19. 19.

    Liang L, Zhang L, Zhang J et al (2020) Identification of circRNA-miRNA-mRNA networks for exploring the fundamental mechanism in lung adenocarcinoma. OncoTargets Ther 13:2945–2955

    CAS  Article  Google Scholar 

  20. 20.

    Zhang Q, Wang W, Zhou Q et al (2020) Roles of circRNAs in the tumour microenvironment. Mol Cancer 19(1):14

    CAS  Article  Google Scholar 

  21. 21.

    Cristóbal I, Caramés C, Rubio J et al (2020) Functional and clinical impact of circRNAs in oral cancer. Cancers (Basel) 12(4):1041

    Article  Google Scholar 

  22. 22.

    Zhang L, Zhou Q, Qiu Q et al (2019) CircPLEKHM3 acts as a tumor suppressor through regulation of the miR-9/BRCA1/DNAJB6/KLF4/AKT1 axis in ovarian cancer. Mol Cancer 18(1):144

    CAS  Article  Google Scholar 

  23. 23.

    Wang S, Xia P, Zhang L et al (2019) Systematical identification of breast cancer-related circular RNA modules for deciphering circRNA functions based on the non-negative matrix factorization algorithm. Int J Mol Sci 20(4):919

    CAS  Article  Google Scholar 

  24. 24.

    Chen C, Huang Z, Mo X et al (2020) The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA. J Exp Clin Cancer Res 39(1):91

    CAS  Article  Google Scholar 

  25. 25.

    Luo Z, Rong Z, Zhang J et al (2020) Circular RNA circCCDC9 acts as a miR-6792-3p sponge to suppress the progression of gastric cancer through regulating CAV1 expression. Mol Cancer 19(1):86

    CAS  Article  Google Scholar 

  26. 26.

    Kong Y, Li Y, Luo Y et al (2020) circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer. Mol Cancer 19(1):82

    CAS  Article  Google Scholar 

  27. 27.

    Zhao F, Chen CW, Yang WW et al (2018) hsa_circRNA_0059655 plays a role in salivary adenoid cystic carcinoma by functioning as a sponge of miR-338-3p. Cell Mol Biol (Noisy-le-grand) 64(15):100–106

    Article  Google Scholar 

  28. 28.

    Chen CW, Fu M, Du ZH et al (2020) Long noncoding RNA MRPL23-AS1 promotes adenoid cystic carcinoma lung metastasis. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-19-0819

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sun L, Liu B, Lin Z et al (2015) miR-320a acts as a prognostic factor and Inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3. Mol Cancer 14:96

    Article  Google Scholar 

  30. 30.

    Wang Y, Zhang CY, Xia RH et al (2018) The MYB/miR-130a/NDRG2 axis modulates tumor proliferation and metastatic potential in salivary adenoid cystic carcinoma. Cell Death Dis 9(9):917

    Article  Google Scholar 

  31. 31.

    Bao L, Zhao Y, Liu C et al (2020) The identification of key gene expression signature and biological pathways in metastatic renal cell carcinoma. J Cancer 11(7):1712–1726

    CAS  Article  Google Scholar 

  32. 32.

    Jiramongkol Y, Lam EW (2020) FOXO transcription factor family in cancer and metastasis. Cancer Metastasis Rev. https://doi.org/10.1007/s10555-020-09883-w

    Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Uretmen Kagiali ZC, Sanal E, Karayel Ö et al (2019) Systems-level analysis reveals multiple modulators of epithelial–mesenchymal transition and identifies DNAJB4 and CD81 as novel metastasis inducers in breast cancer. Mol Cell Proteomics 18(9):1756–1771

    Article  Google Scholar 

  34. 34.

    Park S, Kwon W, Park JK et al (2020) Suppression of cathepsin a inhibits growth, migration, and invasion by inhibiting the p38 MAPK signaling pathway in prostate cancer. Arch Biochem Biophys 688:108407

    CAS  Article  Google Scholar 

  35. 35.

    Rodrigues JG, Balmaña M, Macedo JA et al (2018) Glycosylation in cancer: selected roles in tumour progression, immune modulation and metastasis. Cell Immunol 333:46–57

    CAS  Article  Google Scholar 

  36. 36.

    He Q, Zhou X, Li S et al (1830) (2013) MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway. Biochim Biophys Acta 11:5258–5266

    Google Scholar 

  37. 37.

    Tang YY, Zhao P, Zou TN et al (2017) Circular RNA hsa_circ_0001982 promotes breast cancer cell carcinogenesis through decreasing miR-143. DNA Cell Biol 36(11):901–908

    CAS  Article  Google Scholar 

  38. 38.

    Patop IL, Wüst S, Kadener S (2019) Past, present, and future of circRNAs. EMBO J 38(16):e100836

    Article  Google Scholar 

  39. 39.

    Qu S, Yang X, Li X et al (2015) Circular RNA: a new star of noncoding RNAs. Cancer Lett 365(2):141–148

    CAS  Article  Google Scholar 

  40. 40.

    Li Y, Kuscu C, Banach A et al (2015) miR-181a-5p inhibits cancer cell migration and angiogenesis via downregulation of matrix metalloproteinase-14. Cancer Res 75(13):2674–2685

    CAS  Article  Google Scholar 

  41. 41.

    Ma Z, Qiu X, Wang D et al (2015) miR-181a-5p inhibits cell proliferation and migration by targeting Kras in non-small cell lung cancer A549 cells. Acta Biochim Biophys Sin (Shanghai) 47(8):630–638

    CAS  Article  Google Scholar 

  42. 42.

    Shen H, Wang L, Xiong J et al (2019) Long non-coding RNA CCAT1 promotes cervical cancer cell proliferation and invasion by regulating the miR-181a-5p/MMP14 axis. Cell Cycle 18(10):1110–1121

    CAS  Article  Google Scholar 

  43. 43.

    Mao W, Huang X, Wang L et al (2019) Circular RNA hsa_circ_0068871 regulates FGFR3 expression and activates STAT3 by targeting miR-181a-5p to promote bladder cancer progression. J Exp Clin Cancer Res 38(1):169

    Article  Google Scholar 

Download references

Acknowledgements

The authors sincerely appreciate all members participated in this work.

Funding

This study was supported by Grants from the National Nature Science Foundation of China (Nos. 31570950, 10502037 and 31070833), the Science and Technology Foundation of Sichuan Province (Nos. 2017SZ0032, 2010GZ0225, 2011GZ0335 and 2009SZ0139), and National Key Research and Development Program of China (No. 2016YFC1101404).

Author information

Affiliations

Authors

Contributions

Conceived and designed the experiments: JL, RJ, YH, and ZG. Performed the experiments and analyzed the data: RJ, YH, LH, SJ, and LZ. Wrote the manuscript: RJ and ZG. Revising the work: JL. RJ, YH, and ZG were co-first authors.

Corresponding author

Correspondence to Jie Long.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Informed consent All authors are informed and agree to publish.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 14 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ju, R., Huang, Y., Guo, Z. et al. The circular RNAs differential expression profiles in the metastasis of salivary adenoid cystic carcinoma cells. Mol Cell Biochem 476, 1269–1282 (2021). https://doi.org/10.1007/s11010-020-03989-z

Download citation

Keywords

  • circRNA
  • miRNA
  • SACC
  • Expression profiles