Skip to main content
Log in

Clinical significance of serum miR-768-3p in HBV-related hepatocellular carcinoma and its potential mechanism

  • Original Article
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

The purpose of this study was to reveal the clinical diagnostic and prognostic value of miR-768-3p in HBV-related HCC and to investigate its effect on the biological function of HCC. Quantitative real-time polymerase chain reaction was used to detect the expression level of miR-768-3p in subjects’ serum. The receiver operating characteristics curve (ROC) evaluated the diagnostic value of miR-768-3p in patients. A Chi-square test was used to analyze the relationship between miR-768-3p and clinical data of patients. Kaplan–Meier survival and Cox regression analysis assessed the prognostic value of miR-768-3p in HCC. Finally, CCK-8 and Transwell assays were used to demonstrate the effect of miR-768-3p on HBV-related HCC function. Serum miR-768-3p was significantly lower in HCC patients than in healthy controls and chronic hepatitis B (CHB) patients. ROC curve suggested that serum miR-768-3p has an important diagnostic value for HBV-related HCC and can significantly differentiate HCC patients from healthy controls, and it can also diagnose HCC patients from CHB patients. Cox analysis confirmed that miR-768-3p was an independent risk factor. Low expression of miR-768-3p was associated with Tumor, Node, Metastasis stage, Barcelona Clinic Liver Cancer stage, and poor prognosis in HCC patients. Finally, cell function experiments confirmed that high expression of miR-768-3p could inhibit cell proliferation, migration, and invasion. All experiments confirmed that miR-768-3p can inhibit the proliferation, migration, and invasion of HBV-related HCC cells, and the low expression of miR-768-3p can be used as a potential diagnostic and prognostic biomarker for HBV-related HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

RFA:

Radiofrequency ablation

AFP:

Alpha-fetoprotein

miRNA:

MicroRNA

CHB:

Chronic hepatitis B

BCLC:

Barcelona Clinic Liver Cancer

FBS:

Fetal bovine serum

qRT-PCR:

Real-time fluorescence quantitative PCR

SD:

Standard deviation

ROC:

Receiver operating characteristic

References

  1. El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.

    Article  CAS  Google Scholar 

  2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  Google Scholar 

  3. Xie Y, Yao Q, Butt AM, et al. Expression profiling of serum microRNA-101 in HBV-associated chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Cancer Biol Ther. 2014;15(9):1248–55.

    Article  CAS  Google Scholar 

  4. Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist. 2010;15(Suppl 4):5–13.

    Article  Google Scholar 

  5. Malaguarnera G, Giordano M, Paladina I, Berretta M, Cappellani A, Malaguarnera M. Serum markers of hepatocellular carcinoma. Dig Dis Sci. 2010;55(10):2744–55.

    Article  CAS  Google Scholar 

  6. Vitale A, Peck-Radosavljevic M, Giannini EG, et al. Personalized treatment of patients with very early hepatocellular carcinoma. J Hepatol. 2017;66(2):412–23.

    Article  Google Scholar 

  7. Mazzoccoli G, Tarquini R, Valoriani A, Oben J, Vinciguerra M, Marra F. Management strategies for hepatocellular carcinoma: old certainties and new realities. Clin Exp Med. 2016;16(3):243–56.

    Article  Google Scholar 

  8. Zhao B, Lu Y, Cao X, et al. MiRNA-124 inhibits the proliferation, migration and invasion of cancer cell in hepatocellular carcinoma by downregulating lncRNA-UCA1. Onco Targets Ther. 2019;12:4509–16.

    Article  CAS  Google Scholar 

  9. Wang Y, Wang CM, Jiang ZZ, et al. MicroRNA-34c targets TGFB-induced factor homeobox 2, represses cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma. Oncol Lett. 2015;10(5):3095–102.

    Article  CAS  Google Scholar 

  10. Du W, Zhang X, Wan Z. miR-3691-5p promotes hepatocellular carcinoma cell migration and invasion through activating PI3K/Akt signaling by targeting PTEN. Onco Targets Ther. 2019;12:4897–906.

    Article  CAS  Google Scholar 

  11. Zhao Q, Sun X, Liu C, Li T, Cui J, Qin C. Expression of the microRNA-143/145 cluster is decreased in hepatitis B virus-associated hepatocellular carcinoma and may serve as a biomarker for tumorigenesis in patients with chronic hepatitis B. Oncol Lett. 2018;15(5):6115–22.

    PubMed  PubMed Central  Google Scholar 

  12. Chen F, Li XF, Fu DS, Huang JG, Yang SE. Clinical potential of miRNA-221 as a novel prognostic biomarker for hepatocellular carcinoma. Cancer Biomark. 2017;18(2):209–14.

    Article  CAS  Google Scholar 

  13. Wang G, Dong F, Xu Z, et al. MicroRNA profile in HBV-induced infection and hepatocellular carcinoma. BMC Cancer. 2017;17(1):805.

    Article  CAS  Google Scholar 

  14. Jiang CC, Croft A, Tseng HY, et al. Repression of microRNA-768-3p by MEK/ERK signalling contributes to enhanced mRNA translation in human melanoma. Oncogene. 2014;33(20):2577–88.

    Article  CAS  Google Scholar 

  15. Vriens MR, Weng J, Suh I, et al. MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer. Cancer. 2012;118(13):3426–32.

    Article  CAS  Google Scholar 

  16. Hepatobiliary Surgery Group, CSoSCMA. Guidelines for surgical treatment of primary hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 2004;13(5):329–30.

    Google Scholar 

  17. Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.

    Article  CAS  Google Scholar 

  18. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60(8):646–9.

    Article  CAS  Google Scholar 

  19. Chen Y, Zhang H, Liao W, et al. FOXP3 gene polymorphism is associated with hepatitis B-related hepatocellular carcinoma in China. J Exp Clin Cancer Res. 2013;32:39.

    Article  CAS  Google Scholar 

  20. Wang F, Xie C, Zhao W, Deng Z, Yang H, Fang Q. Long non-coding RNA CARLo-5 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Clin Exp Med. 2017;17(1):33–43.

    Article  CAS  Google Scholar 

  21. Nagy Á, Lánczky A, Menyhárt O, Győrffy B. Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018;8(1):9227.

    Article  Google Scholar 

  22. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.

    Article  CAS  Google Scholar 

  23. Zubor P, Kubatka P, Dankova Z, et al. miRNA in a multiomic context for diagnosis, treatment monitoring and personalized management of metastatic breast cancer. Future Oncol. 2018;14(18):1847–67.

    Article  CAS  Google Scholar 

  24. Du X, Zhang J, Wang J, Lin X, Ding F. Role of miRNA in lung cancer-potential biomarkers and therapies. Curr Pharm Des. 2018;23(39):5997–6010.

    Article  Google Scholar 

  25. Peng Y, Zhang X, Ma Q, et al. MiRNA-194 activates the Wnt/beta-catenin signaling pathway in gastric cancer by targeting the negative Wnt regulator, SUFU. Cancer Lett. 2017;385:117–27.

    Article  CAS  Google Scholar 

  26. Ye Y, Song Y, Zhuang J, et al. MicroRNA-302a-3p suppresses hepatocellular carcinoma progression by inhibiting proliferation and invasion. Onco Targets Ther. 2018;11:8175–84.

    Article  CAS  Google Scholar 

  27. Wu C, Wang X, Zhang J, et al. MicroRNA-224 expression and polymorphism predict the prognosis of hepatitis b virus-related hepatocellular carcinoma patients after liver resection. Clin Lab. 2019. https://doi.org/10.7754/Clin.Lab.2018.181025.

    Article  PubMed  Google Scholar 

  28. Giray BG, Emekdas G, Tezcan S, et al. Profiles of serum microRNAs; miR-125b-5p and miR223-3p serve as novel biomarkers for HBV-positive hepatocellular carcinoma. Mol Biol Rep. 2014;41(7):4513–9.

    Article  CAS  Google Scholar 

  29. Li S, Yang X, Yang J, Zhen J, Zhang D. Serum microRNA-21 as a potential diagnostic biomarker for breast cancer: a systematic review and meta-analysis. Clin Exp Med. 2016;16(1):29–35.

    Article  Google Scholar 

  30. Meng FL, Wang W, Jia WD. Diagnostic and prognostic significance of serum miR-24-3p in HBV-related hepatocellular carcinoma. Med Oncol. 2014;31(9):177.

    Article  Google Scholar 

  31. Motavaf M, Safari S, Saffari Jourshari M, Alavian SM. Hepatitis B virus-induced hepatocellular carcinoma: the role of the virus x protein. Acta Virol. 2013;57(4):389–96.

    Article  CAS  Google Scholar 

  32. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295(1):65–73.

    Article  CAS  Google Scholar 

  33. Johnson PJ, Melia WM, Palmer MK, Portmann B, Williams R. Relationship between serum alpha-foetoprotein, cirrhosis and survival in hepatocellular carcinoma. Br J Cancer. 1981;44(4):502–5.

    Article  CAS  Google Scholar 

  34. Zhang Z, Han Y, Sun G, Liu X, Jia X, Yu X. MicroRNA-325-3p inhibits cell proliferation and induces apoptosis in hepatitis B virus-related hepatocellular carcinoma by down-regulation of aquaporin 5. Cell Mol Biol Lett. 2019;24:13.

    Article  Google Scholar 

  35. Xie Z, Chen W, Chen Y, Wang X, Gao W, Liu Y. miR-768-3p is involved in the proliferation, invasion and migration of non-small cell lung carcinomas. Int J Oncol. 2017;51(5):1574–82.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Changjiang Wang.

Ethics declarations

Conflict of interest

The authors have declared no conflict of interest.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cao, C., Wang, C. Clinical significance of serum miR-768-3p in HBV-related hepatocellular carcinoma and its potential mechanism. Clin Exp Med 20, 569–576 (2020). https://doi.org/10.1007/s10238-020-00646-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-020-00646-z

Keywords

Navigation