Skip to main content
Top
Published in: Clinical and Experimental Medicine 4/2020

01-11-2020 | Hepatitis B | Original Article

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

Authors: Chunyu Cao, Changjiang Wang

Published in: Clinical and Experimental Medicine | Issue 4/2020

Login to get access

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.
Literature
1.
go back to reference El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.CrossRef El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011;365(12):1118–27.CrossRef
2.
go back to reference 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.CrossRef 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.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference 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.CrossRef 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.CrossRef
5.
go back to reference 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.CrossRef 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.CrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
8.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference 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.CrossRef 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.CrossRef
10.
go back to reference 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.CrossRef 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.CrossRef
11.
go back to reference 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.PubMedPubMedCentral 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.PubMedPubMedCentral
12.
go back to reference 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.CrossRef 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.CrossRef
13.
go back to reference Wang G, Dong F, Xu Z, et al. MicroRNA profile in HBV-induced infection and hepatocellular carcinoma. BMC Cancer. 2017;17(1):805.CrossRef Wang G, Dong F, Xu Z, et al. MicroRNA profile in HBV-induced infection and hepatocellular carcinoma. BMC Cancer. 2017;17(1):805.CrossRef
14.
go back to reference 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.CrossRef 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.CrossRef
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference Hepatobiliary Surgery Group, CSoSCMA. Guidelines for surgical treatment of primary hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 2004;13(5):329–30. Hepatobiliary Surgery Group, CSoSCMA. Guidelines for surgical treatment of primary hepatocellular carcinoma. Zhonghua Gan Zang Bing Za Zhi. 2004;13(5):329–30.
17.
go back to reference Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRef Llovet JM, Bru C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329–38.CrossRef
18.
go back to reference 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.CrossRef 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.CrossRef
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRef 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.CrossRef
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRef Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.CrossRef
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference 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.CrossRef 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.CrossRef
26.
go back to reference 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.CrossRef 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.CrossRef
28.
go back to reference 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.CrossRef 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.CrossRef
29.
go back to reference 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.CrossRef 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.CrossRef
30.
go back to reference 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.CrossRef 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.CrossRef
31.
go back to reference 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.CrossRef 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.CrossRef
32.
go back to reference 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.CrossRef 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.CrossRef
33.
go back to reference 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.CrossRef 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.CrossRef
34.
go back to reference 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.CrossRef 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.CrossRef
35.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Clinical significance of serum miR-768-3p in HBV-related hepatocellular carcinoma and its potential mechanism
Authors
Chunyu Cao
Changjiang Wang
Publication date
01-11-2020
Publisher
Springer International Publishing
Published in
Clinical and Experimental Medicine / Issue 4/2020
Print ISSN: 1591-8890
Electronic ISSN: 1591-9528
DOI
https://doi.org/10.1007/s10238-020-00646-z

Other articles of this Issue 4/2020

Clinical and Experimental Medicine 4/2020 Go to the issue