Cisplatin resistance‑associated circRNA_101237 serves as a prognostic biomarker in hepatocellular carcinoma

Zhou,Shuping; Wei,Juan; Wang,Yeliu; Liu,Xinkuang

doi:10.3892/etm.2020.8526

Cisplatin resistance‑associated circRNA_101237 serves as a prognostic biomarker in hepatocellular carcinoma

Authors:
- Shuping Zhou
- Juan Wei
- Yeliu Wang
- Xinkuang Liu
View Affiliations

Affiliations: Department of Gastroenterology and Hepatology, Huainan First People's Hospital and First Affiliated Hospital of The Medical College of Anhui University of Science and Technology, Huainan, Anhui 232000, P.R. China, Department of Gastroenterology and Hepatology, Nanjing General Hospital, Nanjing, Jiangsu 210002, P.R. China
Published online on: February 12, 2020 https://doi.org/10.3892/etm.2020.8526
Pages: 2733-2740

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer‑associated mortality worldwide. Despite clinical advances, the survival rate of patients with HCC remains low, as most patients are diagnosed with HCC when they are already at the advanced stage. Certain circular RNAs (circRNAs) are closely associated with the development of liver cancer. In the present study, a circRNA array was performed to screen differentially expressed circRNAs in HCC tissues. The further analysis focused on the newly identified circRNA_101237, the host gene of which, cyclin‑dependent kinase 8, is located at chr13:26974589‑26975761. CircRNA_101237 was determined to be upregulated in tumor tissue and serum of patients with HCC as compared with that in paracancerous tissues and the serum of healthy controls, respectively. In addition, the expression of circRNA_101237 was associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. Univariate and multivariate analysis indicated that serum circRNA_101237 levels were an independent predictor of survival prognosis in patients with HCC. The overall survival of patients with high expression of circRNA_101237 was reduced compared with that of patients with low expression of circRNA_101237. Of note, cisplatin induced the expression of circRNA_101237 in HCC cells in a dose‑ and time‑dependent manner in vitro, and the levels of circRNA_101237 in the serum of patients with cisplatin‑resistant HCC and in cisplatin‑resistant Huh7 cells were increased. The present study provided novel insight into the use of circRNA_101237 as a diagnostic biomarker for HCC and a potential therapeutic target.

View Figures

View References

1	Sia D, Villanueva A, Friedman SL and Llovet JM: Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology. 152:745–761. 2017.PubMed/NCBI View Article : Google Scholar
2	Ikeda K: Recent advances in medical management of hepatocellular carcinoma. Hepatol Res. 49:14–32. 2019.PubMed/NCBI View Article : Google Scholar
3	Kawaoka T, Aikata H, Kobayashi T, Uchikawa S, Ohya K, Kodama K, Nishida Y, Daijo K, Osawa M, Teraoka Y, et al: Comparison of hepatic arterial infusion chemotherapy between 5-fluorouracil-based continuous infusion chemotherapy and low-dose cisplatin monotherapy for advanced hepatocellular carcinoma. Hepatol Res. 48:1118–1130. 2018.PubMed/NCBI View Article : Google Scholar
4	Shang X, Li G, Liu H, Li T, Liu J, Zhao Q and Wang C: Comprehensive circular RNA profiling reveals that hsa_circ_0005075, a new circular RNA biomarker, is involved in hepatocellular carcinoma development. Medicine (Baltimore). 95(e3811)2016.PubMed/NCBI View Article : Google Scholar
5	Sun X and Malhotra A: Noncoding RNAs (ncRNA) in hepato cancer: A review. J Environ Pathol Toxicol Oncol. 37:15–25. 2018.PubMed/NCBI View Article : Google Scholar
6	Lanzafame M, Bianco G, Terracciano LM, Ng C and Piscuoglio S: The role of long non-coding RNAs in hepatocarcinogenesis. Int J Mol Sci. 19(E682)2018.PubMed/NCBI View Article : Google Scholar
7	Qiu LP, Wu YH, Yu XF, Tang Q, Chen L and Chen KP: The emerging role of circular RNAs in hepatocellular carcinoma. J Cancer. 9:1548–1559. 2018.PubMed/NCBI View Article : Google Scholar
8	Liu BH, Zhang BB, Liu XQ, Zheng S, Dong KR and Dong R: Expression profiling identifies circular RNA signature in hepatoblastoma. Cell Physiol Biochem. 45:706–719. 2018.PubMed/NCBI View Article : Google Scholar
9	Wang M, Yang Y, Xu J, Bai W, Ren X and Wu H: CircRNAs as biomarkers of cancer: A meta-analysis. BMC Cancer. 18(303)2018.PubMed/NCBI View Article : Google Scholar
10	Zhu Q, Lu G, Luo Z, Gui F, Wu J, Zhang D and Ni Y: CircRNA circ_0067934 promotes tumor growth and metastasis in hepatocellular carcinoma through regulation of miR-1324/FZD5/Wnt/β-catenin axis. Biochem Biophys Res Commun. 497:626–632. 2018.PubMed/NCBI View Article : Google Scholar
11	Shi L, Yan P, Liang Y, Sun Y, Shen J, Zhou S, Lin H, Liang X and Cai X: Circular RNA expression is suppressed by androgen receptor (AR)-regulated adenosine deaminase that acts on RNA (ADAR1) in human hepatocellular carcinoma. Cell Death Dis. 8(e3171)2017.PubMed/NCBI View Article : Google Scholar
12	Zhang X, Qiu S, Luo P, Zhou H, Jing W, Liang C and Tu J: Down-regulation of hsa_circ_0001649 in hepatocellular carcinoma predicts a poor prognosis. Cancer Biomark. 22:135–142. 2018.PubMed/NCBI View Article : Google Scholar
13	Han D, Li J, Wang H, Su X, Hou J, Gu Y, Qian C, Lin Y, Liu X, Huang M, et al: Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 66:1151–1164. 2017.PubMed/NCBI View Article : Google Scholar
14	Shao YY, Liang PC, Wu YM, Huang CC, Huang KW, Cheng JC, Hsu CH, Hsu C, Cheng AL and Lin ZZ: A pilot study of hepatic arterial infusion of chemotherapy for patients with advanced hepatocellular carcinoma who have failed anti-angiogenic therapy. Liver Int. 33:1413–1419. 2013.PubMed/NCBI View Article : Google Scholar
15	Wakamatsu T, Nakahashi Y, Hachimine D, Seki T and Okazaki K: The combination of glycyrrhizin and lamivudine can reverse the cisplatin resistance in hepatocellular carcinoma cells through inhibition of multidrug resistance-associated proteins. Int J Oncol. 31:1465–1472. 2007.PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
17	Fu J and Wang H: Precision diagnosis and treatment of liver cancer in China. Cancer Lett. 412:283–288. 2018.PubMed/NCBI View Article : Google Scholar
18	Tsuchiya N, Sawada Y, Endo I, Saito K, Uemura Y and Nakatsura T: Biomarkers for the early diagnosis of hepatocellular carcinoma. World J Gastroenterol. 21:10573–10583. 2015.PubMed/NCBI View Article : Google Scholar
19	Amable L: Cisplatin resistance and opportunities for precision medicine. Pharmacol Res. 106:27–36. 2016.PubMed/NCBI View Article : Google Scholar
20	Hu Y, Zhu QN, Deng JL, Li ZX, Wang G and Zhu YS: Emerging role of long non-coding RNAs in cisplatin resistance. Onco Targets Ther. 11:3185–3194. 2018.PubMed/NCBI View Article : Google Scholar
21	Kataoka J, Shiraha H, Horiguchi S, Sawahara H, Uchida D, Nagahara T, Iwamuro M, Morimoto H, Takeuchi Y, Kuwaki K, et al: Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma. Oncol Rep. 35:2576–2582. 2016.PubMed/NCBI View Article : Google Scholar
22	Kim Y, Jang M, Lim S, Won H, Yoon KS, Park JH, Kim HJ, Kim BH, Park WS, Ha J and Kim SS: Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans. Hepatology. 54:1661–1678. 2011.PubMed/NCBI View Article : Google Scholar
23	Achkar IW, Abdulrahman N, Al-Sulaiti H, Joseph JM, Uddin S and Mraiche F: Cisplatin based therapy: The role of the mitogen activated protein kinase signaling pathway. J Transl Med. 16(96)2018.PubMed/NCBI View Article : Google Scholar
24	Xu N, Chen S, Liu Y, Li W, Liu Z, Bian X, Ling C and Jiang M: Profiles and bioinformatics analysis of differentially expressed Circrnas in taxol-resistant non-small cell lung cancer cells. Cell Physiol Biochem. 48:2046–2060. 2018.PubMed/NCBI View Article : Google Scholar
25	Ding B, Lou W, Xu L and Fan W: Non-coding RNA in drug resistance of hepatocellular carcinoma. Biosci Rep. 38(BSR20180915)2018.PubMed/NCBI View Article : Google Scholar
26	Shao F, Huang M, Meng F and Huang Q: Circular RNA signature predicts gemcitabine resistance of pancreatic ductal adenocarcinoma. Front Pharmacol. 9(584)2018.PubMed/NCBI View Article : Google Scholar
27	Kun-Peng Z, Xiao-Long M, Lei Z, Chun-Lin Z, Jian-Ping H and Tai-Cheng Z: Screening circular RNA related to chemotherapeutic resistance in osteosarcoma by RNA sequencing. Epigenomics. 10:1327–1346. 2018.PubMed/NCBI View Article : Google Scholar
28	Liu Y, Dong Y, Zhao L, Su L and Luo J: Circular RNAMTO1 suppresses breast cancer cell viability and reverses monastrol resistance through regulating the TRAF4/Eg5 axis. Int J Oncol. 53:1752–1762. 2018.PubMed/NCBI View Article : Google Scholar
29	Kun-Peng Z, Xiao-Long M and Chun-Lin Z: Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int J Biol Sci. 14:321–330. 2018.PubMed/NCBI View Article : Google Scholar