Linc01559 Served as a Potential Oncogene and Promoted Resistance of Hepatocellular Carcinoma to Oxaliplatin by Directly Sponging miR-6783-3p

Author(s): Shunbin Dong, Ying Fu, Kaibo Yang, Xing Zhang, Runchen Miao, Yunxiang Long, Chang Liu*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 21 , Issue 2 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Oxaliplatin (L-OHP)-based chemotherapy, such as FOLFOX4 (5-fluorouracil, leucovorin, and L-OHP), improves the prognosis of patients with late-stage Hepatocellular Carcinoma (HCC). However, the development of resistance to L-OHP leads to the failure of chemotherapy. The aim of this study was to investigate the role of linc01559 and miR-6783-3p in regulating resistance to L-OHP.

Methods: Quantitative reverse transcription-polymerase chain reaction was used to determine the expression profile. The Cell Counting Kit-8 test and wound healing assay were also used. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation were used to evaluate the interaction between linc01559 and miR-6783-3p.

Result: linc01559 expression was associated with response to FOLFOX4, as well as miR-1343-3p and miR- 6783-3p expression in vivo. A nomogram, including linc01559 and miR-1343-3p, precisely and accurately predicted the overall survival of patients with HCC. Regarding the in vitro tests, linc01559 showed higher expression in L-OHP-resistant cell lines, whereas miR-6783-3p was downregulated. Knockdown of linc01559 led to decreased proliferation and migration ability, and increased expression of miR-6783-3p; however, it did not influence the expression of miR-1343-3p. We also found that linc01559 directly interacted with miR-6783-3p. Furthermore, linc01559 and miR-6783-3p regulated the viability of L-OHP-resistant cells following treatment with L-OHP.

Conclusion: linc01559 promoted the proliferation of HCC by sponging miR-6783-3p. This suggests that linc01559/miR-6783-3p may be key factors in regulating resistance and response to L-OHP. Moreover, they may be potential therapeutic targets for improving sensitivity to L-OHP in patients with HCC.

Keywords: Linc01559, miR-6783-3p, miR-1343-3p, oxaliplatin resistance, nomogram, hepatocellular carcinoma.

Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[] [PMID: 30207593]
Kamarajah, S.K.; Frankel, T.L.; Sonnenday, C.; Cho, C.S.; Nathan, H. Critical evaluation of the American Joint Commission on Cancer (AJCC) 8th edition staging system for patients with Hepatocellular Carcinoma (HCC): A Surveillance, Epidemiology, End Results (SEER) analysis In: J. Surg. Oncol; , 2018; 117, pp. (4)644-650.
Massarweh, N.N.; El-Serag, H.B. Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Control, 2017, 24(3)1073274817729245
Della Corte, C.; Triolo, M.; Iavarone, M.; Sangiovanni, A. Early diagnosis of liver cancer: An appraisal of international recommendations and future perspectives. Liver Int., 2016, 36(2), 166-176.
Bruix, J.; Reig, M.; Sherman, M. Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology, 2016, 150(4), 835-853.
[] [PMID: 26795574]
Dhamija, S.; Diederichs, S. From junk to master regulators of invasion: lncRNA functions in migration, EMT and metastasis. Int. J. Cancer, 2016, 139(2), 269-280.
[] [PMID: 26875870]
Yang, L.; Wang, H.; Shen, Q.; Feng, L.; Jin, H. Long non-coding RNAs involved in autophagy regulation. Cell Death Dis., 2017, 8(10)e3073
[] [PMID: 28981093]
Ding, B.; Lou, W.; Xu, L.; Fan, W. Non-coding RNA in drug resistance of hepatocellular carcinoma. Biosci. Rep., 2018, 38(5)BSR20180915
[] [PMID: 30224380]
Abbastabar, M.; Sarfi, M.; Golestani, A.; Khalili, E. lncRNA involvement in hepatocellular carcinoma metastasis and prognosis. EXCLI J., 2018, 17, 900-913.
[PMID: 30564069]
Lou, C.; Zhao, J.; Gu, Y.; Li, Q.; Tang, S.; Wu, Y.; Tang, J.; Zhang, C.; Li, Z.; Zhang, Y. LINC01559 accelerates pancreatic cancer cell proliferation and migration through YAP-mediated pathway. J. Cell. Physiol., 2020, 235(4), 3928-3938.
[PMID: 31608998]
Li, J.H.; Liu, S.; Zhou, H.; Qu, L.H.; Yang, J.H. starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res., 2014, 42(Database issue), D92-D97.
[] [PMID: 24297251]
Yang, J.H.; Li, J.H.; Shao, P.; Zhou, H.; Chen, Y.Q.; Qu, L.H. starBase: a database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data. Nucleic Acids Res., 2011, 39(Database issue), D202-D209.
[] [PMID: 21037263]
Zhou, Y.; Huang, T.; Zhang, J.; Wong, C.C.; Zhang, B.; Dong, Y.; Wu, F.; Tong, J.H.M.; Wu, W.K.K.; Cheng, A.S.L.; Yu, J.; Kang, W.; To, K.F. TEAD1/4 exerts oncogenic role and is negatively regulated by miR-4269 in gastric tumorigenesis. Oncogene, 2017, 36(47), 6518-6530.
[] [PMID: 28759040]
Yao, Y.; Hua, Q.; Zhou, Y. CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783-3p/DKK1 axis and inactivating Wnt/β-catenin signaling pathway. Biochem. Biophys. Res. Commun., 2019, 508(1), 37-45.
[] [PMID: 30470570]
Qin, S.; Gong, X. Progression of systemic chemotherapy with oxaliplatin-containing regimens for advanced hepatocellular carcinoma in China. Hepat. Oncol., 2016, 3(1), 71-81.
[] [PMID: 30191027]
Zheng, Z.; Liang, W.; Wang, D.; Schroder, P.M.; Ju, W.; Wu, L.; Zheng, Z.; Shang, Y.; Guo, Z.; He, X. Adjuvant chemotherapy for patients with primary hepatocellular carcinoma: A meta-analysis. Int. J. Cancer, 2015, 136(6), E751-E759.
[] [PMID: 25208979]
Marrero, J.A.; Kulik, L.M.; Sirlin, C.B.; Zhu, A.X.; Finn, R.S.; Abecassis, M.M.; Roberts, L.R.; Heimbach, J.K. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology, 2018, 68(2), 723-750.
[] [PMID: 29624699]
Qin, S.; Cheng, Y.; Liang, J.; Shen, L.; Bai, Y.; Li, J.; Fan, J.; Liang, L.; Zhang, Y.; Wu, G.; Rau, K.M.; Yang, T.S.; Jian, Z.; Liang, H.; Sun, Y. Efficacy and safety of the FOLFOX4 regimen versus doxorubicin in Chinese patients with advanced hepatocellular carcinoma: A subgroup analysis of the EACH study. Oncologist, 2014, 19(11), 1169-1178.
[] [PMID: 25223462]
Liu, L.; Zheng, Y.H.; Han, L.; Qin, S.K. Efficacy and safety of the oxaliplatin-based chemotherapy in the treatment of advanced primary hepatocellular carcinoma: A meta-analysis of prospective studies. Medicine (Baltimore), 2016, 95(40)e4993
[] [PMID: 27749557]
Abdel-Rahman, O. Revisiting oxaliplatin-based regimens for advanced hepatocellular carcinoma. Curr. Oncol. Rep., 2014, 16(8), 394.
[] [PMID: 24867344]
Parasramka, M.A.; Maji, S.; Matsuda, A.; Yan, I.K.; Patel, T. Long non-coding RNAs as novel targets for therapy in hepatocellular carcinoma. Pharmacol. Ther., 2016, 161, 67-78.
[] [PMID: 27013343]
Huang, H.; Chen, J.; Ding, C.M.; Jin, X.; Jia, Z.M.; Peng, J. LncRNA NR2F1-AS1 regulates hepatocellular carcinoma oxaliplatin resistance by targeting ABCC1 via miR-363. J. Cell. Mol. Med., 2018, 22(6), 3238-3245.
[] [PMID: 29602203]
Chen, B.; Wang, C.; Zhang, J.; Zhou, Y.; Hu, W.; Guo, T. New insights into long noncoding RNAs and pseudogenes in prognosis of renal cell carcinoma. Cancer Cell Int., 2018, 18, 157.
[] [PMID: 30337839]
Kim, H.; Yang, J.M.; Jin, Y.; Jheon, S.; Kim, K.; Lee, C.T.; Chung, J.H.; Paik, J.H. MicroRNA expression profiles and clinicopathological implications in lung adenocarcinoma according to EGFR, KRAS, and ALK status. Oncotarget, 2017, 8(5), 8484-8498.
[] [PMID: 28035073]
Yuan, T.; Huang, X.; Woodcock, M.; Du, M.; Dittmar, R.; Wang, Y.; Tsai, S.; Kohli, M.; Boardman, L.; Patel, T.; Wang, L. Plasma extracellular RNA profiles in healthy and cancer patients. Sci. Rep., 2016, 6, 19413.
[] [PMID: 26786760]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 21 July, 2020
Page: [278 - 286]
Pages: 9
DOI: 10.2174/1871520620666200721122317
Price: $65

Article Metrics

PDF: 93