Interference with circRNA DOCK1 inhibits hepatocellular carcinoma cell proliferation, invasion and migration by regulating the miR-654-5p/SMAD2 axis

Lu,Yujuan; Zhang,Jingzhi; Wu,Yanhui

doi:10.3892/mmr.2021.12247

Interference with circRNA DOCK1 inhibits hepatocellular carcinoma cell proliferation, invasion and migration by regulating the miR-654-5p/SMAD2 axis

Authors:
- Yujuan Lu
- Jingzhi Zhang
- Yanhui Wu
View Affiliations

Affiliations: Department of Infectious Diseases, Zibo Central Hospital, Zibo, Shandong 255036, P.R. China, Department of Critical Care Medicine, Zibo Integrated Chinese and Western Medicine Hospital, Zibo, Shandong 255026, P.R. China, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: June 25, 2021 https://doi.org/10.3892/mmr.2021.12247
Article Number: 609
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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 the fourth most common cause of cancer‑related death worldwide. The aim of the present study was to discuss the role of circular RNA (circRNA) dedicator of cytokinesis 1 (DOCK1) in HCC and whether it can affect cell proliferation, invasion and migration by regulating the microRNA (miR)‑654‑5p/SMAD2 axis. The expression levels of circRNA DOCK1, miR‑654‑5p and SMAD2 mRNA in HCC cells and transfected Hep3b cells were detected by reverse transcription‑quantitative PCR analysis. SMAD2 protein expression levels in HCC cells and transfected Hep3b cells were analyzed by western blot analysis. The viability, proliferation, migration and invasion of transfected Hep3b cells was in turn detected by Cell Counting Kit‑8, clone formation, wound healing and Transwell assays. The interaction of circRNA DOCK1 and miR‑654‑5p, miR‑654‑5p and SMAD2 was confirmed by the dual‑luciferase reporter assay. As a result, the expression of circRNA DOCK1 and SMAD2 was increased, and miR‑654‑5p was decreased in HCC cells. circRNA DOCK1 directly targeted to miR‑654‑5p and miR‑654‑5p directly targeted to SMAD2. Interference with circRNA DOCK1 inhibited the proliferation, invasion and migration of HCC cells by upregulating miR‑654‑5p expression. The effects of circRNA DOCK1 knockdown could be partially reversed by transfection with a miR‑654‑5p inhibitor and SMAD2 overexpression. In conclusion, interference with circRNA DOCK1 inhibited proliferation, invasion and migration of HCC cells by regulating the miR‑654‑5p/SMAD2 axis.

View Figures

View References

1	Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A and Roberts LR: A global view of hepatocellular carcinoma: Trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 16:589–604. 2019. View Article : Google Scholar : PubMed/NCBI
2	Llovet JM, Zucman-Rossi J, Pikarsky E, Sangro B, Schwartz M, Sherman M and Gores G: Hepatocellular carcinoma. Nat Rev Dis Primers. 2:160182016. View Article : Google Scholar : PubMed/NCBI
3	Roayaie S, Jibara G, Tabrizian P, Park JW, Yang J, Yan L, Schwartz M, Han G, Izzo F, Chen M, et al: The role of hepatic resection in the treatment of hepatocellular cancer. Hepatology. 62:440–451. 2015. View Article : Google Scholar : PubMed/NCBI
4	Kulik L and El-Serag HB: Epidemiology and management of hepatocellular carcinoma. Gastroenterology. 156:477–491.e1. 2019. View Article : Google Scholar : PubMed/NCBI
5	Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, Schirmacher P and Vilgrain V; European Association for the Study of the Liver. Electronic address, : easloffice@easloffice.eu; European Association for the Study of the Liver: EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 69:182–236. 2018. View Article : Google Scholar : PubMed/NCBI
6	Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, et al: Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: The EVOLVE-1 randomized clinical trial. JAMA. 312:57–67. 2014. View Article : Google Scholar : PubMed/NCBI
7	Lopez PM, Villanueva A and Llovet JM: Systematic review: Evidence-based management of hepatocellular carcinoma - an updated analysis of randomized controlled trials. Aliment Pharmacol Ther. 23:1535–1547. 2006. View Article : Google Scholar : PubMed/NCBI
8	Patop IL, Wüst S and Kadener S: Past, present, and future of circRNAs. EMBO J. 38:e1008362019. View Article : Google Scholar : PubMed/NCBI
9	Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF and Sharpless NE: Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 19:141–157. 2013. View Article : Google Scholar : PubMed/NCBI
10	Han TS, Hur K, Cho HS and Ban HS: Epigenetic associations between lncRNA/circRNA and miRNA in hepatocellular carcinoma. Cancers (Basel). 12:26222020. View Article : Google Scholar : PubMed/NCBI
11	Cui W and Xue J: Circular RNA DOCK1 downregulates microRNA-124 to induce the growth of human thyroid cancer cell lines. Biofactors. 46:591–599. 2020. View Article : Google Scholar : PubMed/NCBI
12	Liu P, Li X, Guo X, Chen J, Li C, Chen M, Liu L, Zhang X and Zu X: Circular RNA DOCK1 promotes bladder carcinoma progression via modulating circDOCK1/hsa-miR-132-3p/Sox5 signalling pathway. Cell Prolif. 52:e126142019. View Article : Google Scholar : PubMed/NCBI
13	Wang L, Wei Y, Yan Y, Wang H, Yang J, Zheng Z, Zha J, Bo P, Tang Y, Guo X, et al: CircDOCK1 suppresses cell apoptosis via inhibition of miR 196a 5p by targeting BIRC3 in OSCC. Oncol Rep. 39:951–966. 2018.PubMed/NCBI
14	Kong R: Circular RNA hsa_circ_0085131 is involved in cisplati-resistance of non-small-cell lung cancer cells by regulating autophagy. Cell Biol Int. 44:1945–1956. 2020. View Article : Google Scholar : PubMed/NCBI
15	Huang F, Wu X, Wei M, Guo H, Li H, Shao Z, Wu Y and Pu J: miR-654-5p Targets HAX-1 to regulate the nalignancy behaviors of colorectal cancer cells. BioMed Res Int. 2020:49147072020.PubMed/NCBI
16	Majem B, Parrilla A, Jiménez C, Suárez-Cabrera L, Barber M, Marín A, Castellví J, Tamayo G, Moreno-Bueno G, Ponce J, et al: MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways. Oncogene. 38:6035–6050. 2019. View Article : Google Scholar : PubMed/NCBI
17	Zhang JX, He WL, Feng ZH, Chen DL, Gao Y, He Y, Qin K, Zheng ZS, Chen C, Weng HW, et al: A positive feedback loop consisting of C12orf59/NF-κB/CDH11 promotes gastric cancer invasion and metastasis. J Exp Clin Cancer Res. 38:1642019. View Article : Google Scholar : PubMed/NCBI
18	Zheng S, Jia Q, Shen H, Xu X, Ling J, Jing C and Zhang B: Treatment with the herbal formula Songyou Yin inhibits epithelial-mesenchymal transition in hepatocellular carcinoma through downregulation of TGF-β1 expression and inhibition of the SMAD2/3 signaling pathway. Oncol Lett. 13:2309–2315. 2017. View Article : Google Scholar : PubMed/NCBI
19	Zheng X, Gai X, Han S, Moser CD, Hu C, Shire AM, Floyd RA and Roberts LR: The human sulfatase 2 inhibitor 2,4-disulfonylphenyl-tert-butylnitrone (OKN-007) has an antitumor effect in hepatocellular carcinoma mediated via suppression of TGFB1/SMAD2 and Hedgehog/GLI1 signaling. Genes Chromosomes Cancer. 52:225–236. 2013. View Article : Google Scholar : PubMed/NCBI
20	Wang J, Liu G, Li Q, Wang F, Xie F, Zhai R, Guo Y, Chen T, Zhang N, Ni W, et al: Mucin1 promotes the migration and invasion of hepatocellular carcinoma cells via JNK-mediated phosphorylation of Smad2 at the C-terminal and linker regions. Oncotarget. 6:19264–19278. 2015. View Article : Google Scholar : PubMed/NCBI
21	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. View Article : Google Scholar : PubMed/NCBI
22	Forner A, Reig M and Bruix J: Hepatocellular carcinoma. Lancet. 391:1301–1314. 2018. View Article : Google Scholar : PubMed/NCBI
23	Qin M, Liu G, Huo X, Tao X, Sun X, Ge Z, Yang J, Fan J, Liu L and Qin W: Hsa_circ_0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma. Cancer Biomark. 16:161–169. 2016. View Article : Google Scholar : PubMed/NCBI
24	Fu L, Wu S, Yao T, Chen Q, Xie Y, Ying S, Chen Z, Xiao B and Hu Y: Decreased expression of hsa_circ_0003570 in hepatocellular carcinoma and its clinical significance. J Clin Lab Anal. 32:e222392018. View Article : Google Scholar : PubMed/NCBI
25	Fu L, Chen Q, Yao T, Li T, Ying S, Hu Y and Guo J: Hsa_circ_0005986 inhibits carcinogenesis by acting as a miR-129-5p sponge and is used as a novel biomarker for hepatocellular carcinoma. Oncotarget. 8:43878–43888. 2017. View Article : Google Scholar : PubMed/NCBI
26	Liang WC, Wong CW, Liang PP, Shi M, Cao Y, Rao ST, Tsui SK, Waye MM, Zhang Q, Fu WM, et al: Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway. Genome Biol. 20:842019. View Article : Google Scholar : PubMed/NCBI
27	Xu XZ, Song H, Zhao Y and Zhang L: MiR-654-5p regulated cell progression and tumor growth through targeting SIRT6 in osteosarcoma. Eur Rev Med Pharmacol Sci. 24:3517–3525. 2020.PubMed/NCBI
28	Tan YY, Xu XY, Wang JF, Zhang CW and Zhang SC: MiR-654-5p attenuates breast cancer progression by targeting EPSTI1. Am J Cancer Res. 6:522–532. 2016.PubMed/NCBI
29	Li ZY, Wang XL, Dang Y, Zhu XZ, Zhang YH, Cai BX and Zheng L: Long non-coding RNA UCA1 promotes the progression of paclitaxel resistance in ovarian cancer by regulating the miR-654-5p/SIK2 axis. Eur Rev Med Pharmacol Sci. 24:591–603. 2020.PubMed/NCBI