Downregulation of circular RNA circPVT1 restricts cell growth of hepatocellular carcinoma through downregulation of Sirtuin 7 via microRNA-3666.

Publisher: Wiley-Blackwell Country of Publication: Australia NLM ID: 0425076 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1681 (Electronic) Linking ISSN: 03051870 NLM ISO Abbreviation: Clin Exp Pharmacol Physiol

Publication: Oxford, England : Wiley-Blackwell
Original Publication: Oxford, Blackwell Scientific Publications.

MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Carcinoma, Hepatocellular*/genetics ; Carcinoma, Hepatocellular*/pathology ; Carcinoma, Hepatocellular*/metabolism ; Liver Neoplasms*/genetics ; Liver Neoplasms*/pathology ; Liver Neoplasms*/metabolism ; RNA, Circular*/genetics ; RNA, Circular*/metabolism ; Down-Regulation*/genetics ; Cell Proliferation*/genetics ; Sirtuins*/genetics ; Sirtuins*/metabolism ; Gene Expression Regulation, Neoplastic*; Humans ; Cell Line, Tumor ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Apoptosis/genetics

Circular RNAs (circRNAs) have been identified recently as pivotal regulators in the development and progression of cancers, generally by acting as competing endogenous RNAs of microRNAs (miRNAs) to regulate gene expression. The dysregulation of circRNAs in hepatocellular carcinoma (HCC) has attracted much attention, but the precise role of circRNAs in HCC remains largely unknown. In this study, we aimed to investigate the potential role of circular RNA PVT1 (circPVT1), a newly identified cancer-related circRNA, in HCC. Herein, we found that circPVT1 expression was significantly upregulated in HCC tissues and cell lines. Knockdown of circPVT1 significantly reduced the growth and colony formation, and increased cell apoptosis, of HCC cells. Our results further identified circPVT1 as a sponge for miR-3666. Knockdown of circPVT1 significantly increased miR-3666 expression in HCC cells. Moreover, miR-3666 expression was significantly downregulated in HCC tissues and was inversely correlated with circPVT1 expression. In addition, the overexpression of miR-3666 inhibited the growth of HCC cells by targeting Sirtuin 7 (SIRT7). Notably, miR-3666 inhibition or SIRT7 overexpression partially reversed the circPVT1 knockdown-mediated inhibitory effect on HCC cell growth. Overall, these results demonstrate that downregulation of circPVT1 represses HCC cell growth by upregulating miR-3666 to inhibit SIRT7, suggesting circPVT1 as a potential therapeutic target for HCC. Our study highlights the involvement of circPVT1/miR-3666/SIRT7 in regulating HCC cell growth.
(© 2020 John Wiley & Sons Australia, Ltd.)

Marquardt JU, Andersen JB, Thorgeirsson SS. Functional and genetic deconstruction of the cellular origin in liver cancer. Nat Rev Cancer. 2015;15(11):653-667.
Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095-2128.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, 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.
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.
Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380(15):1450-1462.
Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A. 1976;73(11):3852-3856.
Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19(2):141-157.
Hentze MW, Preiss T. Circular RNAs: splicing's enigma variations. Embo J. 2013;32(7):923-925.
Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 Is a circular RNA that can be translated and functions in myogenesis. Mol Cell. 2017;66(1):22-37.
Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384-388.
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333-338.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-233.
Verduci L, Strano S, Yarden Y, Blandino G. The circRNA-microRNA code: emerging implications for cancer diagnosis and treatment. Mol Oncol. 2019;13(4):669-680.
Kiran S, Anwar T, Kiran M, Ramakrishna G. Sirtuin 7 in cell proliferation, stress and disease: rise of the seventh Sirtuin! Cell Signal. 2015;27(3):673-682.
Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D, Sirri V. Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis. J Cell Sci. 2009;122(Pt 4):489-498.
Blank MF, Grummt I. The seven faces of SIRT7. Transcription. 2017;8(2):67-74.
Li H, Tian Z, Qu Y, et al. SIRT7 promotes thyroid tumorigenesis through phosphorylation and activation of Akt and p70S6K1 via DBC1/SIRT1 axis. Oncogene. 2019;38(3):345-359.
Chen KL, Li L, Yang FX, Li CM, Wang YR, Wang GL. SIRT7 depletion inhibits cell proliferation, migration, and increases drug sensitivity by activating p38MAPK in breast cancer cells. J Cell Physiol. 2018;233(9):6767-6778.
Haider R, Massa F, Kaminski L, et al. Sirtuin 7: a new marker of aggressiveness in prostate cancer. Oncotarget. 2017;8(44):77309-77316.
Tang M, Lu X, Zhang C, et al. Downregulation of SIRT7 by 5-fluorouracil induces radiosensitivity in human colorectal cancer. Theranostics. 2017;7(5):1346-1359.
Tang X, Shi L, Xie N, et al. SIRT7 antagonizes TGF-beta signaling and inhibits breast cancer metastasis. Nat Commun. 2017;8(1):017-00396.
Li W, Zhu D, Qin S. SIRT7 suppresses the epithelial-to-mesenchymal transition in oral squamous cell carcinoma metastasis by promoting SMAD4 deacetylation. J Exp Clin Cancer Res. 2018;37(1):018-0819.
Lee HS, Jung W, Lee E, et al. SIRT7, H3K18ac, and ELK4 immunohistochemical expression in hepatocellular carcinoma. J Pathol Transl Med. 2016;50(5):337-344.
Kim JK, Noh JH, Jung KH, et al. Sirtuin7 oncogenic potential in human hepatocellular carcinoma and its regulation by the tumor suppressors MiR-125a-5p and MiR-125b. Hepatology. 2013;57(3):1055-1067.
Panda AC, Grammatikakis I, Kim KM, et al. Identification of senescence-associated circular RNAs (SAC-RNAs) reveals senescence suppressor CircPVT1. Nucleic Acids Res. 2017;45(7):4021-4035.
Wang Z, Su M, Xiang B, Zhao K, Qin B. Circular RNA PVT1 promotes metastasis via miR-145 sponging in CRC. Biochem Biophys Res Commun. 2019;512(4):716-722.
Chen J, Li Y, Zheng Q, et al. Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer Lett. 2017;388:208-219.
Verduci L, Ferraiuolo M, Sacconi A, et al. The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex. Genome Biol. 2017;18(1):017-1368.
Hu J, Han Q, Gu Y, et al. Circular RNA PVT1 expression and its roles in acute lymphoblastic leukemia. Epigenomics. 2018;10(6):723-732.
Gaffo E, Boldrin E, Dal Molin A, et al. Circular RNA differential expression in blood cell populations and exploration of circRNA deregulation in pediatric acute lymphoblastic leukemia. Sci Rep. 2019;9(1):14670.
Zhu Y, Liu Y, Xiao B, et al. The circular RNA PVT1/miR-203/HOXD3 pathway promotes the progression of human hepatocellular carcinoma. Biol Open. 2019;8(9):bio043687.
Qin S, Zhao Y, Lim G, Lin H, Zhang X. Circular RNA PVT1 acts as a competing endogenous RNA for miR-497 in promoting non-small cell lung cancer progression. Biomed Pharmacother. 2019;111:244-250.
La A, Tolomeo D, Cifola I, et al. MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences. Leukemia. 2018;32(10):2152-2166.
Kun-Peng Z, Xiao-Long M, 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. 2018;14(3):321-330.
Pan L, Tang Z, Tang R. MicroRNA-3666 inhibits lung cancer cell proliferation, migration, and invasiveness by targeting BPTF. Biochem Cell Biol. 2018;27:1-8.
Wang G, Cai C, Chen L. MicroRNA-3666 regulates thyroid carcinoma cell proliferation via MET. Cell Physiol Biochem. 2016;38(3):1030-1039.
Liu W, Song Y, Zhang C, Gao P, Huang B, Yang J. The protective role of all-transretinoic acid (ATRA) against colorectal cancer development is achieved via increasing miR-3666 expression and decreasing E2F7 expression. Biomed Pharmacother. 2018;104:94-101.
Li D, Li L. MicroRNA3666 inhibits breast cancer cell proliferation by targeting sirtuin 7. Mol Med Rep. 2017;16(6):8493-8500.
Shi H, Ji Y, Zhang D, Liu Y, Fang P. MicroRNA-3666-induced suppression of SIRT7 inhibits the growth of non-small cell lung cancer cells. Oncol Rep. 2016;36(5):3051-3057.
Nahalkova J. Novel protein-protein interactions of TPPII, p53, and SIRT7. Mol Cell Biochem. 2015;409(1-2):13-22.
Lv J, Tian J, Zheng G, Zhao J. Sirtuin7 is involved in protecting neurons against oxygen-glucose deprivation and reoxygenation-induced injury through regulation of the p53 signaling pathway. J Biochem Mol Toxicol. 2017;31(10):1-8.
Kiran S, Oddi V, Ramakrishna G. Sirtuin 7 promotes cellular survival following genomic stress by attenuation of DNA damage, SAPK activation and p53 response. Exp Cell Res. 2015;331(1):123-141.
Zhao J, Wozniak A, Adams A, et al. SIRT7 regulates hepatocellular carcinoma response to therapy by altering the p53-dependent cell death pathway. J Exp Clin Cancer Res. 2019;38(1):252.
Hua S, Quan Y, Zhan M, Liao H, Li Y, Lu L. miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1. Cancer Cell Int. 2019;19:203.
Song S, Yang Y, Liu M, et al. MiR-125b attenuates human hepatocellular carcinoma malignancy through targeting SIRT6. Am J Cancer Res. 2018;8(6):993-1007.
Duan X, Hu J, Wang Y, Gao J, Peng D, Xia L. MicroRNA-145: a promising biomarker for hepatocellular carcinoma (HCC). Gene. 2014;541(1):67-68.

Keywords: HCC; SIRT7; circPVT1; circRNA; miR-3666

0 (MicroRNAs)
0 (RNA, Circular)
EC 3.5.1.- (Sirtuins)
0 (SIRT7 protein, human)
0 (MIRN3666 microRNA, human)
0 (PVT1 long-non-coding RNA, human)
0 (RNA, Long Noncoding)

Date Created: 20200205 Date Completed: 20240724 Latest Revision: 20240724

20240726

10.1111/1440-1681.13273

32017171