RETRACTED ARTICLE: Exosome circRNA secreted from adipocytes promotes the growth of hepatocellular carcinoma by targeting deubiquitination-related USP7

Oncogene - Tập 38 Số 15 - Trang 2844-2859 - 2019
Haiyang Zhang1, Ting Deng1, Shaohua Ge1, Ying Liu1, Ming Bai1, Kegan Zhu1, Qian Fan1, Jialu Li2,3, Tao Ning1, Fei Tian1, Hongli Li1, Wu Sun1, Guoguang Ying1, Yi Ba1
1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China
2Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease
3Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, 200001, China

Tóm tắt

AbstractHepatocellular carcinoma (HCC), the major form of liver cancer, has shown increasing incidence and poor prognosis. Adipose tissue is known to function in energy storage and metabolism regulation by the secretion of adipokines. Circular RNAs (circRNAs), a novel type of noncoding RNA, have recently been recognized as key factors in tumor development, but the role of exosome circRNAs derived from adipose tissues has not been defined yet. Here, adipose-secreted circRNAs were found to regulate deubiquitination in HCC, thus facilitating cell growth. It was observed that exosome circ-deubiquitination (circ-DB) is upregulated in HCC patients with higher body fat ratios. Moreover, in vitro and in vivo studies showed that exo-circ-DB promotes HCC growth and reduces DNA damage via the suppression of miR-34a and the activation of deubiquitination-related USP7. Finally, the results showed that the effects of adipose exosomes on HCC cells can be reversed by knockdown of circ-DB. These results indicate that exosome circRNAs secreted from adipocytes promote tumor growth and reduce DNA damage by suppressing miR-34a and activating the USP7/Cyclin A2 signaling pathway.

Từ khóa


Tài liệu tham khảo

Ziogas IA, Tsoulfas G. Advances and challenges in laparoscopic surgery in the management of hepatocellular carcinoma. World J Gastrointest Surg. 2017;9:233–45.

Axley P, Ahmed Z, Ravi S, Singal AK. Hepatitis C virus and hepatocellular carcinoma: a narrative review. J Clin Transl Hepatol. 2018;6:79–84.

Petruzziello A. Epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) related hepatocellular carcinoma. Open Virol J. 2018;12:26–32.

Aspichueta P. Lipid-rich environment: a key role promoting carcinogenesis in obesity-related non-alcoholic fatty liver disease. Gut. 2018;67:1376–7.

Gan L, Liu Z, Sun C. Obesity linking to hepatocellular carcinoma: a global view. Biochim Biophys Acta. 2018;1869:97–102.

Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569–79.

Yu B, Shao H, Su C, Jiang Y, Chen X, Bai L, et al. Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1. Sci Rep. 2016;6:34562.

Sun L, Xu R, Sun X, Duan Y, Han Y, Zhao Y, et al. Safety evaluation of exosomes derived from human umbilical cord mesenchymal stromal cell. Cytotherapy2016;18:413–22.

Cooks T, Pateras IS, Jenkins LM, Patel KM, Robles AI, Morris J, et al. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun. 2018;9:771.

Wilusz JE, Sharp PA. Molecular biology. A circuitous route to noncoding RNA. Science. 2013;340:440–1.

Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.

Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu JZ. et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19:141–57.

Li SS, Yao JP, Xie MJ, Liu YN, Zheng M. Exosomal miRNAs in hepatocellular carcinoma development and clinical responses. J Hematology Oncology 2018; 11: 54.

Cao CH, Sun JY, Zhang DY, Guo XJ, Xie LW, Li X, et al. The long intergenic noncoding RNA UFC1, a target of MicroRNA 34a, interacts with the mRNA stabilizing protein HuR to increase levels of beta-catenin in HCC cells. Gastroenterology. 2015;148:415–U249.

Coombs N, Sompallae R, Olbermann P, Gastaldello S, Goppel D, Masucci MG, et al. Helicobacter pylori affects the cellular deubiquitinase USP7 and ubiquitin-regulated components TRAF6 and the tumour suppressor p53. Int J Med Microbiol. 2011;301:213–24.

Zhang C, Lu J, Zhang QW, Zhao W, Guo JH, Liu SL, et al. USP7 promotes cell proliferation through the stabilization of Ki-67 protein in non-small cell lung cancer cells. Int J Biochem Cell Biol. 2016;79:209–21.

Novellasdemunt L, Foglizzo V, Cuadrado L, Antas P, Kucharska A, Encheva V, et al. USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating beta-catenin deubiquitination. Cell Rep. 2017;21:612–27.

Morra F, Merolla F, Napolitano V, Ilardi G, Miro C, Paladino S, et al. The combined effect of USP7 inhibitors and PARP inhibitors in hormone-sensitive and castration-resistant prostate cancer cells. Oncotarget. 2017;8:31815–29.

Carra G, Panuzzo C, Torti D, Parvis G, Crivellaro S, Familiari U, et al. Therapeutic inhibition of USP7-PTEN network in chronic lymphocytic leukemia: a strategy to overcome TP53 mutated/deleted clones. Oncotarget. 2017;8:35508–22.

Dong L, Yu L, Bai C, Liu L, Long H, Shi L, et al. USP27-mediated Cyclin E stabilization drives cell cycle progression and hepatocellular tumorigenesis. Oncogene. 2018;37:2702–13.

Wang Q, Ma S, Song N, Li X, Liu L, Yang S, et al. Stabilization of histone demethylase PHF8 by USP7 promotes breast carcinogenesis. J Clin Invest. 2016;126:2205–20.

Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.

Felicetti F, De Feo A, Coscia C, Puglisi R, Pedini F, Pasquini L, et al. Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma. J Transl Med. 2016;14:56.

Wei Y, Li MZ, Cui SF, Wang D, Zhang CY, Zen K et al. Shikonin inhibits the proliferation of human breast cancer cells by reducing tumor-derived exosomes. Molecules 2016; 21, 777.

Schmittgen TD, Lee EJ, Jiang JM, Sarkar A, Yang LQ, Elton TS, et al. Real-time PCR quantification of precursor and mature microRNA. Methods. 2008;44:31–38.

Chen CF, Ridzon DA, Broomer AJ, Zhou ZH, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33:e179.

Deng X, Zheng H, Li D, Xue Y, Wang Q, Yan S, et al. MicroRNA-34a regulates proliferation and apoptosis of gastric cancer cells by targeting silent information regulator 1. Exp Ther Med. 2018;15:3705–14.

Lv T, Song K, Zhang L, Li W, Chen Y, Diao Y, et al. MiRNA-34a decreases ovarian cancer cell proliferation and chemoresistance by targeting HDAC1. Biochem Cell Biol. 2018;96:663–71.

Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153–66.

Gopinathan L, Tan SL, Padmakumar VC, Coppola V, Tessarollo L, Kaldis P. Loss of Cdk2 and cyclin A2 impairs cell proliferation and tumorigenesis. Cancer Res. 2014;74:3870–9.

Palmer C, Corpuz T, Guirguis M, O’Toole S, Yan K, Bu Y, et al. The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection. Gut. 2010;59:397–404.

Hagstrom H, Tynelius P, Rasmussen F. High BMI in late adolescence predicts future severe liver disease and hepatocellular carcinoma: a national, population-based cohort study in 1.2 million men. Gut. 2017;67:1536–42.

Yin Y, Cai X, Chen X, Liang HW, Zhang YJ, Li J, et al. Tumor-secreted miR-214 induces regulatory T cells: a major link between immune evasion and tumor growth. Cell Res. 2014;24:1164–80.

Hannafon BN, Carpenter KJ, Berry WL, Janknecht R, Dooley WC, Ding WQ. Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA). Mol Cancer. 2015;14:133.

Zhang HY, Bai M, Deng T, Liu R, Wang X, Qu YJ, et al. Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma. Cancer Lett. 2016;375:331–9.

Farooqi AA, Desai NN, Qureshi MZ, Librelotto DRN, Gasparri ML, Bishayee A, et al. Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds. Biotechnol Adv. 2018;36:328–34.

Ji Q, Zhang CC, Sun XT, Li Q. Circular RNAs function as competing endogenous RNAs in multiple types of cancer. Oncol Lett. 2018;15:23–30.

Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO. Cell-type specific features of circular RNA expression. PLoS Genet. 2013;9:e1003777.

Colleran A, Collins PE, O’Carroll C, Ahmed A, Mao XC, McManus B, et al. Deubiquitination of NF-kappa B by Ubiquitin-Specific Protease-7 promotes transcription. Proc Natl Acad Sci USA. 2013;110:618–23.

Thông tin
Thông tin xuất bản

Oncogene

Tập 38 Số 15

2844-2859

Thông tin tác giả