收稿日期: 2022-09-30
录用日期: 2022-12-10
网络出版日期: 2023-01-28
基金资助
国家自然科学基金(82000806);广东省基础与应用基础研究省企联合基金(2021A1515220118);广东省医学科研基金(A2020553);清远市科技计划项目(2018B036)
A review of RIZ1 regulation of the signal pathways in obesity and tumors
Received date: 2022-09-30
Accepted date: 2022-12-10
Online published: 2023-01-28
Supported by
National Natural Science Foundation of China(82000806);Guangdong Provincial Joint Fund for Basic and Applied Basic Research Foundation(2021A1515220118);Guangdong Medical Science and Technology Research Fund(2020553);Qingyuan Science & Technology Project(2018B036)
视网膜母细胞瘤结合锌指蛋白1（retinoblastoma-interacting zinc finger protein 1，RIZ1）基因，又称PRDM2（positive regulatory domain 2）基因，是PRDM基因家族一员，其蛋白序列包含1个PR结构域、1个核激素受体结合基序、8个锌指结构域和1个视网膜母细胞瘤蛋白（retinoblastoma protein，Rb）相互作用基序。RIZ1主要定位于细胞核内，在核内发挥转录抑制因子、基因调控、蛋白质-蛋白质相互作用等功能。RIZ1是代谢通路的重要参与者，其通过调控代谢相关基因影响基础代谢，抑制肥胖的形成；RIZ1功能突变或含量不足与多种肿瘤发生发展相关，其通过激活下游致癌基因或调控代谢参与肿瘤进程。RIZ1通过v-akt鼠科胸腺瘤病毒癌基因同源物Ⅲ（v-akt murine thymoma viral oncogene homolog 3，AKT3）、胰岛素样生长因子-1（insulin-like growth factor 1，IGF-1），以及作为协同激活剂等方式分别调控AKT/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）、IGF-1、雌激素这3条肿瘤和肥胖相关分子信号通路。3条分子通路功能有差异且其下游分子存在交叉，提示RIZ1在不同年龄、性别和器官中的作用可能不同。详细研究RIZ1与RIZ2在代谢进程中的调控作用有助于全面了解RIZ1参与肥胖和肿瘤形成的机制。未来基于RIZ1靶点进行诊断研究或功能恢复可能对代谢性疾病和肿瘤的诊断和治疗有重要意义。
谢小雷 , 江佩欣 , 张敬鸿 , 莫骏健 , 吴可凡 , 曾康逸 . 视网膜母细胞瘤结合锌指蛋白1调控肥胖和肿瘤信号通路研究综述[J]. 上海交通大学学报（医学版）, 2023 , 43(1) : 114 -119 . DOI: 10.3969/j.issn.1674-8115.2023.01.015
Retinoblastoma-interacting zinc finger protein 1 (RIZ1) gene, also known as positive regulatory domain 2 (PRDM2), is a member of the PRDM gene family whose protein sequence consists of a PR domain, a nuclear hormone receptor binding motif, eight zinc finger domains, and an Rb (retinoblastoma protein) interacting motif. RIZ1 is mainly localized in the nucleus, where it plays a role in transcriptional repressor, gene regulation, protein-protein interactions, and other functions. RIZ1 is an important participant in the metabolic pathway, which affects basal metabolism and inhibits the development of obesity by regulating metabolism-related genes; functional mutations or insufficient content of RIZ1 are associated with the development of a variety of tumors, which participate in tumor processes by activating downstream oncogenes or regulating metabolism. RIZ1 regulates three molecular signal pathways, AKT (v-akt murine thymoma viral oncogene homolog)/mTOR (mechanistic target of rapamycin kinase), IGF-1 (insulin-like growth factor 1), and estrogen, in tumors and obesity through AKT3 and IGF-1, respectively, or acting as a co-activator. The functional differences of the three molecular pathways and the crossover of their downstream molecules suggest that RIZ1 may function differently in different ages, genders, and organs. The study of the regulatory role of RIZ1 and RIZ2 in metabolic processes can help to fully understand the mechanism of RIZ1 involvement in obesity and tumor formation. In the future, diagnostic research or functional recovery based on RIZ1 targets may be of great significance for the diagnosis and treatment of metabolic diseases and tumor.
| 1 | BUYSE I M, SHAO G, HUANG S. The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein[J]. PNAS, 1995, 92(10): 4467-4471. |
| 2 | CASAMASSIMI A, RIENZO M, DI ZAZZO E, et al. Multifaceted role of PRDM proteins in human cancer[J]. Int J Mol Sci, 2020, 21(7): E2648. |
| 3 | TANADI C, BAMBANG A, WENDI I P, et al. The predictive value of PRDM2 in solid tumor: a systematic review and meta-analysis[J]. Peer J, 2020, 8: e8826. |
| 4 | XIE X, MAN X, ZHU Z, et al. Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway[J]. Obesity (Silver Spring), 2016, 24(2): 389-397. |
| 5 | LIU Q, QU X, XIE X, et al. Repression of Akt3 gene transcription by the tumor suppressor RIZ1[J]. Sci Rep, 2018, 8(1): 1528. |
| 6 | SCULLY T, ETTELA A, LEROITH D, et al. Obesity, type 2 diabetes, and cancer risk[J]. Front Oncol, 2020, 10: 615375. |
| 7 | DI TULLIO F, SCHWARZ M, ZORGATI H, et al. The duality of PRDM proteins: epigenetic and structural perspectives[J]. Febs J, 2022, 289(5): 1256-1275. |
| 8 | XIE M, SHAO G, BUYSE I M, et al. Transcriptional repression mediated by the PR domain zinc finger gene RIZ[J]. J Biol Chem, 1997, 272(42): 26360-26366. |
| 9 | SUN Y Z, STINE J M, ATWATER D Z, et al. Structural and functional characterization of the acidic region from the RIZ tumor suppressor[J]. Biochemistry, 2015, 54(6): 1390-1400. |
| 10 | HUANG S. Histone methyltransferases, diet nutrients and tumour suppressors[J]. Nat Rev Cancer, 2002, 2(6): 469-476. |
| 11 | CONGDON L M, SIMS J K, TUZON C T, et al. The PR-Set7 binding domain of Riz1 is required for the H4K20me1-H3K9me1 trans-tail 'histone code' and Riz1 tumor suppressor function[J]. Nucleic Acids Res, 2014, 42(6): 3580-3589. |
| 12 | CHEEDIPUDI S, PURI D, SALEH A, et al. A fine balance: epigenetic control of cellular quiescence by the tumor suppressor PRDM2/RIZ at a bivalent domain in the cyclin a gene[J]. Nucleic Acids Res, 2015, 43(13): 6236-6256. |
| 13 | CAI Z, ZOU Y, HU H, et al. RIZ1 negatively regulates ubiquitin-conjugating enzyme E2C/UbcH10 via targeting c-Myc in meningioma[J]. Am J Transl Res, 2017, 9(5): 2645-2655. |
| 14 | CARLING T, KIM K C, YANG X H et al. A histone methyltransferase is required for maximal response to female sex hormones[J]. Mol Cell Biol, 2004, 24(16): 7032-7042. |
| 15 | KHURANA S, KRUHLAK M J, KIM J, et al. A macrohistone variant links dynamic chromatin compaction to BRCA1-dependent genome maintenance[J]. Cell Rep, 2014, 8(4): 1049-1062. |
| 16 | RIENZO M, SORRENTINO A, DI ZAZZO E, et al. Searching for a putative mechanism of RIZ2 tumor-promoting function in cancer models[J]. Front Oncol, 2020, 10: 583533. |
| 17 | ZHOU W, ALONSO S, TAKAI D, et al. Requirement of RIZ1 for cancer prevention by methyl-balanced diet[J]. PLoS One, 2008, 3(10): e3390. |
| 18 | PASTURAL E, TAKAHASHI N, DONG W F, et al. RIZ1 repression is associated with insulin-like growth factor-1 signaling activation in chronic myeloid leukemia cell lines[J]. Oncogene, 2007, 26(11): 1586-1594. |
| 19 | BARBIER E, JOHNSTONE A L, KHOMTCHOUK B B, et al. Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2[J]. Mol Psychiatry, 2017, 22(12): 1746-1758. |
| 20 | The Lancet Diabetes Endocrinology. Childhood obesity: a growing pandemic[J]. Lancet Diabetes Endocrinol, 2022, 10(1): 1. |
| 21 | LUO Q, DU R, LIU W, et al. PI3K/Akt/mTOR signaling pathway: role in esophageal squamous cell carcinoma, regulatory mechanisms and opportunities for targeted therapy[J]. Front Oncol, 2022, 12: 852383. |
| 22 | DING L, ZHANG L, BISWAS S, et al. Akt3 inhibits adipogenesis and protects from diet-induced obesity via WNK1/SGK1 signaling[J]. JCI Insight, 2017, 2(22): 95687. |
| 23 | CORUM D G, JENKINS D P, HESLOP J A, et al. PDE5 inhibition rescues mitochondrial dysfunction and angiogenic responses induced by Akt3 inhibition by promotion of PRC expression[J]. J Biol Chem, 2020, 295(52): 18091-18104. |
| 24 | NADERI A. Genomic and epigenetic aberrations of chromosome 1p36.13 have prognostic implications in malignancies[J]. Chromosome Res, 2020, 28(3/4): 307-330. |
| 25 | YANG S, LIU T, CHENG H, et al. Decreased expression of retinoblastoma protein-interacting zinc-finger gene 1 is correlated with poor survival and aggressiveness of cervical cancer patients[J]. Front Oncol, 2019, 9: 1396. |
| 26 | PIAO Z, FANG W, MALKHOSYAN S, et al. Frequent frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability[J]. Cancer Res, 2000, 60(17): 4701-4704. |
| 27 | STEELE-PERKINS G, FANG W, YANG X H, et al. Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily[J]. Genes Dev, 2001, 15(17): 2250-2262. |
| 28 | GURU S A, SUMI M P, MIR R, et al. Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival[J]. BMC Cancer, 2022, 22(1): 405. |
| 29 | SHEN L, TOYOTA M, KONDO Y, et al. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer[J]. PNAS, 2007, 104(47): 18654-18659. |
| 30 | SORRENTINO A, FEDERICO A, RIENZO M, et al. PR/SET domain family and cancer: novel insights from the cancer genome atlas[J]. Int J Mol Sci, 2018, 19(10): E3250. |
| 31 | PANDZIC T, RENDO V, LIM J, et al. Somatic PRDM2 c.4467delA mutations in colorectal cancers control histone methylation and tumor growth[J]. Oncotarget, 2017, 8(58): 98646-98659. |
| 32 | MARUVKA Y E, MOUW K W, KARLIC R, et al. Analysis of somatic microsatellite indels identifies driver events in human tumors[J]. Nat Biotechnol, 2017, 35(10): 951-959. |
| 33 | BARRERO M J, CEJAS P, LONG H W, et al. Nutritional epigenetics in cancer[J]. Adv Nutr, 2022, 13(5): 1748-1761. |
| 34 | ROSSI V, STAIBANO S, ABBONDANZA C, et al. Expression of RIZ1 protein (retinoblastoma-interacting zinc-finger protein 1) in prostate cancer epithelial cells changes with cancer grade progression and is modulated in vitro by DHT and E2[J]. J Cell Physiol, 2009, 221(3): 771-777. |
| 35 | KOLB R, SUTTERWALA F S, ZHANG W. Obesity and cancer: inflammation bridges the two[J]. Curr Opin Pharmacol, 2016, 29: 77-89. |
| 36 | AVGERINOS K I, SPYROU N, MANTZOROS C S, et al. Obesity and cancer risk: emerging biological mechanisms and perspectives[J]. Metabolism, 2019, 92: 121-135. |
| 37 | KEY T J, BRADBURY K E, PEREZ-CORNAGO A, et al. Diet, nutrition, and cancer risk: what do we know and what is the way forward?[J]. BMJ, 2020, 368: m511. |
| 38 | LAKSHMIKUTTYAMMA A, PASTURAL E, TAKAHASHI N, et al. Bcr-Abl induces autocrine IGF-1 signaling[J]. Oncogene, 2008, 27(27): 3831-3844. |
| 39 | ABBONDANZA C, MEDICI N, NIGRO V, et al. The retinoblastoma-interacting zinc-finger protein RIZ is a downstream effector of estrogen action[J]. Proc Natl Acad Sci U S A, 2000, 97(7): 3130-3135. |
| 40 | GAZZERRO P, ABBONDANZA C, D'ARCANGELO A, et al. Modulation of RIZ gene expression is associated to estradiol control of MCF-7 breast cancer cell proliferation[J]. Exp Cell Res, 2006, 312(3): 340-349. |
| 41 | YI J, ZHU J, WU J, et al. Oncogenic activation of PI3K-AKT-mTOR signaling suppresses ferroptosis via SREBP-mediated lipogenesis[J]. Proc Natl Acad Sci U S A, 2020, 117(49): 31189-31197. |
| 42 | SAIR A T, LIU R H. Molecular regulation of phenolic compounds on IGF-1 signaling cascade in breast cancer[J]. Food Funct, 2022, 13(6): 3170-3184. |
| 43 | RODRíGUEZ-VALENTíN R, TORRES-MEJíA G, MARTíNEZ-MATSUSHITA L, et al. Energy homeostasis genes modify the association between serum concentrations of IGF-1 and IGFBP-3 and breast cancer risk[J]. Sci Rep, 2022, 12(1): 1837. |
| 44 | OSTLUND T, ALOTAIBI F, KYEREMATENG J, et al. Triazole-estradiol analogs: a potential cancer therapeutic targeting ovarian and colorectal cancer[J]. Steroids, 2022, 177: 108950. |
| 45 | DU Y, CARLING T, FANG W, et al. Hypermethylation in human cancers of the RIZ1 tumor suppressor gene, a member of a histone/protein methyltransferase superfamily[J]. Cancer Res, 2001, 61(22): 8094-8099. |
| 46 | ABBONDANZA C, DE ROSA C, D'ARCANGELO A, et al. Identification of a functional estrogen-responsive enhancer element in the promoter 2 of PRDM2 gene in breast cancer cell lines[J]. J Cell Physiol, 2012, 227(3): 964-975. |
| 47 | SAAVEDRA-PE?A R D M, TAYLOR N, RODEHEFFER M S. Insights of the role of estrogen in obesity from two models of ERα deletion[J]. J Mol Endocrinol, 2022, 68(4): 179-194. |
| 48 | DAI L, WEISS R B, DUNN D M, et al. Core transcriptional networks in Williams syndrome: IGF1-PI3K-AKT-mTOR, MAPK and actin signaling at the synapse echo autism[J]. Hum Mol Genet, 2021, 30(6): 411-429. |
| 49 | PRABAKARAN S, VITTER S, LUNDBERG G. Cardiovascular disease in women update: ischemia, diagnostic testing, and menopause hormone therapy[J]. Endocr Pract, 2022, 28(2): 199-203. |
| 50 | YAL?IN M, KA?AR M. Investigation of the hepatic mTOR/S6K1/SREBP1 signalling pathway in rats at different ages: from neonates to adults[J]. Mol Biol Rep, 2021, 48(11): 7415-7422. |
/
| 〈 |
|
〉 |