同源盒蛋白B9及其翻译后修饰在肿瘤发生发展中的作用

何俊铭 于淼 张宏权 战军

解剖学报 ›› 2025, Vol. 56 ›› Issue (1) : 50-57.

PDF(1684 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(1684 KB)
解剖学报 ›› 2025, Vol. 56 ›› Issue (1) : 50-57. DOI: 10.16098/j.issn.0529-1356.2025.01.007
肿瘤学专栏

同源盒蛋白B9及其翻译后修饰在肿瘤发生发展中的作用

  • 何俊铭1,2  于淼张宏权2* 战军2*
作者信息 +

Role of homeobox B9 and its post-translational modifications in the genesis and development of tumor

  • HE Jun-ming1,2  YU Miao2  ZHANG Hong-quan2*  ZHAN Jun2*
Author information +
文章历史 +

摘要

同源盒蛋白(HOX)基因编码了一组进化上高度保守的蛋白,且与胚胎的轴向发育密切相关,HOX基因的缺失或异常表达引起的体节发育异常已在果蝇及小鼠等动物中被观察到。而后续研究发现,HOX基因家族编码的蛋白质也参与肿瘤发生发展的调控。以往作者对HOX全家族进行了综述,随着研究的深入,我们关注到该家族成员HOXB9的重要作用,并在该蛋白翻译后修饰的研究中取得了新的进展。我们以HOXB9为主线,对该分子参与的肿瘤相关信号通路以及该分子翻译后修饰对肿瘤进展的调节作用进行了总结,并对未来可能的研究方向做出展望。



Abstract

Homeobox(HOX) genes encode a group of proteins that are highly conserved and closely related to the axial differentiation of embryos. The disorder of segmental development caused by HOX genes deficiency or abnormal expression has been observed in drosophila and mice. However, subsequent studies have found that proteins encoded by the HOX gene family are also involved in the regulation of tumor genesis and development. The roles of the whole HOX family had been reviewed by the author in the past, and through the in-depth researches, the author paid attention to the pivotal role of HOXB9 and made new progress in the study of post-translational modifications of this protein. Taking HOXB9 as a clue, this review summarizes the tumor-related signaling pathways and the modulating effects of post-translational modification of HOXB9 on tumor progression, as well as the possible research directions in the future.


关键词

同源盒蛋白B9 / 翻译后修饰 / 肿瘤

Key words

 Homeobox B9 / Post-translational modifications / Tumor

引用本文

导出引用
何俊铭 于淼 张宏权 战军. 同源盒蛋白B9及其翻译后修饰在肿瘤发生发展中的作用[J]. 解剖学报. 2025, 56(1): 50-57 https://doi.org/10.16098/j.issn.0529-1356.2025.01.007
HE Jun-ming YU Miao ZHANG Hong-quan ZHAN Jun. Role of homeobox B9 and its post-translational modifications in the genesis and development of tumor[J]. Acta Anatomica Sinica. 2025, 56(1): 50-57 https://doi.org/10.16098/j.issn.0529-1356.2025.01.007
中图分类号: R730.23   

参考文献

[1]Yu M, Zhan J, Zhang H. HOX family transcription factors: Related signaling pathways and post-translational modifications in cancer[J]. Cell Signal,2020,66:109469.
[2]Contarelli S, Fedele V, Melisi D. HOX genes family and cancer: a novel role for homeobox B9 in the resistance to anti-angiogenic therapies[J]. Cancers (Basel),2020,12(11):3299.
[3]Mcginnis W, Levine MS, Hafen E, et al. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes[J]. Nature,1984,308(5958):428-433.
[4]Horan GS, Ramírez-Solis R, Featherstone MS, et al. Compound mutants for the paralogous hoxa-4, hoxb-4, and hoxd-4 genes show more complete homeotic transformations and a dose-dependent increase in the number of vertebrae transformed[J]. Genes Dev,1995,9(13):1667-1677.
[5]Mcintyre DC, Rakshit S, Yallowitz AR, et al. Hox patterning of the vertebrate rib cage[J]. Development,2007,134(16):2981-2989.
[6]Garcia-Gasca A, Spyropoulos DD. Differential mammary morphogenesis along the anteroposterior axis in Hoxc6 gene targeted mice[J]. Dev Dyn,2000,219(2):261-276.
[7]van den Akker E, Fromental-Ramain C, de Graaff W, et al. Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes[J]. Development,2001,128(10):1911-1921.
[8]Chen F, Greer J, Capecchi MR. Analysis of Hoxa7/Hoxb7 mutants suggests periodicity in the generation of the different sets of vertebrae[J]. Mech Dev,1998,77(1):49-57.
[9]Mallo M. Reassessing the role of hox genes during vertebrate development and evolution[J]. Trends Genet,2018,34(3):209-217.
[10]Wellik DM, Capecchi MR. Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton[J]. Science,2003,301(5631):363-367.
[11]Carapu?o M, Nóvoa A, Bobola N, et al. Hox genes specify vertebral types in the presomitic mesoderm[J]. Genes Dev,2005,19(18):2116-2121.
[12]Wei XG, Bi KW, Li B. Phenotypic Plasticity conferred by the metastatic microenvironment of the brain strengthens the intracranial tumorigenicity of lung tumor cells[J]. Front Oncol,2021,11:637911.
[13]Bai L, Ge P, Zhang Y, et al. Homeobox B9 promotes the progression of hepatocellular carcinoma via TGF-β1/Smad and ERK1/2 signaling pathways[J]. Biomed Res Int,2022,2022:1080315.
[14]Zhang G, Fan E, Yue G, et al. Five genes as a novel signature for predicting the prognosis of patients with laryngeal cancer[J]. J Cell Biochem,2020,121(8-9):3804-3813.
[15]Yang X, Cheng Y, Li X, et al. A novel transcription factor-based prognostic signature in endometrial cancer: establishment and validation[J]. Onco Targets Ther,2021,14:2579-2598.
[16]Jones FS, Prediger EA, Bittner DA, et al. Cell adhesion molecules as targets for Hox genes: neural cell adhesion molecule promoter activity is modulated by cotransfection with Hox-2.5 and -2.4[J]. Proc Natl Acad Sci USA,1992,89(6):2086-2090.
[17]Zappavigna V, Renucci A, Izpisúa-Belmonte JC, et al. HOX4 genes encode transcription factors with potential auto- and cross-regulatory capacities[J]. EMBO J,1991,10(13):4177-4187.
[18]Nagel S, Burek C, Venturini L, et al. Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1[J]. Blood,2007,109(7):3015-3023.
[19]Lin J, Zhang D, Fan Y, et al. Regulation of cancer stem cell self-renewal by HOXB9 antagonizes endoplasmic reticulum stress-induced melanoma cell apoptosis via the miR-765-FOXA2 Axis[J]. J Invest Dermatol,2018,138(7):1609-1619.
[20]Xu H, Wu S, Shen X, et al. Silencing of HOXB9 suppresses cellular proliferation, angiogenesis, migration and invasion of prostate cancer cells[J]. J Biosci,2020,45:40.
[21]Wan J, Liu H, Feng Q, et al. HOXB9 promotes endometrial cancer progression by targeting E2F3[J]. Cell Death Dis,2018,9(5):509.
[22]Francis JC, Gardiner JR, Renaud Y, et al. HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours[J]. Br J Cancer,2021,124(4):805-816.
[23]Zheng H, Li C, Li Z, et al. HOXB9 enhances the ability of lung cancer cells to penetrate the blood-brain barrier[J]. Aging (Albany NY),2020,13(4):4999-5019.
[24]Hayashida T, Takahashi F, Chiba N, et al. HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis[J]. Proc Natl Acad Sci USA,2010,107(3):1100-1105.
[25]Zhang L, Wu Q, He C, et al. HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression[J]. Dig Liver Dis,2019,51(1):157-165.
[26]Zhan J, Niu M, Wang P, et al. Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients[J]. Br J Cancer,2014,111(5):883-893.
[27]Zhan J, Song J, Wang P, et al. Kindlin-2 induced by TGF-β signaling promotes pancreatic ductal adenocarcinoma progression through downregulation of transcriptional factor HOXB9[J]. Cancer Lett,2015,361(1):75-85.
[28]Yao Y, Liu C, Wang B, et al. HOXB9 blocks cell cycle progression to inhibit pancreatic cancer cell proliferation through the DNMT1/RBL2/c-Myc axis[J]. Cancer Lett,2022,533:215595.
[29]Nguyen DX, Chiang AC, Zhang XH, et al. WNT/TCF signaling through LEF1 and HOXB9 mediates lung adenocarcinoma metastasis[J]. Cell,2009,138(1):51-62.
[30]Yuan R, Wang K, Hu J, et al. Ubiquitin-like protein FAT10 promotes the invasion and metastasis of hepatocellular carcinoma by modifying β-catenin degradation[J]. Cancer Res,2014,74(18):5287-5300.
[31]Xiong H, Xiao H, Luo C, et al. GRP78 activates the Wnt/HOXB9 pathway to promote invasion and metastasis of hepatocellular carcinoma by chaperoning LRP6[J]. Exp Cell Res,2019,383(1):111493.
[32]Ansari KI, Shrestha B, Hussain I, et al. Histone methylases MLL1 and MLL3 coordinate with estrogen receptors in estrogen-mediated HOXB9 expression[J]. Biochemistry,2011,50(17):3517-3527.
[33]Schmidt V, Sieckmann T, Kirschner KM, et al. WT1 regulates HOXB9 gene expression in a bidirectional way[J]. Biochim Biophys Acta Gene Regul Mech,2021,1864(11-12):194764.
[34]Drabsch Y, Ten DP. TGF-β signalling and its role in cancer progression and metastasis[J]. Cancer Metastasis Rev,2012,31(3-4):553-568.
[35]Sha L, Dong L, Lv L, et al. HOXB9 promotes epithelial-to-mesenchymal transition via transforming growth factor-β1 pathway in hepatocellular carcinoma cells[J]. Clin Exp Med,2015,15(1):55-64.
[36]Xue M, Zhu FY, Chen L, et al. HoxB9 promotes the migration and invasion via TGF-β1/Smad2/Slug signaling pathway in oral squamous cell carcinoma[J]. Am J Transl Res,2017,9(3):1151-1161.
[37]Suh DH, Park WH, Kim M, et al. HOXB9 overexpression confers chemoresistance to ovarian cancer cells by inducing ERCC-1, MRP-2, and XIAP[J]. Int J Mol Sci,2023,24(2):1249.
[38]Guo Z, Li N, Jiang Y, et al. HOXB9 a miR-122-5p regulated gene, suppressed the anticancer effects of brassaol by upregulating SCD1 expression in melanoma[J]. Biomed Pharmacother,2023,162:114650.
[39]Wan J, Xu W, Zhan J, et al. PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6[J]. Nucleic Acids Res,2016,44(22):10662-10675.
[40]Song J, Wang T, Xu W, et al. HOXB9 acetylation at K27 is responsible for its suppression of colon cancer progression[J]. Cancer Lett,2018,426:63-72.
[41]Sun X, Song J, Zhang J, et al. Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal adenocarcinoma[J]. Front Med,2020,14(1):91-100.
[42]Wang T, Guo H, Li Q, et al. The AMPK-HOXB9-KRAS axis regulates lung adenocarcinoma growth in response to cellular energy alterations[J]. Cell Rep,2022,40(8):111210.
[43]Xia YC, Zha JH, Sang YH, et al. AMPK activation by ASP4132 inhibits non-small cell lung cancer cell growth[J]. Cell Death Dis,2021,12(4):365.
[44]Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression[J]. Nat Rev Cancer,2009,9(8):563-575.
[45]Gao Y, P?ivinen P, Tripathi S, et al. Inactivation of AMPK leads to attenuation of antigen presentation and immune evasion in lung adenocarcinoma[J]. Clin Cancer Res,2022,28(1):227-237.
[46]Cai Z, Li CF, Han F, et al. Phosphorylation of PDHA by AMPK drives TCA cycle to promote cancer metastasis[J]. Mol Cell,2020,80(2):263-278.
[47]Wu SY, Rupaimoole R, Shen F, et al. A miR-192-EGR1-HOXB9 regulatory network controls the angiogenic switch in cancer[J]. Nat Commun,2016,7:11169.
[48]Michalak EM, Burr ML, Bannister AJ, et al. The roles of DNA, RNA and histone methylation in ageing and cancer[J]. Nat Rev Mol Cell Biol,2019,20(10):573-589.
[49]Fang Y, Xu X, Ding J, et al. Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells[J]. Cell Stem Cell,2021,28(4):748-763.
[50]Yu J, Chai P, Xie M, et al. Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma[J]. Genome Biol,2021,22(1):85.

基金

国家自然科学基金面上项目;北京市自然科学基金面上项目

PDF(1684 KB)

Accesses

Citation

Detail

段落导航
相关文章

/