BCL6B基因的生物学功能及其在肿瘤发生发展中作用的研究进展

doi:10.13481/j.1671-587X.20260229

Abstract

Abstract:

B-cell chronic lymphocytic leukemia/lymphoma 6 member B （BCL6B） gene is a homolog of B-cell/lymphoma 6 （BCL6） and belongs to the zinc finger and BTB domain-containing protein （ZBTB） family， playing an important role in regulating gene expression and cell proliferation. The function of BCL6B in various cellular processes and its potential clinical applications have attracted widespread attention. The BCL6B protein participates in the formation of transcriptional repression complexes and regulates multiple key signaling pathways including Notch and p53. In various solid tumors including hepatocellular carcinoma， gastric cancer， colorectal cancer， and breast cancer， BCL6B expression is frequently downregulated due to promoter hypermethylation， functioning as a tumor suppressor gene involved in inhibiting cell proliferation， migration， and invasion， and inducing apoptosis and cell cycle arrest； its high expression in a few tumors such as differentiated thyroid carcinoma also suggests the complexity of its function. Given the close association between BCL6B expression and tumor progression as well as patient prognosis， BCL6B is considered a promising prognostic biomarker and epigenetic therapeutic target. This article systematically reviewed the gene and protein structures and biological functions of BCL6B， with a focus on its role in the occurrence and development of various tumors and the latest research progress on the related molecular mechanisms， aiming to provide new insights for the precision diagnosis and treatment of tumors.

Key words: BCL6B gene, Gene function, Regulatory mechanism, Biomarker, Neoplasm

CLC Number:

R730.2

Yuqing PAN,Jiayan TAN,Suqin WANG,Ya LI. Research progress in biological function of BCL6B gene and its role in occurrence and development of tumor[J].Journal of Jilin University(Medicine Edition), 2026, 52(2): 551-560.

Figures/Tables 2

References 42

[1]	BRAY F， LAVERSANNE M， SUNG H， et al. Global cancer statistics 2022： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］. CA Cancer J Clin， 2024， 74（3）： 229-263.
[2]	XIA C F， DONG X S， LI H， et al. Cancer statistics in China and United States， 2022： profiles， trends， and determinants［J］. Chin Med J， 2022， 135（5）： 584-590.
[3]	SAKASHITA C， FUKUDA T， OKABE S， et al. Cloning and characterization of the human BAZF gene， a homologue of the BCL6 oncogene［J］. Biochem Biophys Res Commun， 2002， 291（3）： 567-573.
[4]	BARON B W， NUCIFORA G， MCCABE N， et al. Identification of the gene associated with the recurring chromosomal translocations t（3；14）（q27；q32） and t（3；22）（q27；q11） in B-cell lymphomas［J］. Proc Natl Acad Sci USA， 1993， 90（11）： 5262-5266.
[5]	YE B H， RAO P H， CHAGANTI R S， et al. Cloning of bcl-6， the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma［J］. Cancer Res， 1993， 53（12）： 2732-2735.
[6]	BARDWELL V J， TREISMAN R. The POZ domain： a conserved protein-protein interaction motif［J］. Genes Dev， 1994， 8（14）： 1664-1677.
[7]	OHNO H， FUKUHARA S. Significance of rearrangement of the BCL6 gene in B-cell lymphoid neoplasms［J］. Leuk Lymphoma， 1997， 27（1/2）： 53-63.
[8]	OKABE S， FUKUDA T， ISHIBASHI K， et al. BAZF， a novel Bcl6 homolog， functions as a transcriptional repressor［J］. Mol Cell Biol， 1998， 18（7）： 4235-4244.
[9]	TAKAMORI M， HATANO M， ARIMA M， et al. BAZF is required for activation of naive CD4 T cells by TCR triggering［J］. Int Immunol， 2004， 16（10）： 1439-1449.
[10]	LI Z H， WU W， LI Q S， et al. BCL6B-dependent suppression of ETV2 hampers endothelial cell differentiation［J］. Stem Cell Res Ther， 2024， 15（1）： 226.
[11]	ZHANG H， OKADA S， HATANO M， et al. A new functional domain of Bcl6 family that recruits histone deacetylases［J］. Biochim Biophys Acta， 2001， 1540（3）： 188-200.
[12]	XIANG T X， TANG J， LI L L， et al. Tumor suppressive BTB/POZ zinc-finger protein ZBTB28 inhibits oncogenic BCL6/ZBTB27 signaling to maintain p53 transcription in multiple carcinogenesis［J］. Theranostics， 2019， 9（26）： 8182-8195.
[13]	ZHU C， CHEN G， ZHAO Y， et al. Regulation of the development and function of B cells by ZBTB transcription factors［J］. Front Immunol， 2018， 9： 580.
[14]	OHNUKI H， INOUE H， TAKEMORI N， et al. BAZF， a novel component of cullin3-based E3 ligase complex， mediates VEGFR and Notch cross-signaling in angiogenesis［J］. Blood， 2012， 119（11）： 2688-2698.
[15]	MELNICK A， AHMAD K F， ARAI S， et al. In-depth mutational analysis of the promyelocytic leukemia zinc finger BTB/POZ domain reveals motifs and residues required for biological and transcriptional functions［J］. Mol Cell Biol， 2000， 20（17）： 6550-6567.
[16]	HARTATIK T， OKADA S， OKABE S， et al. Binding of BAZF and Bc16 to STAT6-binding DNA sequences［J］. Biochem Biophys Res Commun， 2001， 284（1）： 26-32.
[17]	TAKENAGA M， HATANO M， TAKAMORI M， et al. Bcl6-dependent transcriptional repression by BAZF［J］. Biochem Biophys Res Commun， 2003， 303（2）： 600-608.
[18]	黄鹏飞. BCL6B基因在抑制肝细胞肝癌和肝纤维化的发生发展的机制研究［D］. 杭州：浙江大学， 2016.
[19]	FITZGIBBON J， NEAT M J， JONES L， et al. Assignment of B-cell lymphoma 6， member B （zinc finger protein） gene （BCL6B） to human chromosome 17p13.1 by in situ hybridization［J］. Cytogenet Genome Res， 2000， 89（3）： 218-219.
[20]	XU L X， LI X X， CHU E S H， et al. Epigenetic inactivation of BCL6B， a novel functional tumour suppressor for gastric cancer， is associated with poor survival［J］. Gut， 2012， 61（7）： 977-985.
[21]	YANG Q F， GAO J， XU L X， et al. Promoter hypermethylation of BCL6B gene is a potential plasma DNA biomarker for gastric cancer［J］. Biomarkers， 2013， 18（8）： 721-725.
[22]	DENG J Y， LIANG H， DONG Q P， et al. The survival decrease in gastric cancer is associated with the methylation of B-cell CLL/lymphoma 6 member B promoter［J］. Open Biol， 2014， 4（7）： 140067.
[23]	马飞. TET1表观修饰BCL6B调控胃癌进展的机制［D］. 福州：福建医科大学， 2016.
[24]	CAI W Y， LIN L Y， WANG L， et al. Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice［J］. Cell Commun Signal， 2019， 17（1）： 72.
[25]	WANG J， DONG L， XU L X， et al. B cell CLL/lymphoma 6 member B inhibits hepatocellular carcinoma metastases in vitro and in mice［J］. Cancer Lett， 2014， 355（2）： 192-200.
[26]	WANG W L， HUANG P F， WU P， et al. BCL6B expression in hepatocellular carcinoma and its efficacy in the inhibition of liver damage and fibrogenesis［J］. Oncotarget， 2015， 6（24）： 20252-20265.
[27]	LI X， YU J， BROCK M V， et al. Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU［J］. Oncotarget， 2015， 6（13）： 11547-11560.
[28]	HU S， CAO B P， ZHANG M Y， et al. Epigenetic silencing BCL6B induced colorectal cancer proliferation and metastasis by inhibiting P53 signaling［J］. Am J Cancer Res， 2015， 5（2）： 651-662.
[29]	李爽，杨继元. BCL6B基因启动子区域甲基化与结肠癌的关系［J］. 中国临床研究， 2017， 30（6）： 729-731.
[30]	赵勇，章必成，高建飞，等. BCL6B基因启动子区域甲基化与结肠癌的关系研究［J］. 中国临床研究， 2016， 29（8）： 1013-1016， 1021.
[31]	白雪，杜井峰. 结肠癌患者BCL6B基因启动子区域甲基化检测结果分析［J］. 中外医疗， 2021， 40（22）： 185-187， 198.
[32]	谷月，李爱芳，孙晖，等. BCL6B对人结直肠癌LoVo细胞增殖和迁移的影响及机制［J］. 中国病理生理杂志， 2017， 33（1）： 38-45.
[33]	谷月，李爱芳，赵佳丽，等. BCL6B抑制结直肠癌细胞HCT116增殖、迁移及其可能机制研究［J］. 重庆医科大学学报， 2018， 43（1）： 36-41.
[34]	GU Y， LI A F， SUN H， et al. BCL6B suppresses proliferation and migration of colorectal carcinoma cells through inhibition of the PI3K/AKT signaling pathway［J］. Int J Mol Med， 2018， 41（5）： 2660-2668.
[35]	KRØIGÅRD A B， LARSEN M J， BRASCH-ANDERSEN C， et al. Genomic analyses of breast cancer progression reveal distinct routes of metastasis emergence［J］. Sci Rep， 2017， 7： 43813.
[36]	HE J， WU M J， XIONG L， et al. BTB/POZ zinc finger protein ZBTB16 inhibits breast cancer proliferation and metastasis through upregulating ZBTB28 and antagonizing BCL6/ZBTB27［J］. Clin Epigenetics， 2020， 12（1）： 82.
[37]	LI L， GONG Y J， TANG J， et al. ZBTB28 inhibits breast cancer by activating IFNAR and dual blocking CD24 and CD47 to enhance macrophages phagocytosis［J］. Cell Mol Life Sci， 2022， 79（2）： 83.
[38]	WANG J， DUAN Y， MENG Q H， et al. Integrated analysis of DNA methylation profiling and gene expression profiling identifies novel markers in lung cancer in Xuanwei， China［J］. PLoS One， 2018， 13（10）： e0203155.
[39]	LI L， GONG Y J， XU K， et al. ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis［J］. J Exp Clin Cancer Res， 2021， 40（1）： 150.
[40]	TONG X， XU L， RONG R， et al. Epigenetic silencing of ZBTB28 promotes renal cell carcinogenesis［J］. Asia Pac J Clin Oncol， 2022， 18（2）： e79-e86.
[41]	ZHAO L T， XIE H Y， LI P， et al. CircTFF1 promotes proliferation， migration and invasion of lung cancer cells by facilitating methylation of BCL6B promoter via miR-29c-3p/DNMT3A axis［J］. Mol Biotechnol， 2023， 65（6）： 942-952.
[42]	郑紫君. ZBTB蛋白家族在分化型甲状腺癌中的表达及预后研究［D］. 长春：吉林大学， 2023.

Research progress in biological function of BCL6B gene and its role in occurrence and development of tumor

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