FUS and PTBP1 Cooperatively Promote Chronic Myeloid Leukemia Progression via Transcriptional and Post-transcriptional Regulation

doi:10.19586/j.2095-2341.2026.0010

Current Biotechnology ›› 2026, Vol. 16 ›› Issue (3): 677-685.DOI: 10.19586/j.2095-2341.2026.0010

• Articles • Previous Articles Next Articles

FUS and PTBP1 Cooperatively Promote Chronic Myeloid Leukemia Progression via Transcriptional and Post-transcriptional Regulation

Lexuan LIN¹(), Xu JIN¹, Fang HE¹(), Lihong SHI¹^,²()

^1.State Key Laboratory of Experimental Hematology，National Clinical Research Center for Blood Disease，Haihe Laboratory of Cell Ecosystem，Institute of Hematology Blood Diseases Hospital，Chinese Academy of Medical Sciences Peking Union Medical College，Tianjin 300020，China
^2.Tianjin Institutes of Health Science，Tianjin 301600，China

Received:2026-01-16 Accepted:2026-04-02 Online:2026-05-25 Published:2026-07-14
Contact: Fang HE,Lihong SHI

Abstract

Abstract:

The heterogeneous nuclear ribonucleoproteins （hnRNPs） family is involved in the development of various tumors， but its role in chronic myeloid leukemia （CML） remains unclear. Previous studies have confirmed that fused in sarcoma （FUS） is a key gene maintaining CML cell proliferation， and its high expression is associated with poor patient prognosis. The study integrated clustered regularly interspaced short palindromic repeats （CRISPR） screening， RNA interference， and cell function experiments to systematically verify the key role of FUS in CML. Knockdown of FUS significantly inhibited the proliferation of K562 cells， leading to quiescent phase （G0 phase） arrest and promoting apoptosis. Nuclear FUS binds to promoter regions and shows overlapping target genes with the transcriptional co-activator bromodomain protein 4 （BRD4） and the chromatin remodeler brahma-related gene 1 （BRG1）， suggesting potential collaborative regulation of chromatin structure and transcriptional activity. Additionally， FUS can interact with polypyrimidine tract binding protein 1 （PTBP1）， and the two may cooperatively regulate gene expression and post-transcriptional processing， jointly promoting CML cell survival. In summary， FUS may maintain oncogenic transcriptional programs by regulating chromatin spatial architecture and forms a functional cooperative network with PTBP1 at both transcriptional and post-transcriptional levels， collectively driving CML progression.

Key words: chronic myeloid leukemia, FUS, PTBP1

CLC Number:

Q291

Lexuan LIN, Xu JIN, Fang HE, Lihong SHI. FUS and PTBP1 Cooperatively Promote Chronic Myeloid Leukemia Progression via Transcriptional and Post-transcriptional Regulation[J]. Current Biotechnology, 2026, 16(3): 677-685.

Add to citation manager EndNote|Ris|BibTeX

URL: https://swjsjz.magtechjournal.com/EN/10.19586/j.2095-2341.2026.0010

https://swjsjz.magtechjournal.com/EN/Y2026/V16/I3/677

Figures/Tables 5

Table 1 shRNA sequences in this study

引物名称	shRNA序列（5'→3')	引物名称	shRNA序列（5'→3')
shFUS-1	5'-GGACAGCAGCAAAGCTATA-3'	shPTBP1-1	5'-GCTTCTGCAGCAAACGGAAAT-3'
shFUS-2	5'-GATCAATCCTCCATGAGTA-3'	shPTBP1-2	5'-GCGTGAAGATCCTGTTCAATA-3'
shFUS-3	5'-GATGAATGCAACCAGTGTAAGG-3'	shPTBP1-3	5'-GCTCAACGTCAAGTACAACAAT-3'
shFUS-4	5'-GCAATTCCTGATCACCCAAGGG-3'	shPTBP1-4	5'-GACGCGGAGAGAACCGATTAAA-3'

Fig. 1 Effect of FUS on CML cell proliferation

Fig. 2 Effect of knockdown of FUS on cell cycle progression and apoptosis in CML cells

Fig. 3 Nuclear FUS participates in transcriptional activation by regulating chromatin spatial conformation

Fig. 4 FUS potentially cooperates with PTBP1 in the regulation of CML cells

References 18

[1]	GEUENS T, BOUHY D, TIMMERMAN V. The hnRNP family: insights into their role in health and disease[J]. Human Gene., 2016, 135(8): 851-867.
[2]	LI B, WEN M, GAO F, et al.. Regulation of HNRNP family by post-translational modifications in cancer[J/OL]. Cell Death Discov., 2024, 10: 427[2025-12-25]. .
[3]	JI Y, LI F, QIAO Y. Modulating liquid-liquid phase separation of FUS: mechanisms and strategies[J]. J. Mater. Chem. B, 2022, 10(42): 8616-8628.
[4]	LEVONE B R, LENZKEN S C, ANTONACI M, et al.. FUS-dependent liquid-liquid phase separation is important for DNA repair initiation[J/OL]. J. Cell Biol., 2021, 220(5): e202008030[2025-12-25]. .
[5]	SHAO Y, SHU X, LU Y, et al.. A chaperone-like function of FUS ensures TAZ condensate dynamics and transcriptional activation[J]. Nat. Cell Biol., 2024, 26(1): 86-99.
[6]	YU Y, REED R. FUS functions in coupling transcription to splicing by mediating an interaction between RNAP Ⅱ and U1 snRNP[J]. Proc. Natl. Acad. Sci. USA, 2015, 112(28): 8608-8613.
[7]	IANNONE C, KAINOV Y, ZHURAVSKAYA A, et al.. PTBP1-activated co-transcriptional splicing controls epigenetic status of pluripotent stem cells[J]. Mol. Cell, 2023, 83(2): 203-218.
[8]	MILLS K I, WALSH V, GILKES A F, et al.. High FUS/TLS expression in acute myeloid leukaemia samples[J]. Br. J. Haematol., 2000, 108(2): 316-321.
[9]	WALSBY E J, GILKES A F, TONKS A, et al.. FUS expression alters the differentiation response to all-trans retinoic acid in NB4 and NB4R2 cells[J]. Br. J. Haematol., 2007, 139(1): 94-97.
[10]	DHIR A, ETHELL A, WATKINS R, et al.. The splicing factor PTBP1 interacts with RUNX1 and is required for leukemia cell survival[J]. Leukemia, 2026, 40(1): 138-151.
[11]	JABBOUR E, KANTARJIAN H. Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring[J]. Am. J. Hematol., 2024, 99(11): 2191-2212.
[12]	SUN C, XU X, CHEN Z, et al.. Selective translational control by PABPC1 phase separation regulates blast crisis and therapy resistance in chronic myeloid leukaemia[J]. Nat. Cell Biol., 2025, 27(4): 683-695.
[13]	YANG L, GAL J, CHEN J, et al.. Self-assembled FUS binds active chromatin and regulates gene transcription[J]. Proc. Natl. Acad. Sci. USA, 2014, 111(50): 17809-17814.
[14]	DAVIS R B, SUPAKAR A, RANGANATH A K, et al.. Heterotypic interactions can drive selective co-condensation of prion-like low-complexity domains of FET proteins and mammalian SWI/SNF complex[J/OL]. Nat. Commun., 2024, 15: 1168[2025-12-25]. .
[15]	SABARI B R, DALL'AGNESE A, BOIJA A, et al.. Coactivator condensation at super-enhancers links phase separation and gene control[J/OL]. Science, 2018, 361(6400): eaar3958[2025-12-25]. .
[16]	ZHOU Z, ZHUO N, ZHOU Y, et al.. Identification of the characteristics and prognostic impact of FUS ERG and RUNX1 CBFA2T3 fusion genes in adult acute myeloid leukemia patients[J]. Am. J. Hematol., 2024, 99(7): 1441-1444.
[17]	PERROTTI D, BONATTI S, TROTTA R, et al.. TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL‐mediated leukemogenesis[J]. EMBO J., 1998, 17(15): 4442-4455.
[18]	BARIK B, LAMA S, IS S, et al.. PTBP2 promotes cell survival and autophagy in chronic myeloid leukemia by stabilizing BNIP3[J/OL]. Cell Death Dis., 2025, 16: 195[2025-12-25]. .

FUS and PTBP1 Cooperatively Promote Chronic Myeloid Leukemia Progression via Transcriptional and Post-transcriptional Regulation

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 5

References 18

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Xiying LIU, Qiangrui LIU. Exploring the Mechanism of Wogonin in Cerebral Ischemia-reperfusion Injury Using Network Pharmacology [J]. Current Biotechnology, 2026, 16(3): 719-728.
[2]	Ming LI, Nannan QU, Wei LI. Technical Breakthroughs and Regulatory Challenges of Continuous Bioprocessing in Antibody Drug Production [J]. Current Biotechnology, 2025, 15(5): 845-853.
[3]	Xu ZHU, Yingnan ZHANG, Jinfa MA, Lihong SHI. The Role of Ptbp1 in T Cell Acute Lymphoblastic Leukemia Mice [J]. Current Biotechnology, 2025, 15(2): 341-348.
[4]	Qing YANG, Gang NIU, Jiangang KANG, Chenfang WANG, Kaili DUAN. Pathogenic Mechanism of Fusarium graminearum and its Molecular Interaction with Wheat [J]. Current Biotechnology, 2024, 14(5): 738-744.
[5]	Kaifei XI, Chengjie LI, Yi DING, Wei GUO. Highly Efficient Gene Knockout Method in Fusarium verticillioides Using Nonhomologous End-joining Deficiency [J]. Current Biotechnology, 2024, 14(3): 422-432.
[6]	Liwen WANG, Jiangkun WANG, Bingbing WANG, Jianhong XU, Jianrong SHI, Xin LIU. Roles of Fusarium Toxins in Plant-pathogen Interaction [J]. Current Biotechnology, 2024, 14(2): 182-188.
[7]	Haitao CAO, Jing ZHU, Haibo ZENG, Yanchen LIU. Research on Feature Selection of Gut Microbiota and Disease Prediction Model Based on Weighted Average [J]. Current Biotechnology, 2023, 13(5): 798-806.
[8]	Xiaoyan PENG, Panpan LU, Zuquan HU. Prokaryotic Expression of the RBD Protein of SARS-CoV-2 and its Polyclonal Antibodies Preparation [J]. Current Biotechnology, 2023, 13(1): 102-106.
[9]	Jing CHENG, Guo ZHANG, Wenfei ZHANG, Liquan WU, Zhibiao CHEN. Mechanism and Research Progress of SIRT6 in Ischemia Reperfusion Injury [J]. Current Biotechnology, 2022, 12(6): 875-879.
[10]	Yiqi YANG, Zhigao ZHANG, Xiaolong YOU, Jing ZHANG, Guanfeng LIN, Yingsong WU. Development and Application of Monoclonal Antibody-based Drug [J]. Current Biotechnology, 2022, 12(3): 358-365.
[11]	Yibo MA, Yuechen CHANG, Ketao MA, Li LI, Qinzhang WANG, Yinglong LI. Effects of Estrogen on the Expression of Cx43 Protein in Renal Tubular Epithelial Cells of SD Rats with Ischemia⁃reperfusion [J]. Current Biotechnology, 2022, 12(3): 452-459.
[12]	Jinping XIAO, Cheng LI, Yundi CAO, Zhijian SUN, Ping KANG, Xiaomei LAN. Research Progress on the Relationship Between RET Protooncogene and Tumor [J]. Current Biotechnology, 2022, 12(1): 57-62.
[13]	Peisen SU. Research Advances in Wheat FHB Resistance Mechanism [J]. Current Biotechnology, 2021, 11(5): 599-609.
[14]	Yong ZHANG, Wenjing HU, Chunmei ZHANG, Zhengning JIANG, Guofeng LV, Derong GAO. Analysis and Prospect of Fusarium Head Blight Resistance for New Wheat Varieties (Lines) Bred During “the 13th Five‑year Plan” [J]. Current Biotechnology, 2021, 11(5): 590-598.
[15]	Wenling ZHAI, Caiyun LIU, Ying LIU, Bisheng FU, Jin CAI, Wei GUO, Qiaofeng ZHANG, Jizhong WU. Phenotypic and Molecular Identification of New Wheat Germplasm Resistant to Fusarium Head Blight [J]. Current Biotechnology, 2021, 11(5): 581-589.