Heterogeneous nuclear ribonucleoprotein H1 and its function in tumor development and metastasis

doi:10.3969/j.issn.1674-8115.2024.12.016

Abstract

Abstract:

Heterogeneous nuclear ribonucleoprotein (hnRNP) and heterogeneous nuclear RNA (hnRNA) form complexes that regulate RNA splicing and transportation. hnRNPH1 is a member of the hnRNP family of proteins and plays an important role in physiological processes, including embryonic development of the nervous and reproductive systems. hnRNPH1 is highly expressed in various tumor tissues and tumor cells, and its overexpression correlates with poor prognosis in patients. hnRNPH1 enhances tumor cell proliferation and metastasis through the regulation of alternative splicing of genes, modulation of gene expression, formation of fusion genes with other genes, and involvement in epigenetic regulation.Recent studies have shown that hnRNPH1 could serve as a potential biomarker for certain tumors, and hnRNPH1-targeting drugs show preliminary efficacy in a mouse model of melanoma. This article reviews the role and research progress of hnRNPH1 in the initiation and progression of malignant tumors.

Key words: hnRNPH1, tumor, gene, lncRNA, miRNA, alternative splicing

CLC Number:

R730.7

ZHANG Zongwen, FENG Li, FAN Zhisong. Heterogeneous nuclear ribonucleoprotein H1 and its function in tumor development and metastasis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(12): 1615-1620.

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References 46

1	LU Y, WANG X Y, GU Q, et al. Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets[J]. Cell Death Discov, 2022, 8: 337.
2	GILLENTINE M A, WANG T Y, HOEKZEMA K, et al. Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders[J]. Genome Med, 2021, 13(1): 63.
3	VAN EEKELEN C A, VAN VENROOIJ W J. hnRNA and its attachment to a nuclear protein matrix[J]. J Cell Biol, 1981, 88(3): 554-563.
4	FENG S L, LI J M, WEN H, et al. hnRNPH1 recruits PTBP2 and SRSF3 to modulate alternative splicing in germ cells[J]. Nat Commun, 2022, 13: 3588.
5	BROWNMILLER T, CAPLEN N J. The HNRNPF/H RNA binding proteins and disease[J]. Wiley Interdiscip Rev RNA, 2023, 14(5): e1788.
6	HAN S P, TANG Y H, SMITH R. Functional diversity of the hnRNPs: past, present and perspectives[J]. Biochem J, 2010, 430(3): 379-392.
7	LUNDE B M, MOORE C, VARANI G. RNA-binding proteins: modular design for efficient function[J]. Nat Rev Mol Cell Biol, 2007, 8: 479-490.
8	ALKAN S A, MARTINCIC K, MILCAREK C. The hnRNPs F and H₂ bind to similar sequences to influence gene expression[J]. Biochem J, 2006, 393(pt 1): 361-371.
9	VO T, BROWNMILLER T, HALL K, et al. HNRNPH1 destabilizes the G-quadruplex structures formed by G-rich RNA sequences that regulate the alternative splicing of an oncogenic fusion transcript[J]. Nucleic Acids Res, 2022, 50(11): 6474-6496.
10	VAN DUSEN C M, YEE L, MCNALLY L M, et al. A glycine-rich domain of hnRNP H/F promotes nucleocytoplasmic shuttling and nuclear import through an interaction with transportin 1[J]. Mol Cell Biol, 2010, 30(10): 2552-2562.
11	COLES J L, HALLEGGER M, SMITH C W. A nonsense exon in the Tpm1 gene is silenced by hnRNP H and F[J]. RNA, 2009, 15(1): 33-43.
12	XU J, LU Z, XU M, et al. A heroin addiction severity-associated intronic single nucleotide polymorphism modulates alternative pre-mRNA splicing of the μ opioid receptor gene OPRM1 via hnRNPH interactions[J]. J Neurosci, 2014, 34(33): 11048-11066.
13	LAFORCE G R, PHILIPPIDOU P, SCHAFFER A E. mRNA isoform balance in neuronal development and disease[J]. Wiley Interdiscip Rev RNA, 2023, 14(3): e1762.
14	GRAMMATIKAKIS I, ZHANG P, PANDA A C, et al. Alternative splicing of neuronal differentiation factor TRF2 regulated by HNRNPH1/H2[J]. Cell Rep, 2016, 15(5): 926-934.
15	ZHANG P, CASADAY-POTTS R, PRECHT P, et al. Nontelomeric splice variant of telomere repeat-binding factor 2 maintains neuronal traits by sequestering repressor element 1-silencing transcription factor[J]. Proc Natl Acad Sci USA, 2011, 108(39): 16434-16439.
16	FENG S, WEN H, LIU K, et al. hnRNPH1 establishes Sertoli-germ cell crosstalk through cooperation with PTBP1 and AR, and is essential for male fertility in mice[J]. Development, 2023, 150(3): dev201040.
17	马冉冉. 长链非编码RNA AK126420通过其结合蛋白HNRNPH1促进胃癌转移的作用机制研究[D]. 济南: 山东大学, 2019.
	MA R R. The mechanism of lncRNA AK126420 promoting gastric cancer metastasis through its binding protein HNRNPH1[D]. Jinan: Shandong University, 2019.
18	XU H, DONG X, CHEN Y, et al. Serum exosomal hnRNPH1 mRNA as a novel marker for hepatocellular carcinoma[J]. Clin Chem Lab Med, 2018, 56(3): 479-484.
19	LUDVIGSEN M, THORLACIUS-USSING L, VORUM H, et al. Proteomic characterization of colorectal cancer tissue from patients identifies novel putative protein biomarkers[J]. Curr Issues Mol Biol, 2021, 43(2): 1043-1056.
20	YANG Y, JIA D, KIM H, et al. Dysregulation of miR-212 promotes castration resistance through hnRNPH1-mediated regulation of AR and AR-V7: implications for racial disparity of prostate cancer[J]. Clin Cancer Res, 2016, 22(7): 1744-1756.
21	LI X J, QIAN X, PENG L X, et al. A splicing switch from ketohexokinase-C to ketohexokinase-A drives hepatocellular carcinoma formation[J]. Nat Cell Biol, 2016, 18: 561-571.
22	DENG Q, WU M L, DENG J. USP36 promotes tumor growth of non-small cell lung cancer via increasing KHK-A expression by regulating c-MYC-hnRNPH1/H2 axis[J]. Hum Cell, 2022, 35(2): 694-704.
23	GAUTREY H, JACKSON C, DITTRICH A L, et al. SRSF3 and hnRNP H1 regulate a splicing hotspot of HER2 in breast cancer cells[J]. RNA Biol, 2015, 12(10): 1139-1151.
24	MA Y H, YANG Y, LI J H, et al. NDUFB11 and NDUFS3 regulate arterial atherosclerosis and venous thrombosis: potential markers of atherosclerosis and venous thrombosis[J]. Medicine, 2023, 102(46): e36133.
25	PANELLI D, LORUSSO F P, PAPA F, et al. The mechanism of alternative splicing of the X-linked NDUFB11 gene of the respiratory chain complex I, impact of rotenone treatment in neuroblastoma cells[J]. Biochim Biophys Acta, 2013, 1829(2): 211-218.
26	LIANG Z, WEN C, JIANG H, et al. Protein arginine methyltransferase 5 functions via interacting proteins[J]. Front Cell Dev Biol, 2021, 9: 725301.
27	WEN C, TIAN Z, LI L, et al. SRSF3 and HNRNPH1 regulate radiation-induced alternative splicing of protein arginine methyltransferase 5 in hepatocellular carcinoma[J]. Int J Mol Sci, 2022, 23(23): 14832.
28	BRIDGES M C, DAULAGALA A C, KOURTIDIS A. LNCcation: lncRNA localization and function[J]. J Cell Biol, 2021, 220(2): e202009045.
29	ZONG L, HATTORI N, YASUKAWA Y, et al. LINC00162 confers sensitivity to 5-Aza-2'-deoxycytidine via modulation of an RNA splicing protein, HNRNPH1[J]. Oncogene, 2019, 38: 5281-5293.
30	HILL M, TRAN N. miRNA interplay: mechanisms and consequences in cancer[J]. Dis Model Mech, 2021, 14(4): dmm047662.
31	VOLK N, SHOMRON N. Versatility of microRNA biogenesis[J]. PLoS One, 2011, 6(5): e19391.
32	ZHOU Y J, LI G, WANG J, et al. PD-L1: expression regulation[J]. Blood Sci, 2023, 5(2): 77-91.
33	MINEO M, LYONS S M, ZDIORUK M, et al. Tumor interferon signaling is regulated by a lncRNA INCR1 transcribed from the PD-L1 locus[J]. Mol Cell, 2020, 78(6): 1207-1223.e8.
34	LUO Z L, XIA M Y, SHI W, et al. Human fetal cerebellar cell atlas informs medulloblastoma origin and oncogenesis[J]. Nature, 2022, 612: 787-794.
35	TAKAHASHI K, FUJIYA M, KONISHI H, et al. Heterogenous nuclear ribonucleoprotein H1 promotes colorectal cancer progression through the stabilization of mRNA of sphingosine-1-phosphate lyase 1[J]. Int J Mol Sci, 2020, 21(12): E4514.
36	RAMACHANDRAN B, RAJKUMAR T, GOPISETTY G. Challenges in modeling EWS-FLI1-driven transgenic mouse model for Ewing sarcoma[J]. Am J Transl Res, 2021, 13(11): 12181-12194.
37	GONG H, XUE B, RU J, et al. Targeted therapy for EWS-FLI1 in ewing sarcoma[J]. Cancers (Basel), 2023, 15(16): 4035.
38	LI Y F, BAKKE J, FINKELSTEIN D, et al. HNRNPH1 is required for rhabdomyosarcoma cell growth and survival[J]. Oncogenesis, 2018, 7: 9.
39	OHKI K, KIYOKAWA N, SAITO Y, et al. Clinical and molecular characteristics of MEF2D fusion-positive B-cell precursor acute lymphoblastic leukemia in childhood, including a novel translocation resulting in MEF2D-HNRNPH1 gene fusion[J]. Haematologica, 2019, 104(1): 128-137.
40	WU Y, GUO Q H, JU X Z, et al. HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway[J]. Oncogene, 2021, 40: 4770-4782.
41	CARRON J, DELLA COLETTA R, LOURENÇO G J. Pseudogene transcripts in head and neck cancer: literature review and in silico analysis[J]. Genes (Basel), 2021, 12(8): 1254.
42	LU X J, GAO A M, JI L J, et al. Pseudogene in cancer: real functions and promising signature[J]. J Med Genet, 2015, 52(1): 17-24.
43	QIAN S H, CHEN L, XIONG Y L, et al. Evolution and function of developmentally dynamic pseudogenes in mammals[J]. Genome Biol, 2022, 23(1): 235.
44	XI S Y, CAI H P, LU J B, et al. The pseudogene PRELID1P6 promotes glioma progression via the hnHNPH1-Akt/mTOR axis[J]. Oncogene, 2021, 40: 4453-4467.
45	BERTOLDO J B, MÜLLER S, HÜTTELMAIER S. RNA-binding proteins in cancer drug discovery[J]. Drug Discov Today, 2023, 28(6): 103580.
46	VELAYUTHAM S, SEERATTAN R, SULTAN M, et al. Novel anti-melanoma compounds are efficacious in A375 cell line xenograft melanoma model in nude mice[J]. Biomolecules, 2023, 13(9): 1276.

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