Advances on KPNA2 in liver cancer

doi:10.3760/cma.j.cn371439-20231026-00029

Abstract

Abstract:

Karyopherin α2 （KPNA2）， a key protein molecule that regulates the exchange of substances between the nucleus and the cytoplasm， plays an important role in the nucleocytoplasmic transport pathway. In recent years， an increasing number of studies have shown that KPNA2 is involved in a variety of cellular life activities and plays a significant part in viral infection， cell proliferation， immune response and tumor metastasis. Further study of the mechanism of KPNA2 in promoting the hepatocarcinogenesis and exploring its role in the development of liver cancer may provide new ideas for the diagnosis， treatment， and prognosis of liver cancer.

Key words: Liver neoplasms, Early diagnosis, Therapy, Prognosis, KPNA2

Peng Qin, Cai Yuting, Wang Wei. Advances on KPNA2 in liver cancer[J]. Journal of International Oncology, 2024, 51(3): 181-185.

References 38

[1]	Rumgay H, Ferlay J, de Martel C, et al. Global, regional and national burden of primary liver cancer by subtype[J]. Eur J Cancer, 2022, 161: 108-118. DOI: 10.1016/j.ejca.2021.11.023.
[2]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[3]	Cheung TT, Wai-Hung Ho D, Lyu SX, et al. Multimodal integrative genomics and pathology analyses in neoadjuvant nivolumab treatment for intermediate and locally advanced hepatocellular carcinoma[J]. Liver Cancer, 2024, 13(1): 70-88. DOI: 10.1159/000531176.
[4]	Zhang L, Zhang YM, Wang CD, et al. Integrated single-cell RNA sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer[J]. Signal Transduct Target Ther, 2022, 7(1): 9. DOI: 10.1038/s41392-021-00824-9.
[5]	Jensen JB, Munksgaard PP, Sørensen CM, et al. High expression of karyopherin-α 2 defines poor prognosis in non-muscle-invasive bladder cancer and in patients with invasive bladder cancer undergoing radical cystectomy[J]. Eur Urol, 2011, 59(5): 841-848. DOI: 10.1016/j.eururo.2011.01.048.
[6]	Guo XG, Wang ZH, Zhang JN, et al. Upregulated KPNA2 promotes hepatocellular carcinoma progression and indicates prognostic significance across human cancer types[J]. Acta Biochim Biophys Sin (Shanghai), 2019, 51(3): 285-292. DOI: 10.1093/abbs/gmz003.
[7]	Han Y, Wang X. The emerging roles of KPNA2 in cancer[J]. Life Sci, 2020, 241: 117140. DOI: 10.1016/j.lfs.2019.117140.
[8]	Yang XY, Wang H, Zhang L, et al. Novel roles of karyopherin subunit alpha 2 in hepatocellular carcinoma[J]. Biomed Pharmacother, 2023, 163: 114792. DOI: 10.1016/j.biopha.2023.114792.
[9]	Nakanishi A, Okumura H, Hashita T, et al. Ivermectin inhibits HBV entry into the nucleus by suppressing KPNA2[J]. Viruses, 2022, 14(11): 2468. DOI: 10.3390/v14112468.
[10]	Zhao LN, Yuan HF, Wang YF, et al. HBV confers innate immune evasion through triggering HAT1/acetylation of H4K5/H4K12/miR-181a-5p or KPNA2/cGAS-STING/IFN-Ⅰ signaling[J]. J Med Virol, 2023, 95(7): e28966. DOI: 10.1002/jmv.28966.
[11]	Gao CL, Wang GW, Yang GQ, et al. Karyopherin subunit-α2 expression accelerates cell cycle progression by upregulating CCNB2 and CDK1 in hepatocellular carcinoma[J]. Oncol Lett, 2018, 15(3): 2815-2820. DOI: 10.3892/ol.2017.7691.
[12]	Zeng FC, Luo LM, Li DY, et al. KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway[J]. J Transl Med, 2021, 19(1): 112. DOI: 10.1186/s12967-021-02709-5. pmid: 33731128
[13]	Chen T, Liu R, Niu Y, et al. HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway[J]. Cell Death Dis, 2021, 12(12): 1152. DOI: 10.1038/s41419-021-04449-2. pmid: 34903711
[14]	Chakraborty S, Anand S, Coe S, et al. The PCOS-NAFLD multidisease phenotype occurred in medaka fish four generations after the removal of bisphenol a exposure[J]. Environ Sci Technol, 2023, 57(34): 12602-12619. DOI: 10.1021/acs.est.3c01922.
[15]	Romanovsky E, Kluck K, Ourailidis I, et al. Homogenous TP53mut-associated tumor biology across mutation and cancer types revealed by transcriptome analysis[J]. Cell Death Discov, 2023, 9(1): 126. DOI: 10.1038/s41420-023-01413-1. pmid: 37059713
[16]	Tang GF, Zhao HB, Xie ZT, et al. Long non-coding RNA HAGLROS facilitates tumorigenesis and progression in hepatocellular carcinoma by sponging miR-26b-5p to up-regulate karyopherin α2 (KPNA2) and inactivate p53 signaling[J]. Bioengineered, 2022, 13(3): 7829-7846. DOI: 10.1080/21655979.2022.2049472. pmid: 35291921
[17]	Park SH, Ham S, Lee A, et al. NLRP3 negatively regulates Treg differentiation through KPNA2-mediated nuclear translocation[J]. J Biol Chem, 2019, 294(47): 17951-17961. DOI: 10.1074/jbc.RA119.010545.
[18]	Zhang JZ, Zhang XZ, Wang LX, et al. Multiomics-based analyses of KPNA2 highlight its multiple potentials in hepatocellular carcinoma[J]. PeerJ, 2021, 9: e12197. DOI: 10.7717/peerj.12197.
[19]	Dou CW, Zhou ZY, Xu QR, et al. Hypoxia-induced TUFT1 promotes the growth and metastasis of hepatocellular carcinoma by activating the Ca²⁺/PI3K/AKT pathway[J]. Oncogene, 2019, 38(8): 1239-1255. DOI: 10.1038/s41388-018-0505-8.
[20]	Wang P, Zhao YH, Liu KJ, et al. Wip1 cooperates with KPNA2 to modulate the cell proliferation and migration of colorectal cancer via a p53-dependent manner[J]. J Cell Biochem, 2019, 120(9): 15709-15718. DOI: 10.1002/jcb.28840. pmid: 31127650
[21]	Jia YJ, Wang Q, Liang ML, et al. KPNA2 promotes angiogenesis by regulating STAT3 phosphorylation[J]. J Transl Med, 2022, 20(1): 627. DOI: 10.1186/s12967-022-03841-6. pmid: 36578083
[22]	Cai YC, Fu Y, Liu CC, et al. Stathmin 1 is a biomarker for diagnosis of microvascular invasion to predict prognosis of early hepatocellular carcinoma[J]. Cell Death Dis, 2022, 13(2): 176. DOI: 10.1038/s41419-022-04625-y. pmid: 35210426
[23]	Drucker E, Holzer K, Pusch S, et al. Karyopherin α2-dependent import of E2F1 and TFDP1 maintains protumorigenic stathmin expression in liver cancer[J]. Cell Commun Signal, 2019, 17(1): 159. DOI: 10.1186/s12964-019-0456-x. pmid: 31783876
[24]	Wang WJ, Miyamoto Y, Chen BB, et al. Karyopherin α deficiency contributes to human preimplantation embryo arrest[J]. J Clin Invest, 2023, 133(2): e159951. DOI: 10.1172/JCI159951.
[25]	Radhakrishnan K, Park SJ, Kim SW, et al. Karyopherin α-2 mediates MDC1 nuclear import through a functional nuclear localization signal in the tBRCT domain of MDC1[J]. Int J Mol Sci, 2020, 21(7): 2650. DOI: 10.3390/ijms21072650.
[26]	Hu B, Qu C, Qi WJ, et al. Development and verification of the glycolysis-associated and immune-related prognosis signature for hepatocellular carcinoma[J]. Front Genet, 2022, 13: 955673. DOI: 10.3389/fgene.2022.955673.
[27]	Brownlee C, Heald R. Importin α partitioning to the plasma membrane regulates intracellular scaling[J]. Cell, 2019, 176(4): 805-815.e8. DOI: 10.1016/j.cell.2018.12.001. pmid: 30639102
[28]	Ding F, Li JP, Zhang Y, et al. Identifying a novel endoplasmic reticulum-related prognostic model for hepatocellular carcinomas[J]. Oxid Med Cell Longev, 2022, 2022: 8248355. DOI: 10.1155/2022/8248355.
[29]	Pan Y, Zhang YR, Lu ZM, et al. The role of KPNA2 as a monotonically changing differentially expressed gene in the diagnosis, risk stratification, and chemotherapy sensitivity of chronic hepatitis B-liver cirrhosis-hepatocellular carcinoma[J]. J Cancer Res Clin Oncol, 2023, 149(15): 13753-13771. DOI: 10.1007/s00432-023-05213-z. pmid: 37526663
[30]	Xia JG, Wu C, Tang YH, et al. CircMYH9 increases KPNA2 mRNA stability to promote hepatocellular carcinoma progression in an EIF4A3-dependent manner[J]. Am J Cancer Res, 2022, 12(9): 4361-4372. DOI:. pmid: 36225644
[31]	Lin CZ, Ou RW, Hu YH. Lentiviral-mediated microRNA-26b up-regulation inhibits proliferation and migration of hepatocellular carcinoma cells[J]. Kaohsiung J Med Sci, 2018, 34(10): 547-555. DOI: 10.1016/j.kjms.2018.05.003.
[32]	Zan Y, Wang BF, Liang L, et al. MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2[J]. J Exp Clin Cancer Res, 2019, 38(1): 182. DOI: 10.1186/s13046-019-1175-2. pmid: 31046781
[33]	Shi CL, Sun L, Liu SZ, et al. Overexpression of karyopherin subunit alpha 2 (KPNA2) predicts unfavorable prognosis and promotes bladder cancer tumorigenicity via the P53 pathway[J]. Med Sci Monit, 2020, 26: e921087. DOI: 10.12659/MSM.921087.
[34]	Sun Y, Li W, Li X, et al. Oncogenic role of karyopherin α2 (KPNA2) in human tumors: a pan-cancer analysis[J]. Comput Biol Med, 2021, 139: 104955. DOI: 10.1016/j.compbiomed.2021.104955.
[35]	Chen PF, Li QH, Zeng LR, et al. A 4-gene prognostic signature predicting survival in hepatocellular carcinoma[J]. J Cell Biochem, 2019, 120(6): 9117-9124. DOI: 10.1002/jcb.28187.
[36]	Zhang Q, Jin XY, Shi WB, et al. A long non-coding RNA LINC00461-dependent mechanism underlying breast cancer invasion and migration via the miR-144-3p/KPNA2 axis[J]. Cancer Cell Int, 2020, 20: 137. DOI: 10.1186/s12935-020-01221-y. pmid: 32355466
[37]	Zhao Q, Zhang Y, Shao SC, et al. Identification of hub genes and biological pathways in hepatocellular carcinoma by integrated bioinformatics analysis[J]. PeerJ, 2021, 9: e10594. DOI: 10.7717/peerj.10594.
[38]	Lai WW, Li DF, Ge Q, et al. A five-LLPS gene risk score prognostic signature predicts survival in hepatocellular carcinoma[J]. Int J Genomics, 2023, 2023: 7299276. DOI: 10.1155/2023/7299276.