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Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549

  • Authors:
    • Lihong Shao
    • Yuyu Zhang
    • Xinkou Gong
    • Zhuo Dong
    • Wei Wei
    • Hongyan Sun
    • Ran Sun
    • Lele Cong
    • Xianling Cong
    • Shunzi Jin
  • View Affiliations / Copyright

    Affiliations: National Health Commission Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin 130000, P.R. China, Department Radiology, 2nd Hospital Affiliated to Jilin University, Changchun, Jilin 130000, P.R. China, Scientific Research Center, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China
    Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 403
    |
    Published online on: March 19, 2021
       https://doi.org/10.3892/ol.2021.12664
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Abstract

Radiotherapy is widely used in the management of lung cancer, and physicians are aware that the effect of radiotherapy is dependent on radiosensitivity. Although a series of blockers and activators targeting molecules related to radioresistance have been developed as radiation sensitizers, compensatory mechanisms or drug resistance limits their clinical efficacy. The identification of a key molecule related to lung cancer cell radioresistance or an effective molecular target is a challenging but important problem in radiation oncology. A previous study found that neuropilin 1 (NRP1) is related to radioresistance in A549 cells and is associated with VEGF, PI3K‑Akt, MAPK‑ERK, P38, NF‑κβ and TGF‑β. Inhibition of NRP1 can increase the radiosensitivity of A549 cells. Therefore, NRP1 may be a molecular target for radiotherapy‑sensitizing drugs in lung cancer. The present study investigated the key downstream genes of NRP1, verified their regulation and clarified their roles in regulating lung cancer radioresistance. NRP1 positively regulated the downstream homeobox genes (HOXs) HOXA6, HOXA9 and mixed lineage leukaemia 5 (MLL5) in addition to MLL5‑regulated HOXA6 and HOXA9, but these genes did not regulate NRP1. MLL5, HOXA6 and HOXA9 levels were decreased in tumour tissues and positively correlated with NRP1. All of these genes were induced by ionizing radiation in vivo and in vitro. NRP1 expression was significantly lower in squamous cell carcinoma compared with that in adenocarcinoma, and lymph node metastasis occurred more often in patients with lung cancer with high MLL5 and NRP1 expression compared with patients with low MLL5 and NRP1 expression. Collectively, these data confirmed that NRP1 is associated with MLL5 and regulates radioresistance through HOXA6 and HOXA9.
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View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: A Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Mou J, Hu T, Wang Z, Chen W, Wang Y and Zhang W: ATM gene polymorphisms are associated with poor prognosis of non-small cell lung cancer receiving radiation therapy. Aging (Albany NY). 12:7465–7479. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Zhou R, Xu T, Nguyen QN, Liu Y, Yang J, Komaki R, Gomez DR and Liao Z: Radiation dose, local disease progression, and overall survival in patients with inoperable non-small cell lung cancer after concurrent chemoradiation therapy. Int J Radiat Oncol Biol Phys. 100:452–461. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Nasarre C, Roth M, Jacob L, Roth L, Koncina E, Thien A, Labourdette G, Poulet P, Hubert P, Crémel G, et al: Peptide-based interference of the transmembrane domain of neuropilin-1 inhibits glioma growth in vivo. Oncogene. 29:2381–2392. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Roth L, Nasarre C, Dirrig-Grosch S, Aunis D, Crémel G, Hubert P and Bagnard D: Transmembrane domain interactions control biological functions of neuropilin-1. Mol Biol Cell. 19:646–654. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Nakamura F and Goshima Y: Structural and functional relation of neuropilins. Adv Exp Med Biol. 515:55–69. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Giordano S, Corso S, Conrotto P, Artigiani S, Gilestro G, Barberis D, Tamagnone L and Comoglio PM: The semaphorin 4D receptor controls invasive growth by coupling with Met. Nat Cell Biol. 4:720–724. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Hong TM, Chen YL, Wu YY, Yuan A, Chao YC, Chung YC, Wu MH, Yang SC, Pan SH, Shih JY, et al: Targeting neuropilin 1 as an antitumor strategy in lung cancer. Clin Cancer Res. 13:4759–4768. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Osada H, Tokunaga T, Nishi M, Hatanaka H, Abe Y, Tsugu A, Kijima H, Yamazaki H, Ueyama Y and Nakamura M: Overexpression of the neuropilin 1 (NRP1) gene correlated with poor prognosis in human glioma. Anticancer Res. 24:547–552. 2004.PubMed/NCBI

10 

Glinka Y, Mohammed N, Subramaniam V, Jothy S and Prud'homme GJ: Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation. Biochem Biophys Res Commun. 425:775–780. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Dong JC, Gao H, Zuo SY, Zhang HQ, Zhao G, Sun SL, Han HL, Jin LL, Shao LH, Wei W and Jin SZ: Neuropilin 1 expression correlates with the radio-resistance of human non-small-cell lung cancer cells. J Cell Mol Med. 19:2286–2295. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Xiong K, Shao LH, Zhang HQ, Jin L, Wei W, Dong Z, Zhu YQ, Wu N, Jin SZ and Xue LX: MicroRNA-9 functions as a tumor suppressor and enhances radio-sensitivity in radio-resistant A549 cells by targeting neuropilin 1. Oncol Lett. 15:2863–2870. 2018.PubMed/NCBI

13 

Gorski DH and Walsh K: The role of homeobox genes in vascular remodeling and angiogenesis. Circ Res. 87:865–872. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Kappen C: Developmental patterning as a quantitative trait: Genetic modulation of the Hoxb6 mutant skeletal phenotype. PLoS One. 11:e01460192016. View Article : Google Scholar : PubMed/NCBI

15 

Denans N, Iimura T and Pourquie O: Hox genes control vertebrate body elongation by collinear Wnt repression. Elife. 4:e043792015. View Article : Google Scholar

16 

Paço A, Aparecida de Bessa Garcia S, Leitão Castro J, Costa-Pinto AR and Freitas R: Roles of the HOX proteins in cancer invasion and metastasis. Cancers (Basel). 13:102020. View Article : Google Scholar

17 

Morgan R, Simpson G, Gray S, Gillett C, Tabi Z, Spicer J, Harrington KJ and Pandha HS: HOX transcription factors are potential targets and markers in malignant mesothelioma. BMC Cancer. 16:852016. View Article : Google Scholar : PubMed/NCBI

18 

Steger J, Füller E, Garcia-Cuellar MP, Hetzner K and Slany RK: Insulin-like growth factor 1 is a direct HOXA9 target important for hematopoietic transformation. Leukemia. 29:901–908. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Larsen BM, Hrycaj SM, Newman M, Li Y and Wellik DM: Mesenchymal Hox6 function is required for mouse pancreatic endocrine cell differentiation. Development. 142:3859–3868. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Chiba N, Comaills V, Shiotani B, Takahashi F, Shimada T, Tajima K, Winokur D, Hayashida T, Willers H, Brachtel E, et al: Homeobox B9 induces epithelial-to-mesenchymal transition-associated radioresistance by accelerating DNA damage responses. Proc Natl Acad Sci USA. 109:2760–2765. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Slany RK: MLL fusion proteins and transcriptional control. Biochim Biophys Acta Gene Regul Mech. 1863:1945032020. View Article : Google Scholar : PubMed/NCBI

22 

Cheng F, Liu J, Zhou SH, Wang XN, Chew JF and Deng LW: RNA interference against mixed lineage leukemia 5 resulted in cell cycle arrest. Int J Biochem Cell Biol. 40:2472–2481. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Emerling BM, Bonifas J, Kratz CP, Donovan S, Taylor BR, Green ED, Le Beau MM and Shannon KM: MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia. Oncogene. 21:4849–4854. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Lee KH, Kim BC, Jeong CW, Ku JH, Kim HH and Kwak C: MLL5, a histone modifying enzyme, regulates androgen receptor activity in prostate cancer cells by recruiting co-regulators, HCF1 and SET1. BMB Rep. 53:634–639. 2020. View Article : Google Scholar : PubMed/NCBI

25 

Madan V, Madan B, Brykczynska U, Zilbermann F, Hogeveen K, Döhner K, Döhner H, Weber O, Blum C, Rodewald HR, et al: Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog MLL5. Blood. 113:1444–1454. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Heuser M, Yap DB, Leung M, de Algara TR, Tafech A, McKinney S, Dixon J, Thresher R, Colledge B, Carlton M, et al: Loss of MLL5 results in pleiotropic hematopoietic defects, reduced neutrophil immune function, and extreme sensitivity to DNA demethylation. Blood. 113:1432–1443. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Milne TA: MLL5 expression as a biomarker for DNA hypermethylation and sensitivity to epigenetic therapy. Haematologica. 99:1405–1407. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Zhou P, Wang Z, Yuan X, Zhou C, Liu L, Wan X, Zhang F, Ding X, Wang C, Xiong S, et al: Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with host cell factor-1 (HCF-1). J Biol Chem. 288:17532–17543. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Yan Y, Greer PM, Cao PT, Kolb RH and Cowan KH: RAC1 GTPase plays an important role in gamma-irradiation induced G2/M checkpoint activation. Breast Cancer Res. 14:R602012. View Article : Google Scholar : PubMed/NCBI

31 

Chen Z, Gao H, Dong Z, Shen Y, Wang Z, Wei W, Yi J, Wang R, Wu N and Jin S: NRP1 regulates radiation-induced EMT via TGF-β/Smad signaling in lung adenocarcinoma cells. Int J Radiat Biol. 96:1281–1295. 2020. View Article : Google Scholar : PubMed/NCBI

32 

Vanveldhuizen PJ, Zulfiqar M, Banerjee S, Cherian R, Saxena NK, Rabe A, Thrasher JB and Banerjee SK: Differential expression of neuropilin-1 in malignant and benign prostatic stromal tissue. Oncol Rep. 10:1067–1071. 2003.PubMed/NCBI

33 

Pawlik TM and Keyomarsi K: Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys. 59:928–942. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Shao L, Zhang Y, Gong X, Dong Z, Wei W, Sun H, Sun R, Cong L, Cong X, Jin S, Jin S, et al: Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549. Oncol Lett 21: 403, 2021.
APA
Shao, L., Zhang, Y., Gong, X., Dong, Z., Wei, W., Sun, H. ... Jin, S. (2021). Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549. Oncology Letters, 21, 403. https://doi.org/10.3892/ol.2021.12664
MLA
Shao, L., Zhang, Y., Gong, X., Dong, Z., Wei, W., Sun, H., Sun, R., Cong, L., Cong, X., Jin, S."Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549". Oncology Letters 21.5 (2021): 403.
Chicago
Shao, L., Zhang, Y., Gong, X., Dong, Z., Wei, W., Sun, H., Sun, R., Cong, L., Cong, X., Jin, S."Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549". Oncology Letters 21, no. 5 (2021): 403. https://doi.org/10.3892/ol.2021.12664
Copy and paste a formatted citation
x
Spandidos Publications style
Shao L, Zhang Y, Gong X, Dong Z, Wei W, Sun H, Sun R, Cong L, Cong X, Jin S, Jin S, et al: Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549. Oncol Lett 21: 403, 2021.
APA
Shao, L., Zhang, Y., Gong, X., Dong, Z., Wei, W., Sun, H. ... Jin, S. (2021). Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549. Oncology Letters, 21, 403. https://doi.org/10.3892/ol.2021.12664
MLA
Shao, L., Zhang, Y., Gong, X., Dong, Z., Wei, W., Sun, H., Sun, R., Cong, L., Cong, X., Jin, S."Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549". Oncology Letters 21.5 (2021): 403.
Chicago
Shao, L., Zhang, Y., Gong, X., Dong, Z., Wei, W., Sun, H., Sun, R., Cong, L., Cong, X., Jin, S."Effects of MLL5 and HOXA regulated by NRP1 on radioresistance in A549". Oncology Letters 21, no. 5 (2021): 403. https://doi.org/10.3892/ol.2021.12664
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