Open Access

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

  • Published online on: March 19, 2021     https://doi.org/10.3892/ol.2021.12664
  • Article Number: 403
  • Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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May-2021
Volume 21 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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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