Open Access

Differential MUC22 expression by epigenetic alterations in human lung squamous cell carcinoma and adenocarcinoma

  • Authors:
    • Shuye Lin
    • Cuimeng Tian
    • Jianhui Li
    • Bin Liu
    • Teng Ma
    • Keqiang Chen
    • Wanghua Gong
    • Ji Ming Wang
    • Jiaqiang Huang
  • View Affiliations

  • Published online on: March 26, 2021     https://doi.org/10.3892/or.2021.8029
  • Article Number: 78
  • Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Disruption in mucins (MUCs) is involved in cancer development and metastasis and is thus used as a biomarker. Non‑small cell lung carcinoma (NSCLC) is characterized by heterogeneous genetic and epigenetic alterations. Lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) are the two primary subtypes of NSCLC that require different therapeutic interventions. Here, we report distinct expression and epigenetic alterations in mucin 22 (MUC22), a new MUC family member, in LUSC vs. LUAD. In lung cancer cell lines and tissues, MUC22 was downregulated in LUSC (MUC22Low) but upregulated in LUAD (MUC22High) with co‑expression of MUC21. The aberrant expression of MUC22 was inversely correlated with its promoter hypermethylation in LUSC and hypomethylation in LUAD cells and tissues, respectively. Decreased MUC22 expression in NSCLC cell lines was restored upon treatment with epigenetic modifiers 5‑aza‑2'‑deoxycytidine (5‑Aza) or trichostatin A (TSA), accompanied by reduction in global protein level of histone deacetylase 1 (HDAC1) but increased enrichment of histone H3 lysine 9 acetylation (H3K9ac) specifically in the MUC22 promoter in the SK‑MES‑1 cell line. MUC22 knockdown increased the growth and motility of lung cancer cells and an immortalized human bronchial epithelial BEAS‑2B cell line via NF‑κB activation. Clinically, MUC22Low in LUSC and MUC22High in LUAD were shown to be indicators of unfavorable overall survival for patients with early cancer stages. Our study reveals that changes in MUC22 expression due to epigenetic alterations in NSCLC may have important biological significance and prognostic potential in LUSC when compared to LUAD. Thus, MUC22 expression and epigenetic alterations may be used for molecular subtyping of NSCLC in precision medicine.
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May-2021
Volume 45 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Lin S, Tian C, Li J, Liu B, Ma T, Chen K, Gong W, Wang JM and Huang J: Differential <em>MUC22</em> expression by epigenetic alterations in human lung squamous cell carcinoma and adenocarcinoma. Oncol Rep 45: 78, 2021
APA
Lin, S., Tian, C., Li, J., Liu, B., Ma, T., Chen, K. ... Huang, J. (2021). Differential <em>MUC22</em> expression by epigenetic alterations in human lung squamous cell carcinoma and adenocarcinoma. Oncology Reports, 45, 78. https://doi.org/10.3892/or.2021.8029
MLA
Lin, S., Tian, C., Li, J., Liu, B., Ma, T., Chen, K., Gong, W., Wang, J. M., Huang, J."Differential <em>MUC22</em> expression by epigenetic alterations in human lung squamous cell carcinoma and adenocarcinoma". Oncology Reports 45.5 (2021): 78.
Chicago
Lin, S., Tian, C., Li, J., Liu, B., Ma, T., Chen, K., Gong, W., Wang, J. M., Huang, J."Differential <em>MUC22</em> expression by epigenetic alterations in human lung squamous cell carcinoma and adenocarcinoma". Oncology Reports 45, no. 5 (2021): 78. https://doi.org/10.3892/or.2021.8029