Open Access

Aberrant methylation‑mediated decrease of lncRNA HNF1A‑AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT

  • Authors:
    • Yewen Shi
    • Qingqing Zhang
    • Meng Xie
    • Yani Feng
    • Sijing Ma
    • Chunxi Yi
    • Zihan Wang
    • Yanju Li
    • Xiaohong Liu
    • Haiqin Liu
    • Hui Yang
    • Yan Yan
    • Yitong Zhang
    • Xiaoyong Ren
    • Huanan Luo
  • View Affiliations

  • Published online on: October 23, 2020     https://doi.org/10.3892/or.2020.7823
  • Pages: 2503-2516
  • Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aberrant methylation is one of the most frequent epigenetic alterations that regulate the expression levels of genes, including long non‑coding RNAs (lncRNAs), in tumors. However, to the best of our knowledge, the expression and function of hepatic nuclear factor 1α antisense RNA 1 (HNF1A‑AS1) and its methylation condition have not yet been reported in the development and progression of laryngeal squamous cell carcinoma (LSCC). In the present study, the expression and methylation of HNF1A‑AS1 were first examined by reverse transcription‑quantitative PCR, bisulfite genomic sequencing and methylation‑specific polymerase chain reaction in samples from patients with LSCC, which were based on the in silico analysis using The Cancer Genome Atlas data, and were then further verified in LSCC cell lines with and without 5‑Aza‑2'‑deoxycytidine (5‑Aza‑dC) treatment. Subsequently, proliferation, cell cycle distribution, migration and invasion of LSCC cells following either knockdown or overexpression of HNF1A‑AS1 were determined in vitro. Furthermore, the characteristic of HNF1A‑AS1 on epithelial‑mesenchymal transition (EMT) changes was investigated in vitro and in vivo. The associations between the expression levels of HNF1A‑AS1 and tumorigenicity and cervical lymph node metastasis were assessed in a xenograft model in nude mice. In the present study, downregulation and hypermethylation in CpG sites of HNF1A‑AS1 were detected in LSCC tissues as well as metastatic cervical lymph nodes samples when compared with those in the adjacent non‑tumor tissues. Additionally, HNF1A‑AS1 inhibited proliferation, migration and invasion of LSCC cells in vitro by regulating the process of EMT. Furthermore, HNF1A‑AS1 inhibited tumor growth and metastasis by regulating EMT in vivo. Additionally, the migration and invasion abilities, and the expression levels of HNF1A‑AS1 and EMT markers in LSCC cells were significantly reversed by treatment with 5‑Aza‑dC. In summary, HNF1A‑AS1 was downregulated by hypermethylation in LSCC and laryngeal cancer cells. These findings suggested that HNF1A‑AS1 could serve as a tumor suppressor lncRNA in LSCC by regulating the EMT process, leading to the discovery of novel therapeutic targets and strategies for the treatment of patients with LSCC.
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December-2020
Volume 44 Issue 6

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
Shi Y, Zhang Q, Xie M, Feng Y, Ma S, Yi C, Wang Z, Li Y, Liu X, Liu H, Liu H, et al: Aberrant methylation‑mediated decrease of lncRNA HNF1A‑AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT. Oncol Rep 44: 2503-2516, 2020
APA
Shi, Y., Zhang, Q., Xie, M., Feng, Y., Ma, S., Yi, C. ... Luo, H. (2020). Aberrant methylation‑mediated decrease of lncRNA HNF1A‑AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT. Oncology Reports, 44, 2503-2516. https://doi.org/10.3892/or.2020.7823
MLA
Shi, Y., Zhang, Q., Xie, M., Feng, Y., Ma, S., Yi, C., Wang, Z., Li, Y., Liu, X., Liu, H., Yang, H., Yan, Y., Zhang, Y., Ren, X., Luo, H."Aberrant methylation‑mediated decrease of lncRNA HNF1A‑AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT". Oncology Reports 44.6 (2020): 2503-2516.
Chicago
Shi, Y., Zhang, Q., Xie, M., Feng, Y., Ma, S., Yi, C., Wang, Z., Li, Y., Liu, X., Liu, H., Yang, H., Yan, Y., Zhang, Y., Ren, X., Luo, H."Aberrant methylation‑mediated decrease of lncRNA HNF1A‑AS1 contributes to malignant progression of laryngeal squamous cell carcinoma via EMT". Oncology Reports 44, no. 6 (2020): 2503-2516. https://doi.org/10.3892/or.2020.7823