Hypermethylation of the RSK4 promoter associated with BRAF V600E promotes papillary thyroid carcinoma

  • Authors:
    • Yanan Yin
    • Kui Che
    • Jianxia Hu
    • Hui Hua
    • Anbing Dong
    • Jueru Wang
    • Jiarui Yu
    • Qing Zhang
    • Shihua Zhao
    • Yuhang Zhao
    • Ping Wang
    • Fei Wang
    • Yangang Wang
    • Jingwei Chi
    • Wenhai Sun
  • View Affiliations

  • Published online on: February 25, 2020     https://doi.org/10.3892/ijo.2020.4999
  • Pages: 1284-1293
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Abstract

Ribosomal S6 kinase 4 (RSK4) is a putative tumor suppressor gene which is inactivated by epigenetic events in a number human malignancies; however, its role in papillary thyroid carcinoma (PTC) remains largely unknown. The aim of this study was to explore the methylation status of the RSK4 promoter in PTC, and to determine its potential role in thyroid carcinogenesis. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analyses were performed to examine the RSK4 mRNA and protein levels, respectively. Methylation‑specific PCR (MSP) and bisulfite genomic sequencing (BGS) were used to analyze methylation status of the RSK4 gene. Sanger sequencing was further carried out to detect the BRAF V600E mutation. Cell proliferation assay was finally performed to evaluate the role of hypermethylation in the growth of PTC cells. The association between RSK4 methylation and the clinicopathological characteristics of patients with PTC was assessed. The methylation frequency of the RSK4 promoter in PTC tissues was higher than that in paired paracancerous tissues. Coincidentally, the RSK4 mRNA levels were also downregulated in PTC tissues when compared with the paracancerous counterparts. The hypermethylation of RSK4 was associated with tumor size and lymph node metastasis. Furthermore, the BRAF V600E mutation may influence RSK4 expression and methylation. Moreover, RSK4 hypermethylation was observed in thyroid cancer cell lines, which was consistent with a lack of RSK4 expression. Upon the 5‑Aza‑deoxycytidine treatment of thyroid cancer cells, RSK4 expression was significantly upregulated, while cell proliferation was inhibited. On the whole, the findings of the present study demonstrate that the hypermethylation of the RSK4 promoter may be one of the mechanisms responsible for the poor RSK4 expression in PTC. Thus, these data suggest that RSK4 may serve as a molecular target for the early diagnosis and treatment of PTC.

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May 2020
Volume 56 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Yin, Y., Che, K., Hu, J., Hua, H., Dong, A., Wang, J. ... Sun, W. (2020). Hypermethylation of the RSK4 promoter associated with BRAF V600E promotes papillary thyroid carcinoma. International Journal of Oncology, 56, 1284-1293. https://doi.org/10.3892/ijo.2020.4999
MLA
Yin, Y., Che, K., Hu, J., Hua, H., Dong, A., Wang, J., Yu, J., Zhang, Q., Zhao, S., Zhao, Y., Wang, P., Wang, F., Wang, Y., Chi, J., Sun, W."Hypermethylation of the RSK4 promoter associated with BRAF V600E promotes papillary thyroid carcinoma". International Journal of Oncology 56.5 (2020): 1284-1293.
Chicago
Yin, Y., Che, K., Hu, J., Hua, H., Dong, A., Wang, J., Yu, J., Zhang, Q., Zhao, S., Zhao, Y., Wang, P., Wang, F., Wang, Y., Chi, J., Sun, W."Hypermethylation of the RSK4 promoter associated with BRAF V600E promotes papillary thyroid carcinoma". International Journal of Oncology 56, no. 5 (2020): 1284-1293. https://doi.org/10.3892/ijo.2020.4999