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Serine 727 phosphorylation is necessary to induce the STAT3-mediated transcription of LINC00184 in oesophageal squamous cell carcinoma

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Abstract

LINC00184 has been suggested to be associated with cancer prognosis and has been implicated in cancer glycolysis; however, its role in oesophageal squamous cell carcinoma (ESCC) remains poorly understood. Herein, to understand the expression and the biological roles of LINC00184 in ESCC, in situ hybridization (ISH) and quantitative PCR (qPCR) were performed to detect the expression of LINC00184 in tissue blocks and in fresh tissues, respectively. Furthermore, with an in vitro cell culture system, LINC00184 was stably knocked down in ESCC cell lines KYSE-150 and Eca109, followed by determining alterations in their proliferation and motility relative to control. To gain insight into the regulation of LINC00184, STAT3 was bioinformatically identified as a transcription factor of LINC00184, which was further corroborated by chromatin-immunoprecipitation (CHIP) assay. The dephosphorylation of STAT3 with NSC74859 was shown to be unable to suppress the expression of LINC00184 in vivo in a xenograft mouse model. Moreover, STAT3, once phosphorylated at serine 727, tended to translocate into the mitochondria to promote LINC00184 expression in ESCC cells. Together, these data strongly support the oncogenic role of LINC00184 in ESCC.

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Data availability

The datasets analyzed in this study are available in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public repository.

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Funding

This work was supported by the National Science Foundation of China (Grant No. 82073084).

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Authors

Contributions

YX and SLL were the principal investigators who designed and conceived the study and obtained financial support. CLJ and HQ analyzed the data and wrote the manuscript. CLJ and HQ prepared the dataset. All authors have read, revised, and approved the final manuscript.

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Correspondence to Yue Xu or Shenglei Li.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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This research project was approved by the Ethics Committee of Peking Union Medical College Hospital. Written consents were obtained from each patient.

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Jin, C., Qi, H., Xu, Y. et al. Serine 727 phosphorylation is necessary to induce the STAT3-mediated transcription of LINC00184 in oesophageal squamous cell carcinoma. Mol Cell Biochem 477, 1775–1787 (2022). https://doi.org/10.1007/s11010-022-04405-4

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