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miR-4306 Suppresses Proliferation of Esophageal Squamous Cell Carcinoma Cell by Targeting SIX3

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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers and the primary cause of cancer-related mortality in China. micoRNA plays a vital role during tumor initiation and malignant progression. miR-4306 has been reported to negatively regulate aggressive cell phenotypes in triple-negative breast cancer (TNBC). Nevertheless, the function of miR-4306 in ESCC was still not clear. In this study, we detected miR-4306 expression by quantitative real-time reverse transcription-PCR (qRT-PCR) and found that miR-4306 expression was downregulated in human ESCC tissue samples and cell lines. Moreover, miR-4306 overexpression could restrain ESCC cell proliferation, migratory and invasive ability and epithelial-mesenchymal transition (EMT), promote cell apoptosis after treatment with or without cisplatin. In contrast, inhibiting the expression of miR-4306 showed the opposing results. Furthermore, we explored the molecular mechanism of effects of miR-4306 and found that miR-4306 inhibited the expression of SIX3 by interaction with SIX3 3′UTR in ESCC cells, and SIX3 overexpression significantly reversed the effect of miR-4306-mediated ESCC cells proliferation. The current study provided evidence of miR-4306 as a tumor suppression gene in ESCC.

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Fig. 1: miR-4306 expression was declined in ESCC tissues and cell lines.
Fig. 2: Upregulation of miR-4306 expression inhibited ESCC cell growth and colony formation.
Fig. 3: miR-4306 promoted ESCC cell apoptosis after treatment with or without cisplatin.
Fig. 4: miR-4306 suppressed ESCC cell migratory and invasive ability.
Fig. 5: miR-4306 regulated SIX3 expression by targeting the 3′-UTR.
Fig. 6: The effect of miR-4306 on the proliferation of ESCC cells was partially rescued by the re-expression of SIX3.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China [grant no. 81872398], the Natural Science Foundation of Shanxi Province, China [grant no. 201901D111214] and the Open Fund from Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, China [grant no. KLMC/SXMU-201906].

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Author notes

  1. These authors contributed equally: Chengyuan Yang, Zichan Guo

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Chengyuan Yang, Zichan Guo, Yuan Wei & Xiaoxia Wang

  2. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Zitong Zhao & Yongmei Song

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  1. Chengyuan Yang
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  2. Zichan Guo
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Contributions

Xiaoxia Wang and Yongmei Song conceived and designed the experiments. Chengyuan Yang and Zichan Guo performed the experiments. Chengyuan Yang, Zichan Guo, Zitong Zhao, and Yuan Wei analyzed the data and generated the figures. Zichan Guo and Xiaoxia Wang wrote the manuscript. All authors gave final approval for the submitted version.

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Correspondence to Xiaoxia Wang or Yongmei Song.

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The authors declare no competing interests.

Ethical Approval

The study protocol was approved by the Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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All participants in this study were informed and gave a written consent.

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Yang, C., Guo, Z., Zhao, Z. et al. miR-4306 Suppresses Proliferation of Esophageal Squamous Cell Carcinoma Cell by Targeting SIX3. Cell Biochem Biophys 79, 769–779 (2021). https://doi.org/10.1007/s12013-021-00994-x

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