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MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma

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Abstract

Recently, microRNA-99 family members, such as miR-99a/b and miR-100, have been reported to exhibit abnormal expression in various malignant tumors, but their functions in carcinomas are controversial. In this study, we focused on miR-99a and miR-100, which were determined to be universally downregulated in esophageal squamous cell carcinoma, and investigated their functions and potential mechanisms of action. The downregulation of miR-99a/100 was validated by qRT-PCR in 101 ESCC surgical tissue samples and in 3 ESCC cell lines. The overexpression of miR-99a and miR-100 via the transient transfection of the corresponding precursor molecules inhibited cell proliferation by inducing apoptosis in the ESCC cell lines. To investigate the molecular mechanism of miR-99a/100-induced apoptosis, luciferase reporter assays and Western blots were performed to demonstrate that the overexpression of miR-99a/100 suppressed the expression of mTOR by directly targeting its 3′UTR in a post-transcriptional manner. Clinically, the decreased expression of miR-99a/100 was associated with worse overall survival in ESCC patients. In conclusion, these results indicated that miR-99a and miR-100 inhibited cell proliferation by suppressing mTOR in ESCC cell lines, and therefore, the miR-99a/100-mTOR signaling pathway is a potential therapeutic target for inducing apoptosis to combat ESCC.

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Acknowledgments

This study was supported by the Chinese National Natural Science Foundation Grants 30971463 and 81172336, the International Science and Technology Corporation and Exchange Project Grant 2010DFB30650, the Key Technologies R & D Program Grants 2012AA02A502, 2012AA02A503 and 2012AA02A207, and the Doctoral Fund of Ministry of Education of China Grant 20091106110031.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing, 100021, People’s Republic of China

    Jian Sun, Zhaoli Chen, Xiaogang Tan, Fang Zhou, Fengwei Tan, Yibo Gao, Nan Sun, Xiaohui Xu, Kang Shao & Jie He

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  1. Jian Sun
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  2. Zhaoli Chen
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  3. Xiaogang Tan
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  4. Fang Zhou
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  7. Nan Sun
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  9. Kang Shao
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  10. Jie He
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Correspondence to Jie He.

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Sun, J., Chen, Z., Tan, X. et al. MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma. Med Oncol 30, 411 (2013). https://doi.org/10.1007/s12032-012-0411-9

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  • DOI: https://doi.org/10.1007/s12032-012-0411-9

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