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Pituitary tumor-transforming gene 1 enhances metastases of cervical cancer cells through miR-3666-regulated ZEB1

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Tumor Biology

Abstract

Early cancer metastases often occur in cervical cancer (CC) patients, resulting in poor prognosis and poor therapeutic outcome after resection of primary cancer. Hence, there is a compelling requirement for elucidating the molecular mechanisms underlying the CC cell invasiveness. Recently, the role of microRNAs (miRNAs) and pituitary tumor-transforming gene 1 (Pttg1) in the carcinogenesis of CC has been reported. Nevertheless, the relationship between miRNAs and Pttg1 remains ill-defined. Here, we showed that the levels of miR-3666 were significantly decreased and the levels of zinc finger E-box binding homeobox 1 (ZEB1) and Pttg1 were significantly increased in the CC specimens from patients, compared to the paired non-tumor tissue. Moreover, the levels of miR-3666 and ZEB1 inversely correlated. Bioinformatics analyses showed that miR-3666 targeted the 3′-untranslated region (3′-UTR) of ZEB1 messenger RNA (mRNA) to inhibit its translation, which was confirmed by luciferase reporter assay. Moreover, Pttg1 overexpression inhibited miR-3666 and subsequently increased ZEB1 and cell invasion, while Pttg1 depletion increased miR-3666 and subsequently decreased ZEB1 and cell invasion. Together, our data suggest that Pttg1 may increase CC cell metastasis, possibly through miR-3666-regulated ZEB1 levels.

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Authors and Affiliations

  1. Department of Medical Laboratory, the First Hospital of Jilin University, Changchun, 130021, China

    Lin Li & Jian-Cheng Xu

  2. Department of Obstetrics and Gynecology, the Second Hospital of Jilin University, Changchun, 130041, China

    Li-Ying Han

  3. The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, China

    Ming Yu

  4. Department of Pediatrics, the First Hospital of Jilin University, Changchun, 130021, China

    Qi Zhou

  5. Doctrine Department, Chinese Medical Schools, Changchun University of Chinese Medicine, Changchun, 130117, China

    Ping Li

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  1. Lin Li
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  2. Li-Ying Han
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  3. Ming Yu
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Correspondence to Li-Ying Han.

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Li, L., Han, LY., Yu, M. et al. Pituitary tumor-transforming gene 1 enhances metastases of cervical cancer cells through miR-3666-regulated ZEB1. Tumor Biol. 37, 15567–15573 (2016). https://doi.org/10.1007/s13277-015-4047-1

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  • DOI: https://doi.org/10.1007/s13277-015-4047-1

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