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Overexpression of Cullin4A correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma

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Abstract

Background

Cullin4A (CUL4A), which is a component of E3 ubiquitin ligase, is implicated in many cellular events. Although the altered expression of CUL4A has been reported in several human cancers, the role of CUL4A in esophageal cancer remains unknown.

Methods

We investigated the CUL4A expression in primary esophageal squamous cell carcinoma (ESCC) tissue specimens from 120 patients by immunohistochemistry and explored its clinical relevance and prognostic value. Furthermore, the effect of the expression of CUL4A on cancer cell proliferation was analyzed in vitro using an siRNA silencing technique.

Results

The higher expression of CUL4A was significantly associated with a deeper depth of tumor invasion (P < 0.001) and the presence of venous invasion (P = 0.014). The disease-specific survival (DSS) rate in patients with tumors that showed high CUL4A expression levels was significantly lower than that in patients whose tumors showed low CUL4A expression levels (P = 0.001). Importantly, the CUL4A status was identified as an independent prognostic factor for DSS (P = 0.045). Our results suggested that the CUL4A expression has significant prognostic value in ESCC. Furthermore, CUL4A gene silencing significantly inhibited the proliferation of ESCC cells in vitro. In addition, the knockdown of the CUL4A expression induced G1 phase arrest and increased the p21 and p27 protein levels.

Conclusions

CUL4A might play an important role in regulating the proliferation of ESCC cells and promoting the development of postoperative recurrence.

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Authors and Affiliations

  1. Department of Surgery, Nara Medical University, 840 Shijo-Cho, Kashihara, Nara, 634-8521, Japan

    Hiroshi Nakade, Kazuhiro Migita, Sohei Matsumoto, Kohei Wakatsuki, Tomohiro Kunishige, Shintaro Miyao & Masayuki Sho

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  1. Hiroshi Nakade
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  2. Kazuhiro Migita
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  3. Sohei Matsumoto
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  4. Kohei Wakatsuki
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  5. Tomohiro Kunishige
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  6. Shintaro Miyao
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  7. Masayuki Sho
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Correspondence to Hiroshi Nakade.

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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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Nakade, H., Migita, K., Matsumoto, S. et al. Overexpression of Cullin4A correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma. Int J Clin Oncol 25, 446–455 (2020). https://doi.org/10.1007/s10147-019-01547-2

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  • DOI: https://doi.org/10.1007/s10147-019-01547-2

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