Ubiquitin C-terminal hydrolase L1 promotes lymph node metastasis in small cell neuroendocrine carcinomas of the cervix

泛素 C 端水解酶 L1 促进宫颈小细胞神经内分泌癌淋巴结转移

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作者:Yunqiang Zhang, Jingxin Ding, Xuyin Zhang, Keqin Hua

Conclusion

UCHL1 is a potential biomarker of LNM in SCNEC. UCHL1 might promote SCNEC cell migration and invasion by reducing PROX1 ubiquitination.

Methods

Differentially expressed genes in SCNEC compared with squamous cell carcinoma (SCC) and adenocarcinoma (AC) were screened by microarray and immunohistochemical analyses. The biological functions of the identified genes were examined in a SCNEC cell line using RNA interference and over-expression plasmid-transfection technologies. Co-expression network analysis and immunoprecipitation technology were used to explore the potential mechanisms.

Objective

To screen for specific differentially expressed genes in small cell neuroendocrine carcinoma of the cervix (SCNEC) and to further explore their roles and mechanisms in tumor progression.

Results

Compared with SCC and AC, UCHL1 (encoding ubiquitin C-terminal hydrolase L1) was identified as a specific differentially expressed gene in SCNEC, which was positively related to lymph node metastasis (LNM). Migration and invasion of SCNEC tumor cells were induced by UCHL1 over-expression and suppressed by UCHL1 down-regulation, as shown by scratch and transwell invasion assays. Co-expression network analysis suggested that Prospero homeobox protein 1 (PROX1) might interact with UCHL1, and in vivo immunoprecipitation and western blots verified that levels of ubiquitinated PROX1 were significantly decreased following UCHL1 overexpression.

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