AUTHOR=Lin Qi , Li Jun , Zhu Dexiang , Niu Zhengchuan , Pan Xiangou , Xu Pingping , Ji Meiling , Wei Ye , Xu Jianmin 

TITLE=Aberrant Scinderin Expression Correlates With Liver Metastasis and Poor Prognosis in Colorectal Cancer

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01183

DOI=10.3389/fphar.2019.01183

ISSN=1663-9812

ABSTRACT=<p>Many genes and mutations have been reported for colorectal cancer (CRC); however, very few have been associated with colorectal cancer liver metastasis (CRLM). We performed gene expression profiling experiments to identify genetic markers for CRLM and elucidate the molecular mechanisms. Microarray experiments were performed on CRC primary tumor samples with or without liver metastasis (LM) using the Affymetrix U133 plus 2.0 GeneChip Array. A new identified gene-scinderin (<italic>SCIN</italic>) was overexpressed with synchronous LM at both the RNA level evaluated with quantitative real-time PCR and protein level evaluated with immunohistochemistry and also with short overall survival analyzed with Kaplan-Meier method. With multivariate analysis indicated that <italic>SCIN</italic> served as an independent poor prognostic predictor for CRC patients. Disease-free survival was also significantly lower in <italic>SCIN</italic> overexpressing CRC patients with metachronous LM. In addition, <italic>SCIN</italic> knockdown significantly reduced cell proliferation, induced cell cycle arrest, and promoted the expression of some cell cycle apoptosis-related protein. Moreover, the <italic>DIAPH1</italic>, <italic>STAT3</italic>, <italic>CDK2</italic>, <italic>CDK4</italic>, and <italic>EGFR</italic> levels were downregulated, whereas <italic>CDKN2B</italic> and <italic>COL4A1</italic> were upregulated in DLD-1-shSCIN cells by microarray analysis compared with DLD-1 shCon cells. These findings revealed that <italic>SCIN</italic> may serve as an important predictor of CRLM and poor outcome for CRC patients. <italic>SCIN</italic> may be a potential therapeutic target in human CRC. However, translation of its roles into clinical practice will require further investigation and additional experimental validation.</p>