Oncotarget

Research Papers:

The role and gene expression profile of SOCS3 in colorectal carcinoma

Xing Dong, Jing Wang, Bo Tang, Yeng-Xue Hao, Ping-Yang Li, Shi-Yong Li and Pei-Wu Yu _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:15984-15996. https://doi.org/10.18632/oncotarget.23477

Metrics: PDF 853 views  |   HTML 1283 views  |   ?  


Abstract

Xing Dong1,2, Jing Wang3, Bo Tang1, Yeng-Xue Hao1, Ping-Yang Li1, Shi-Yong Li2 and Pei-Wu Yu1

1Department of General Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China

2Department of General Surgery, PLA Army General Hospital, Beijing, China

3Department of Obstetrics and Gynecology, PLA Army General Hospital, Beijing, China

Correspondence to:

Pei-Wu Yu, email: yupeiwu01@sina.com

Keywords: SOCS3; colorectal carcinoma; mechanisms; indicator; gene therapy

Received: September 12, 2017     Accepted: December 04, 2017     Epub: December 20, 2017     Published: March 23, 2018

ABSTRACT

SOCS3 has been postulated to play a role in the occurrence and progression of malignancies. However, the relationship of SOCS3 with colorectal carcinoma remains poorly understood. The purpose of the study was to explore the role of SOCS3 in colorectal carcinoma and its underlying mechanisms. Protein and mRNA expression of SOCS3 in colorectal carcinoma and normal colorectal mucosa was detected using immunohistochemistry and real-time quantitative PCR. SOCS3 expression was significantly lower in colorectal carcinoma tissue than in normal colorectal mucosa, and was negatively correlated with tumor invasion depth, lymph node metastasis, differentiation degree, and TNM stage. A stably transfected colorectal carcinoma cell line (8348SOCS3) with high expression of SOCS3 was established. The effects of SOCS3 overexpression on the growth, proliferation, invasion and tumor formation of colorectal carcinoma cells were examined by CCK-8 assay, transwell method and tumorigenicity assays in nude mice. Then we found SOCS3 overexpression significantly decreased proliferation and invasion capability of 8348 cells in vitro and in vivo. Furthermore, the effect of SOCS3 overexpression on the gene expression profile of colorectal carcinoma cells was analyzed using human genome arrays. The results revealed 369 genes that were differentially expressed in 8348SOCS3 cells. 193 genes was significantly increased and 176 genes was significantly decreased. Bioinformatics analysis demonstrated that high SOCS3 expression affected multiple signaling pathways in colorectal carcinoma including TGF-β/Smads, NF-κB, and HIF-MAPK pathways. Especially for the TGF-β/Smads pathways, high SOCS3 expression could inhibit TGF-β1 expression and activate Smad4 expression. These data suggested that low expression of SOCS3 was associated with the occurrence and progression of colorectal carcinoma. SOCS3 protein may be a useful indicator for malignancy and prognosis of colorectal carcinoma and also a new target for gene therapy.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 23477