Elevated Expression of ASXL2 is Associated with Poor Prognosis in Colorectal Cancer by Enhancing Tumorigenesis and Inducing Cell Proliferation

Ran Cui; Ludi Yang; Yiwei Wang; Ming Zhong; Minhao Yu; Bo Chen

doi:10.2147/CMAR.S266083

Elevated Expression of ASXL2 is Associated with Poor Prognosis in Colorectal Cancer by Enhancing Tumorigenesis and Inducing Cell Proliferation

Cancer Manag Res. 2020 Oct 19:12:10221-10228. doi: 10.2147/CMAR.S266083. eCollection 2020.

Authors

Ran Cui^#¹, Ludi Yang^#², Yiwei Wang^#², Ming Zhong³, Minhao Yu³, Bo Chen¹

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, East Hospital Affiliated Tongji University, Tongji University School of Medicine, Shanghai 200120, People's Republic of China.
² State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
³ Department of Gastrointestinal Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People's Republic of China.

^# Contributed equally.

Abstract

Objective: Colorectal cancer is one of the most common malignant tumors worldwide. ASXL2 is an enhancer of the trithorax and polycomb genes, which have been proven to act in many tumor types. The role of ASXL2 in the occurrence and development of tumors has been extensively studied in recent years. However, the relationship between ASXL2 and the prognosis of CRC is still unclear.

Materials and methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and immunohistochemistry (IHC) were used to examine the expression of ASXL2 in CRC tissues. Cells were transfected with siRNAs or lentivirus to regulate the expression of ASXL2. The effects of ASXL2 on the proliferation of CRC cells were determined by CCK8 assay.

Results: This study demonstrated that ASXL2 was significantly more highly expressed in CRC specimens than in normal adjacent tissues. The upregulation of ASXL2 was related to advanced clinical stage. Patients who exhibited high expression levels of ASXL2 had poorer overall survival, whereas those with low expression of ASXL2 survived longer. Multivariate Cox regression analysis revealed that ASXL2 expression could be considered an independent prognostic factor for CRC. Inhibition or overexpression of ASXL2 markedly influenced the proliferation of CRC cells.

Conclusion: These results showed that ASXL2 could induce cell proliferation, which was associated with poor prognosis of CRC patients, suggesting that ASXL2 might be a new therapeutic target for CRC.

Keywords: ASXL2; cell proliferation; colorectal cancer; prognosis marker.

Grants and funding

This work was supported by the grant from the National Natural Science Foundation of China (No. 81702300), The Outstanding Clinical Discipline Project of Shanghai Pudong (No. PWYgy2018-02) and The Research project of Shanghai Municipal Health Commission (No. 20204Y0302).