J Cancer 2018; 9(8):1394-1402. doi:10.7150/jca.23835

Research Paper

Protein arginine methyltransferase 8 gene enhances the colon cancer stem cell (CSC) function by upregulating the pluripotency transcription factor

Haishan Lin1#, Bin Wang2#, Jing Yu1, Jing Wang1, Qin Li1, Bangwei Cao1✉

1. Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
2. Department of Medical Administration, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
#There authors contributed equally to this work and should be considered co-first authors.

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Citation:
Lin H, Wang B, Yu J, Wang J, Li Q, Cao B. Protein arginine methyltransferase 8 gene enhances the colon cancer stem cell (CSC) function by upregulating the pluripotency transcription factor. J Cancer 2018; 9(8):1394-1402. doi:10.7150/jca.23835. Available from http://www.jcancer.org/v09p1394.htm

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Abstract

Objective: Cancer stem cells play a crucial role in tumor multidrug resistance and metastasis, which can produce heterogeneous tumor cells and have self-renewal ability. The related literature reported that PRMT8 was overexpressed in tumor stem cells and pluripotent stem cells. However, it's unclear how PRMT8 acts on the stemness of colon tumor cells. This study is designed to detect functions by transfecting with PRMT8 plasmid to colon cancer cells.

Methods: In this study we investigated colon cancer cell sphere and its differential expression of PRMT8 compared with colon cancer cells grown by static adherence. RKO Sphere formation assay was used to identify CSCs and verified PRMT8 and pluripotent transcription factors SOX2, OCT4, Nanog expression level in colon cell sphere. Colon cancer cell HCT-8 and RKO up-regulated PRMT8 expression by being transfected with PRMT8 plasmid to evaluate its effect on the stemness of colon tumor cell.

Results: In RKO cell sphere, stem cell surface marker CD133 and CD44 were highly expressed. And PRMT8, SOX2, OCT4 and Nanog were also highly expressed in RKO cell sphere. After PRMT8 was up-regulated in HCT-8 and RKO cells, flow cytometry proved that PRMT8 group cells have a significant increase of the side population (SP) cells with cancer stem cell surface markers CD133 and CD44. And overexpression of PRMT8 in HCT-8 and RKO cells facilitated their aggressive traits, which contained proliferation, invasion and migration, as well as leading to their drug resistance. PRMT8 may play a role in colon cancer stem cells (CSC) through its regulation of pluripotent transcription factors, such as Nanog Homeobox (Nanog), octamer-binding transcription factor-4 (Oct4) and SRY-related high-mobility-group(HMG)-box protein-2 (Sox2).

Conclusion: PRMT8 may promote the formation of colon cancer stem cells and, thus, be considered a potential therapeutic target for the treatment of malignant colon tumor.

Keywords: Protein arginine methyltransferase 8, Colon cancer stem cell, Pluripotency transcription factor