Investigation the mechanisms of SLFN5 in phthalate-induced stemness colon cancer

Abstract

Due to the changes in the diets and habit the incidence and mortality of colorectal cancer (CRC) have increased worldwide and in Taiwan The high recurrence drug-resistant-caused treatment failure and cancer metastasis are the major problems during colorectal cancer treatment Our previous study found that phthalates (DEHP/MEHP) exposure increased drug resistance in colon cancer cells The RNA microarray analysis showed that the SLFN5 is one of the genes upregulated in long term phthalates exposure In this study we tried to investigate the roles of SLFN5 in phthalates-induced stemness in CRC First the expression levels of SLFN5 were higher in DEHP/MEHP long-term treated HCT116 cells Next we established the knockdown SLFN5 cell lines by short hairpin RNA in DEHP/MEHP long-term treated HCT116 cells We found the knockdown of SLFN5 could decrease the cell stemness and the expression levels of the drug-resistant related proteins including P-glycoprotein and CD133 The tumor size were lower in the DEHP/MEHP-treated shSLFN5 HCT116 cells in xenograft models Then we found that SLFN5 translocated into nucleus in our cell systems by immunofluorescence image We further demonstrated that SLFN5 could interact with Sox2 but the mechanism was still unclear Finally we analyzed SLFN5 expression in patients’ tissues from Oncomine web and found that the expression of SLFN5 was higher in tumor part and were associated with poor survival rate of CRC patients Taken together these results suggested that SLFN5 can induce the stemness and tumorigenesis in phthalate-treated colon cancer cells For the future works we will investigate the detailed mechanisms about SLFN5 induce the cancer stemness and the interaction of SLFN5/Sox2 translocation Our findings not only understand the roles of SLFN5 mediated cancer stemness but also shed light on novel anti-cancer drug development for CRC treatment

Date of Award	2020
Original language	English
Supervisor	Chuan-Fa Chang (Supervisor)