title: miR-659-3p is involved in the regulation of the chemotherapy response of colorectal cancer via modulating the expression of SPHK1.
abstract: Colorectal cancer (CRC) is one of most prevalent malignant diseases worldwide. Metastasis and chemo-resistance are the two prominent death-related factors of CRCs. Thus, it is urgent to understand the mechanism responsible for the chemo-resistant properties of CRC and develop new therapeutic methods. Here, we found that the expression of miR-659-3p was significantly reduced in cisplatin (CDDP)-resistant HT29 and LOVO colorectal cancer cells and in CDDP-resistant clinical colorectal cancer samples compared with respective CDDP-sensitive counterparts. Sphingosine kinase 1 (SPHK1) is a direct target of miR-659-3p in colorectal cancer cells, and it is negatively regulated by miR-659-3p. We found that anti-miR-659-3p could increase the IC50 of CDDP in parental HT29 and LOVO colorectal cancer cells; additionally, miR-659-3p mimics decreased the IC50 of CDDP in HT29/CDDP and LOVO/CDDP colorectal cancer cells. Furthermore, we showed that the miR-659-3p/SPHK1 pathway was involved in the regulation of chemotherapy responses of colorectal cancer cells in vivo. In all, our findings suggest a new mechanism involved in the regulation of the chemotherapy response of CRC and might provide new targets for CRC prevention and treatment.
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center Tianjin 300121, P. R. China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, The First Hospital of Jiaxing Zhejiang 314000, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center Tianjin 300121, P. R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qin
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center Tianjin 300121, P. R. China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Fu
authors.affiliation: Department of Colorectal Surgery, Tianjin Union Medical Center Tianjin 300121, P. R. China.
authors.forename: Xipeng
authors.initials: X
authors.lastname: Zhang
keywords: CDDP; CRC; SPHK1; cisplatin; colorectal cancer; miR-659-3p