title: miR-450b-5p Suppresses Stemness and the Development of Chemoresistance by Targeting SOX2 in Colorectal Cancer.
abstract: To investigate the role of miR-450b-5p, a newly identified microRNA, located in the Xq26 region, in development of chemoresistance in colorectal cancer (CRC), and to explore the underlying mechanism by which miR-450b-5p regulates this process. In this study, we demonstrated that expression of miR-450b-5p was downregulated in recurrent CRC tissues. We found that expression of miR-450b-5p was significantly inhibited in response to 5-fluorouracil (5-FU) treatment in HT-29 cells and HCT-116 cells. Importantly, overexpression of miR-450b-5p in 5-FU-resistant HT-29 cells reduced cell viability, but elevated DNA fragmentation levels and caspase-3 activity were induced by treatment with 5-FU. Conversely, inhibition of miR-450b-5p enhanced resistance to 5-FU, and promoted cell viability in HCT-116 cells. Mechanistically, we found that miR-450b-5p directly targeted SOX2, an essential factor in stem cells. Expression of miR-450b-5p was negatively correlated to the expression of SOX2, the percentages of CD133(+) cells present, and sphere-forming capacity in CRC cells. Finally, depletion of SOX2 abolished the effects of suppression of miR-450b-5p on stemness and chemoresistance in HT29 cells. We have demonstrated that miR-450b-5p inhibits stemness and development of chemoresistance to 5-FU in CRC cells. These results indicate that miR-450b-5p may be a key determinant of 5-FU sensitivity, and may represent a novel therapeutic target to facilitate chemotherapy for CRC.
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .
authors: Yinghu
authors: Y
authors: Jin
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .
authors: Zheng
authors: Z
authors: Jiang
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .
authors: Xu
authors: X
authors: Guan
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .
authors: Yinggang
authors: Y
authors: Chen
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .
authors: Qingchao
authors: Q
authors: Tang
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .
authors: Guiyu
authors: G
authors: Wang
authors: 1 Department of Colorectal Cancer Surgery, The Second Affiliated Hospital of Harbin Medical University , Harbin, China .|2 Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing, China .
authors: Xishan
authors: X
authors: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
chemical_list: C000589024:MIRN450 microRNA, human; D035683:MicroRNAs; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D005472:Fluorouracil