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      Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression

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          Abstract

          The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m 2 fluorouracil, 200 mg/m 2 leucovorin and 85 mg/m 2 oxaliplatin). In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m 2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m 2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m 2 and 44 h continuous intravenous infusion of 1,200 mg/m 2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P<0.05). The miR-196 mRNA was significantly correlated with lymph node metastasis, tumor stage and distant metastasis (P<0.05). miR-196 was indicated to be negatively correlated with HoxB8 mRNA expression (r=−0.458; P<0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of patients was 0.949±0.691, which was increased compared with the chemotherapy-resistant group (0.345±0.536; P<0.01). The relative level of HoxB8 mRNA in the chemotherapy-sensitive group was 0.490±0.372, which was decreaesd compared with the chemotherapy-resistant group (0.725±0.438; P<0.05). HoxB8 protein expression level in the chemotherapy-sensitive group was decreased compared with the chemotherapy-resistant group (Z=−2.396; P=0.017). Overall, miR-196 was correlated with metastasis and prognosis, and HoxB8 was highly expressed in CRC tissues. The difference in the gene expression of miR-196 and HoxB8 may be associated with the sensitivity to FOLFOX4 for CRC patients. In addition, the highly expressed miR-196 increased the sensitivity of CRC cells to chemotherapy with FOLFOX4 by inhibiting HoxB8.

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          Author and article information

          Journal
          Oncol Lett
          Oncol Lett
          OL
          Oncology Letters
          D.A. Spandidos
          1792-1074
          1792-1082
          November 2016
          29 September 2016
          29 September 2016
          : 12
          : 5
          : 4041-4047
          Affiliations
          [1 ]Department of Medical Oncology, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
          [2 ]Fujian Medical University Stem Cell Research Institute, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
          [3 ]Fujian Key Laboratory of Translational Cancer Medicine, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
          [4 ]Department of Colorectal Surgery, Union Hospital, Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
          Author notes
          Correspondence to: Dr Xingrong Lu, Department of Colorectal Surgery, Union Hospital, Fujian Medical University, 29 Xinquan Road, Fuzhou, Fujian 350001, P.R. China, E-mail: xingronglu2014@ 123456163.com
          Article
          PMC5104229 PMC5104229 5104229 OL-0-0-5210
          10.3892/ol.2016.5210
          5104229
          27895768
          afc6fbf6-65d5-45d0-98c2-c42d01b49670
          Copyright © 2016, Spandidos Publications
          History
          : 10 February 2015
          : 03 March 2016
          Categories
          Articles

          FOLFOX4,miR-196,homeobox B8,colorectal cancer,neoadjuvant chemotherapy

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