Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer

被引：0
作者：
Binbin Xie
Bingjun Bai
Yuzi Xu
Yunlong Liu
Yiming Lv
Xing Gao
Fei Wu
Zhipeng Fang
Ying Lou
Hongming Pan
Weidong Han
机构：
[1] Zhejiang University,Department of Medical Oncology; Sir Run Run Shaw Hospital; School of Medicine
[2] Zhejiang University,Department of Colorectal Surgery; Sir Run Run Shaw Hospital; School of Medicine
[3] Zhejiang University,Department of Stomatology; Stomatology Hospital; School of Medicine
[4] Suzhou University,Department of Medical Oncology; The Second Affiliated Hospital of Suzhou University; School of Medicine
[5] Anhui University of Science and Technology,School of Medicine
来源：
Signal Transduction and Targeted Therapy | / 4卷
关键词：
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via β-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC.
引用
收藏
相关论文
共 72 条
  • [21] Orosz A(2015)Different treatment strategies and molecular features between right-sided and left-sided colon cancers World J. Gastroenterol. 21 475-490
  • [22] Fujita K(2018)Distinguishable prognostic signatures of left- and right-sided colon cancer: a study based on sequencing data Cell Physiol. Biochem. 48 476-485
  • [23] Bieberich CJ(2018)Multi-omics approach reveals distinct differences in left- and right-sided colon cancer Mol. Cancer Res. 16 374-384
  • [24] Wang X(2005)Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid GUT 54 4910-4918
  • [25] Ewing CM(2018)Posterior HOX genes and HOTAIR expression in the proximal and distal colon cancer pathogenesis J. Transl. Med. 16 988-994
  • [26] Sui BQ(2010)HOXB13, a target of DNMT3B, is methylated at an upstream CpG island, and functions as a tumor suppressor in primary colorectal tumors PLoS ONE 5 1188-1201
  • [27] Zhang CD(2014)Proteomic and functional investigation of the colon cancer relapse-associated genes NOX4 and ITGA3 J. Proteome Res. 13 2553-2560
  • [28] Liu JC(2016)Location of primary tumor and benefit from anti-epidermal growth factor receptor monoclonal antibodies in patients with RAS and BRAF wild-type metastatic colorectal cancer Oncologist 21 8541-8546
  • [29] Wang L(2018)Clinical, pathological, and molecular characteristics of CpG island methylator phenotype in colorectal cancer: a systematic review and meta-analysis Transl. Oncol. 11 145-154
  • [30] Dai DQ(2012)Association between methylation in mismatch repair genes, V600E BRAF mutation and microsatellite instability in colorectal cancer patients Mol. Biol. Rep. 39 2314-2327
12345678