HMGB3 promotes growth and migration in colorectal cancer by regulating WNT/β-catenin pathway

PLoS One. 2017 Jul 5;12(7):e0179741. doi: 10.1371/journal.pone.0179741. eCollection 2017.

Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths and a major health problem. High mobility group box 3 (HMGB3), a member of the high-mobility group box (HMGB) family, was reported to be over-expressed in gastric carcinoma and bladder cancer. However, the function of HMGB3 in CRC remains unclear. Here, we found that HMGB3 was up-regulated in CRC at both mRNA and protein levels. qRT-PCR results showed that high expression of HMGB3 had positive correlation with serosal invasion, lymph metastasis, and tumor-node-metastasis (TNM) stage in CRC patient. Functional experiments showed that HMGB3 can promote CRC cells proliferation and migration in vitro. Moreover, we found HMGB3 can active WNT/β-catenin pathway to increase the expression level of c-Myc and MMP7. These results may be the reason for HMGB3 oncogene role in CRC. In summary, our data indicated that HMGB3 may serve as an oncoprotein and could be used as a potential prognostic marker in CRC.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Colon / metabolism
  • Colon / pathology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • HMGB3 Protein / physiology*
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Wnt Signaling Pathway*

Substances

  • HMGB3 Protein

Grants and funding

This work was supported by National Natural Science Foundation of China (http://www.nsfc.gov.cn/, No. 81672429 to XNL and No. 81502479 to YXL). XNL designed the experiments and YXL prepared the manuscript.