Tumor Biology

, Volume 37, Issue 9, pp 12477–12483 | Cite as

Epigenetic silencing of TPM2 contributes to colorectal cancer progression upon RhoA activation

  • Ji Cui
  • Yonghua Cai
  • Ying Hu
  • Zenghong Huang
  • Yanxin Luo
  • Andrew M. Kaz
  • Zihuan Yang
  • Dianke Chen
  • Xinjuan Fan
  • William M. Grady
  • Jianping Wang
Original Article

Abstract

Beta-tropomyosin (β-tropomyosin, TPM2) has been found to be downregulated in colorectal cancer (CRC) in previous studies. In this study, we aimed to investigate the mechanisms and potential biological consequences of the downregulation of TPM2 in colorectal cancer. TPM2 expression in colorectal cancer was assessed by qRT-PCR and immunostaining. The biological functions of TPM2 were assessed in cell lines either overexpressing or underexpressingTPM2. Aberrant DNA methylation in the promoter region is associated with suppression of TPM2 expression in primary colorectal cancer tissue samples. Treatment with the demethylation agent 5-AZA can induceTPM2 expression in colorectal cancer cell lines. Reconstitution of TPM2 suppresses cell proliferation and migration in colorectal cancer cell lines, whereas the loss of TPM2 expression is associated with increased tumor proliferation and migration in vitro, which was accompanied by RhoA activation. In summary, our findings indicate that TPM2 appears to be commonly silenced by aberrant DNA methylation in colon cancer. TPM2 loss is associated with RhoA activation and tumor proliferation.

Keywords

Colorectal cancer DNA methylation TPM2 

Notes

Acknowledgments

Support for these studies was provided by a National Basic Research Program of China (973 Program) (No. 2015CB554001, JW), Program of Introducing Talents of Discipline to Universities of China (B12003, JW) and International Science & Technology Cooperation Program of China (2011DFA32570, JW), the Science and Technology Program of Guangzhou (No. 201506010099, YL; No. 2014Y2-00160, JW), National Natural Science Foundation of China (81172040 JW;81201920 and 81472257, YL), the Guangdong Natural Science Funds for Distinguished Young Scholars (2016A030306002, YL), and the Fundamental Research Funds for the Central Universities (Sun Yat-sen University) (No. 2015ykzd10, YL; No. 13ykpy37, YL).

Conflicts of interest

No conflicts of interest exist for any of the authors.

Authors’ contributions

JC and YC carried out the molecular genetic studies, participated in the sequence alignment, and drafted the manuscript. YH, ZH, YL, and AMK carried out the immunoassays and drafted the manuscript. DC, ZY, and XF participated in the design of the study and performed the statistical analysis. WMG and JW conceived of the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Ji Cui
    • 1
  • Yonghua Cai
    • 2
    • 3
  • Ying Hu
    • 4
  • Zenghong Huang
    • 2
    • 3
  • Yanxin Luo
    • 2
    • 3
    • 7
  • Andrew M. Kaz
    • 7
    • 8
    • 9
  • Zihuan Yang
    • 3
  • Dianke Chen
    • 3
    • 5
  • Xinjuan Fan
    • 3
    • 6
  • William M. Grady
    • 7
    • 8
  • Jianping Wang
    • 2
    • 3
  1. 1.Department of Gastrointestinal Surgerythe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  2. 2.Department of Colorectal Surgerythe Sixth Affilated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  3. 3.Gastrointestinal InstituteSun Yat-Sen UniversityGuangzhouChina
  4. 4.Department of Medicine IIthe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  5. 5.Department of Oncologythe Sixth Affilated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  6. 6.Department of Pathologythe Sixth Affilated Hospital of Sun Yat-Sen UniversityGuangzhouChina
  7. 7.Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleUSA
  8. 8.Department of MedicineUniversity of Washington School of MedicineSeattleUSA
  9. 9.Research and Development ServiceVA Puget Sound Health Care SystemSeattleUSA

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