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Combined Knockdown of D-dopachrome Tautomerase and Migration Inhibitory Factor Inhibits the Proliferation, Migration, and Invasion in Human Cervical Cancer
  1. Qingying Wang, MD*,
  2. Yingze Wei, MD, and
  3. Jiawen Zhang, MD*
  1. * Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University; and
  2. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai; and
  3. Department of Pathology, Nantong Tumor Hospital, Nantong, China.
  1. Address correspondence and reprint requests to Jiawen Zhang, MD, Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University, No 301 Yanchang Middle Rd, Shanghai 200072, China. E-mail: jwzhang929{at}


Objective D-dopachrome tautomerase (D-DT) is a homologue of macrophage migration inhibitory factor (MIF) with similar functions. However, the possible biological roles of D-DT in cervical cancer remain unknown so far.

Methods D-dopachrome tautomerase was assessed by immunohistochemistry in 83 cervical cancer and 31 normal cervix tissues. The stable knockdown of D-DT and MIF by lentivirus-delivered short hairpin RNA was established, and tumor growth was examined in vitro and in vivo. The effects of D-DT and MIF on the migration and invasion were further detected by wound healing assay and transwell assay. Western blot was used to explore the mechanism of D-DT and MIF in cervical cancer pathogenesis.

Results We found that D-DT was significantly high in cervical cancer, which correlated with lymph node metastasis. The knockdown of D-DT and MIF, individually and additively, inhibited the proliferation, migration, and invasion in HeLa and SiHa cells and restrained the growth of xenograft tumor. The ablation of D-DT and MIF rescued the expression of E-cadherin and inhibited the expression of PCNA, cyclin D1, gankyrin, Sam68, and vimentin, as well as phospho-Akt and phospho-glycogen synthase kinase 3-β.

Conclusions The inhibition of D-DT and MIF in combination may represent a potential therapeutic strategy for cervical cancer.

  • Cervical cancer
  • D-dopachrome tautomerase
  • Macrophage migration inhibitory factor

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  • The authors declare no conflicts of interest.