Combined Knockdown of D-dopachrome Tautomerase and Migration Inhibitory Factor Inhibits the Proliferation, Migration, and Invasion in Human Cervical Cancer.
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.



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.



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.



The inhibition of D-DT and MIF in combination may represent a potential therapeutic strategy for cervical cancer.
*Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University; and †Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai; and ‡Department of Pathology, Nantong Tumor Hospital, Nantong, China.
Qingying
Q
Wang
Yingze
Y
Wei
Jiawen
J
Zhang
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D008263:Macrophage Migration-Inhibitory Factors; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C042501:dopachrome isomerase