title: HuD promotes progression of oral squamous cell carcinoma.
abstract: Head and neck cancer, including oral squamous cell carcinoma (OSCC), ranks as the sixth most common malignancy worldwide. Overall 5-year survival rates of OSCC have not significantly improved during the past 3 decades and the 5-year survival rate is less than 50%. Several invasion grading systems have been employed in OSCC, however, their utility is still controversial. HuD belongs to the Hu protein family and acts as an RNA-binding protein involved in mRNA stability and translational regulation. Although HuD has a pivotal role for neuronal differentiation, the functional role of HuD in OSCCs is still unclear. In this study, we examined HuD expression in 82 OSCC cases. Expression of HuD was observed in 36.6% of OSCCs and significantly associated with histological differentiation, nodal metastasis and mode of invasion. HuD expression in high-metastatic HSC3 cells was higher than in low-metastatic HSC4 cells, and inhibition of invasion ability and activation of caspase-3 were shown by HuD siRNA-treated HSC3 cells. Furthermore, we clarified that HuD regulates expression of vascular endothelial growth factor (VEGF)-A, VEGF-D, matrix metallopeptidase (MMP)-2 and MMP-9. These results suggest that HuD is a useful diagnostic and therapeutic target in OSCCs.
authors.affiliation: Department of Molecular Pathology, Nara Medical University, Kashihara, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Sasahira
authors.forename: Miyako
authors.initials: M
authors.lastname: Kurihara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ueda
authors.forename: Chie
authors.initials: C
authors.lastname: Nakashima
authors.forename: Sayako
authors.initials: S
authors.lastname: Matsushima
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Kirita
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D018450:Disease Progression; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism*; D000067779:ELAV-Like Protein 4; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D051959:ELAV Proteins; D000067779:ELAV-Like Protein 4; C498010:ELAVL4 protein, human; D034741:RNA, Small Interfering