TY - JOUR T1 - Development of a Novel Oncolytic Adenovirus Expressing a Short-hairpin RNA Against Cullin 4A JF - Anticancer Research JO - Anticancer Res SP - 161 LP - 168 DO - 10.21873/anticanres.13937 VL - 40 IS - 1 AU - KEISAKU WAKABAYASHI AU - FUMINORI SAKURAI AU - RYOSUKE ONO AU - TOSHIYOSHI FUJIWARA AU - HIROYUKI MIZUGUCHI Y1 - 2020/01/01 UR - http://ar.iiarjournals.org/content/40/1/161.abstract N2 - Background: Arming of an oncolytic adenovirus (OAd) by inserting expression cassettes of therapeutic transgenes into the OAd genome is a promising approach to enhance the therapeutic effects of an OAd. Ideally, this approach would simultaneously promote the replication of an OAd in tumor cells and transgene product-mediated antitumor effects by expressing therapeutic transgenes. We previously demonstrated that knockdown of cullin 4A (CUL4A), which is an E3 ubiquitin ligase, significantly promoted adenovirus replication by increasing the c-JUN protein level. In addition, previous studies reported that CUL4A was highly expressed in various types of tumor, and was involved in tumor growth and metastasis. Materials and Methods: In this study, we developed a novel OAd expressing a short-hairpin RNA (shRNA) against CUL4A (OAd-shCUL4A). Results: OAd-shCUL4 mediated higher levels of cytotoxic effects on various types of human tumor cell than a conventional OAd. Higher levels of OAd genome copy numbers were found in the tumor cells for OAd-shCUL4A, compared with a conventional OAd. Conclusion: OAd-shCUL4A showed efficient antitumor effects by both enhancing OAd replication and inhibiting tumor cell growth. ER -