title: CUL4A promotes proliferation and metastasis of colorectal cancer cells by regulating H3K4 trimethylation in epithelial-mesenchymal transition.
abstract: Increasing evidence suggests that CUL4A, a ubiquitin ligase, is involved in the promotion of cancer malignancy and correlated with worse clinical prognosis in several kinds of human cancers. Although its effect and mechanism on the progression of colorectal cancer (CRC) remain unknown. Our clinical data show that CUL4A protein is overexpressed, positively associated with lymph nodes status, differentiation degree, tumor size, and poor prognosis in 80 CRC patients. CUL4A overexpression promotes cell proliferation and colony formation of CRC cells. Knockdown of CUL4A inhibits cell proliferation and migration. CUL4A can significantly promote the in vitro migration of CRC cells via induction of the epithelial-mesenchymal transition process. And the modulation of CUL4A expression altered the level of H3K4 trimethylation at the E-cadherin, N-cadherin, and vimentin gene promoters, which in turn transcriptionally regulated their expression. Moreover, knockdown of CUL4A also decreased the tumor volume and tumor weight in vivo. Together, our results reveal that CUL4A plays as an oncogene in CRC and may become a potential therapeutic target in the treatment of colorectal cancer.
authors.affiliation: Clinical Laboratory, The First Affiliated Huai'an Hospital of Nanjing Medical University.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Sui
authors.affiliation: Huai'an No 4 People's Hospital, Huai'an.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Digestive System, Jiangsu Province Hospital of TCM, Nanjing.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang.
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
authors.affiliation: Geriatric Department, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an.
authors.forename: Sumei
authors.initials: S
authors.lastname: Fan
authors.affiliation: Clinical Laboratory, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
keywords: CUL4A; EMT; H3K4 trimethylation; colorectal cancer; migration