title: APRIL depletion induces cell cycle arrest and apoptosis through blocking TGF-β1/ERK signaling pathway in human colorectal cancer cells.
abstract: It is well documented that a proliferation-inducing ligand (APRIL), a newly found member of tumor necrosis factor superfamily, overexpressed in the majority of malignancies, plays a potential role in the occurrence and development of these tumors. Herein, we demonstrated that APRIL depletion by using RNA interference in human colorectal cancer (CRC) COLO 205 and SW480 cells resulted in cell proliferation inhibition and evoked cell cycle arrest in G0/G1 phase and apoptosis, coupled with decrease in CDK2, Cyclin D1, Bcl-2 expression and an increase of p21 and Bax expression. In addition, the decreased expression of transforming growth factor-β1 (TGF-β1) and p-ERK was also showed in siRNA-APRIL transfected COLO 205 and SW480 cells, whereas the protein expression levels of Smad2/3, p-Smad2/3, and ERK were not significantly changed. Taken together, our results indicate that APRIL depletion induces cell cycle arrest and apoptosis partly through blocking noncanonical TGF-β1/ERK, rather than canonical TGF-β1/Smad2/3, signaling pathway in CRC cells. Moreover, our study highlights APRIL as a potential molecular target for the therapy of CRC.
authors.affiliation: Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, School of Public Health, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ni
authors.forename: Guihua
authors.initials: G
authors.lastname: Wang
authors.forename: Weifeng
authors.initials: W
authors.lastname: Ding
authors.forename: Hui
authors.initials: H
authors.lastname: Cong
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Ju
authors.forename: Shumei
authors.initials: S
authors.lastname: Yang
authors.forename: Huimin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; C114631:TNFSF13 protein, human; D053773:Transforming Growth Factor beta1; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13