Knockdown of the novel proteasome subunit Adrm1 located on the 20q13 amplicon inhibits colorectal cancer cell migration, survival and tumorigenicity.
The novel proteasome subunit Adrm1 located on the 20q13 amplicon was differentially expressed in colorectal cancer by semiquantitative RT-PCR. Adrm1 mRNA was overexpressed in 46.2% (18/39) colorectal cancer tissues compared to their matched normal mucosa and significantly correlated with lymph node metastasis of colorectal cancer (P=0.037). Knockdown of Adrm1 by shRNA in human colon carcinoma RKO cells inhibited their anchorage-independent growth, cell migration as well as cell proliferation through inducing apoptosis and cell cycle arrest at the G1 phase. In addition, stable RNA interference of Adrm1 gene synergistic with 5-Fu treatment suppressed RKO cell growth in vitro. Collectively, these data suggested that Adrm1 is potentially oncogenic and may play an important role in colon tumorigenesis. Regiment with combined application of Adrm1 RNA interference and chemotherapy may emerge as a novel therapeutic strategy for Adrm1 overexpressed colorectal cancer.
Chen
Wei
W
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Zhejiang 310016, People's Republic of China.
Hu
Xiao-Tong
XT
Shi
Qing-Lan
QL
Zhang
Fu-Biao
FB
He
Chao
C
D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C500781:ADRM1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D046988:Proteasome Endopeptidase Complex