The Functional Study Of ADRM1 Located On 20q13 Amplicon In Colorectal Cancer Development

Colorectal cancer(CRC) is one of the most common causes of cancer-related deaths throughout the world.Karyotypic/cytogenetic data regarding CRC have been accumulated over the last 10 years,and a gain of 20q,especially the 20q13 region,was frequently reported as a common genetic aberration.The novel proteasome subunit ADRM1(GeneID:11047 ) located on the 20q13 amplicon was differentially expressed in colorectal cancer and paired normal bowel wall by semiquantitative RT-PCR based on the tissue bank generated in our center.ADRM1 mRNA were overexpressed in 46.2%colorectal cancer tissues compared to their matched normal mucosa and significantly correlated with lymph node metastasis of colorectal cancer.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;in addition,given to the close relationship between ADRM1 and ubiquitin-proteasome system,our study provided a new target for proteasome inhibitor design.