Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

Abstract

Abstract. Inhibitor of DNA-binding protein 1 (ID1) is commonly abnormally overexpressed in colorectal cancer (CRC); yet, the functional significance of ID1 in the growth and invasive properties of CRC cells remains largely unclear. The present study investigated the effects of ID1 downregulation on the cell growth and metastatic features of CRC. Using lentiviral shRNA infection, stable ID1-knockdown (KD) HCT116 and SW620 cells, human metastatic CRC cell lines, were created. In vitro, the migration/invasion capacity of the ID1-KD CRC cells was assessed by a wound healing assay. The activities of MMP2 and MMP-9 were measured by gelatin zymography. The expression of CXC chemokine receptor 4 (CXCR4), PCNA and survivin were determined by immunoblot analysis and qRT-PCR. The effects of ID1 knockdown on tumor growth and hepatic metastasis were demonstrated by a xenograft study in mice. The results showed evident decreases in proliferation, migration and invasion and an increased apoptosis rate in the ID1-KD CRC cells. Similarly, ID1 knockdown significantly decreased mRNA and protein levels of PCNA, survivin, CXCR4, MMP2 and MMP9. Overexpression of CXCR4 antagonized the negative effect on the migration and invasion abilities of the ID1-KD cells. As compared with the control, ID1 knockdown prevented tumor growth and profoundly suppressed hepatic metastasis in vivo. The present study demonstrated the significance of ID1 in colon cancer progression, and its effect on tumor invasiveness and metastatic properties may be partly dependent on CXCR4.

Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels

“…ID1 is an inhibitor of DNA binding that interacts and inhibits the transcriptional activation ability of basic HLH proteins which leads to tumour growth and angiogenesis [45]. Knockdown of ID1 has been shown to significantly decrease mRNA and protein levels of survivin in colorectal cancer cells [46] as well as to remove survivin inhibition of apoptosis in head and neck squamous cell carcinoma [47]. BIRC5 encodes the expression of anti-apoptotic protein survivin and elevated activity of this survival cascade has been implicated in cancer cell survival and disease progression [48,49,50].…”

siRNA-mediated knockdown of ID1 disrupts Nanog- and Oct-4-mediated cancer stem cell-likeness and resistance to chemotherapy in gastric cancer cells

“…Numerous studies have highlighted the complex role served by members of the ID subfamily in mammalian cell fate determination (21,27,28,34). IDs are involved in numerous biological processes, including the inhibition of differentiation, and the maintenance of self-renewal and multipotency in stem cells (22,23).…”

Study of As 2 O 3 regulating proliferation and apoptosis of Tca8113 cells by inhibiting the expression of Id-1

“…Li et al [18] found that ectopic expression of Id-1 could regulate the cell cycle, promote cell proliferation and metastasis, while down-regulation of Id-1 expression had the opposite effect. Lai et al [19] used RNAi technology to knock down Id-1 expression in colorectal cancer cells. It was found that the cell proliferation ability decreased, the number of migration and invasion cells decreased significantly, and the expression of matrix metalloproteinase-2 decreased.…”