CD59 is overexpressed in human lung cancer and regulates apoptosis of human lung cancer cells

Abstract

CD59, belonging to membrane complement regulatory proteins (mCRPs), inhibits the cytolytic activity of complement and is overexpressed in many types of solid cancers. The aim of the present study was to detect the expression of CD59 in non-small cell lung cancer (NSCLC) and to investigate the relationship between decreased CD59 expression and tumorigenesis of NSCLC by transfecting recombinant retrovirus encoding shRNA targeting human CD59 into the human NSCLC cell line NCI-H157. CD59 expression in NSCLC was detected by immunocytochemistry (IHC). In the human NSCLC cell line NCI-H157, CD59 mRNA and protein expression suppressed with lentivirus-mediated RNAi was confirmed by using RT-PCR and western blotting, respectively. The proliferation and apoptosis of NCI-H157 cells was measured by using MTT assay and FACS. The resistance to complement cracking ability was detected by LDH assay. Caspase-3 expression in cells was assessed by IHC. Bcl-2 and Fas protein was determined by western blotting both in vitro and in vivo. CD59 is overexpressed in human NLCLC cancer. In NCI-H157 cells, lentivirus-mediated RNAi significantly reduced both CD59 mRNA and protein expression, which resulted in suppressing cell proliferation and increasing cell apoptosis. When incubated with fresh normal human serum (8%, v/v) for 1 h at 37˚C, the cell viability was decreased and cell apoptosis was increased in siCD59-infected NCI-H157 cells compared to siCD59-C-infected cells. Reduced CD59 expression led to increased expression of caspase-3 and Fas and decreased expression of Bcl-2. Furthermore, the nude mouse tumor graft weight was significantly decreased and survival rate was significantly increased in the siCD59 group. CD59 is overexpressed in human NLCLC. CD59 silencing in NSCLC cancer cells via retrovirus-mediated RNAi can enhance complement-mediated cell apoptosis, inhibiting the growth of NSCLC. CD59 may serve as a potential target for gene therapy in NSCLC.

The membrane complement regulatory protein CD59 promotes tumor growth and predicts poor prognosis in breast cancer

“…In addition, CD59 overexpression protects MCF-7 breast cancer cells from complement-mediated cytolysis and promotes MCF-7 cell proliferation by inhibiting BCL-2 expression; conversely, CD59 knockdown upregulates Fas and caspase-3 to induce apoptosis (20). Besides, CD59 silencing in NSCLC cancer cells can enhance complement-mediated cell apoptosis and inhibit the growth of NSCLC (16), which shows accordance with our study.…”

“…To escape complement attack, tumor cells express high levels of membrane complement regulatory proteins (mCRPs) (13 3,4,6 , RONGCHENG LUO 5 and ZHIMING SHAO complement activation, is considered to be the most effective mCRP at protecting cancer cells by inhibiting MAC formation (14). CD59 is widely expressed, and its expression levels are higher in almost all cancer cells than in adjacent normal cells (14)(15)(16), which facilitates tumor cell escape from complement attack (17,18). Although previous reports have described CD59 as a prognostic biomarker in breast cancer (19)(20)(21) playing important roles in immunotherapy of human malignancies (22), the role of CD59 in breast cancer growth and prognosis has not been fully elucidated.…”

A Systematic Analysis Reveals Heterogeneous Changes in the Endocytic Activities of Cancer Cells

“…Although markers for clathrin- and caveolae-independent endocytotic pathways are less well characterized, glycophosphatidylinositol-anchored proteins (GPI-AP) are reportedly internalized by these routes (15, 17, 18). For our studies, we chose complement lysis restricting factor/CD59 (31), a GPI-AP that is involved in cellular processes critical to lung cancer cell survival and internalized via CIE (32, 33). Recent studies have identified the transmembrane glycoprotein, CD44, which is a hyaluronic acid receptor, as a cargo molecule specifically internalized by CLICs and recycled via GPI-enriched endocytic compartments (GEEC; refs.…”

Alternative Polyadenylation of Tumor Suppressor Genes in Small Intestinal Neuroendocrine Tumors

“…Interestingly, four genes out of the nine with UTR-APA have been found to be either overexpressed in cancer: PSMD8 (27), CD59 (29), and SRSF5 (32) or is suggested to be overexpressed: ANKH (30). The UTR-APA in these genes produces mRNA isoforms that lack one or more target sites for miRNAs present in SI-NETs.…”