Abstract
Melanoma-associated antigen family A (MAGE-A) is a family of cancer/testis antigens that are expressed in malignant tumors but not in normal tissues other than the testes. MAGE-A12 is a MAGE-A family gene whose tumorigenic function in cancer cells remains unclear. Searches of the Oncomine and NextBio databases revealed that malignant tumors show up-regulation of MAGE-A12 mRNA relative to corresponding normal tissue. In PPC1 primary prostatic carcinoma cells and in HCT116 colorectal cancer cells (wild type and p53-depleted), MAGE-A12 gene knockdown using siRNA or shRNA diminishes cancer cell proliferation as assessed by cellular ATP levels, cell counting, and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content show that MAGE-A12 knockdown causes G2/M arrest and apoptosis. In tumor xenografts of HCT116 cells, conditional knockdown of MAGE-A12 suppresses tumor growth. The depletion of MAGE-A12 leads to the accumulation of tumor suppressor p21 in PPC1, HCT116, and p53-depleted HCT116 cells. Conversely, CDKN1A knockdown partially rescues the viability of PPC1 cells transfected with siRNA targeting MAGE-A12, while p21 overexpression leads to proliferation arrest in PPC-1 cells. Furthermore, exogenous MAGE-A12 expression promotes the ubiquitination of p21. Our findings reveal that MAGE-A12 plays crucial roles in p21 stability and tumor growth, suggesting that MAGE-A12 could provide a novel target for cancer treatment.
Highlights
The melanoma-associated antigen (MAGE) protein family is a large, highly conserved group of proteins that share a MAGE homology domain [1]
To assess the role of MAGE-A12 in normal tissues and cancers, we examined a public database to evaluate the levels of MAGE-A12 expression
The NextBio database, a The Cancer Genome Atlas (TCGA) database containing information on MAGE-A12 RNA expression levels, showed MAGE-A12 to be an up-regulated gene in cancers, relative to corresponding normal tissue (Supplementary Figure 2A)
Summary
The melanoma-associated antigen (MAGE) protein family is a large, highly conserved group of proteins that share a MAGE homology domain [1]. The human MAGE family proteins can be divided into two groups based on expression pattern. Type I MAGE proteins are cancer/ testis antigens and include the MAGE-A, -B, and -C subfamilies, which are clustered on the X-chromosome. Type II MAGE proteins are expressed throughout tissues and are not limited to the X chromosome [1]. Members of melanoma-associated antigen family A (MAGE-A) are expressed in a wide variety of malignant tumors but not in normal adult tissues other than the testes [2].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
