AllTrans-Retinoic Acid Mediates MED28/HMG Box-Containing Protein 1 (HBP1)/β-Catenin Signaling in Human Colorectal Cancer Cells

Abstract

Vitamin A is required for normal body function, including vision, epithelial integrity, growth, and differentiation. All trans-retinoic acid (ATRA), a family member of vitamin A, has been explored in treating acute promyelocytic leukemia and other types of cancer. Dysregulated Wnt/β-catenin signaling and disrupted cadherin-catenin complex often contribute to colorectal malignancy. MED28, a mammalian Mediator subunit, is found highly expressed in breast and colorectal cancers. Our laboratory has also reported that MED28 regulates cell growth, migration, and invasion in human breast cancer cells. In the current study we investigated the effect of ATRA on MED28 and Wnt/β-catenin signaling in colorectal cancer. HCT116, HT29, SW480, and SW620, four human colorectal cancer cell lines representing different stages of carcinogenesis and harboring critical genetic changes, were employed. Our data indicated that regardless of genetic variations among these cells, suppression of MED28 reduced the expression of cyclin D1, c-Myc, and nuclear β-catenin, but increased the expression of E-cadherin and HMG box-containing protein 1 (HBP1) where HBP1 has been described as a negative regulator of the Wnt/β-catenin signaling. The reporter activity of an HBP1 promoter increased upon MED28 knockdown, but decreased upon MED28 overexpression. ATRA reduced the expression of MED28 and mimicked the effect of MED28 suppression in down-regulating Wnt/β-catenin signaling. Taken together, ATRA can reverse the suppressive effect of MED28 on HBP1 and E-cadherin and inactivate the Wnt/β-catenin pathway in colorectal cancer, suggesting a protective effect of ATRA against colorectal cancer. J. Cell. Physiol. 231: 1796-1803, 2016. © 2015 Wiley Periodicals, Inc.

MED28 and forkhead box M1 (FOXM1) mediate matrix metalloproteinase 2 (MMP2)‐dependent cellular migration in human nonsmall cell lung cancer (NSCLC) cells

“…In addition to NSCLC, our group has previously identified a role of MED28 in the malignancy of breast cancer as indicated by its effect on migration and invasion, as well as cell morphology of human breast cancer cells (Huang et al, ; Huang et al, ). Moreover, we have also reported that MED28 is involved in cell growth in both human breast cancer cells and colorectal cancer cells (Huang et al, ; Lee et al, ). Our findings further emphasize the significance of MED28 and imply the prospective translational application of MED28 in tumorigenesis and cancer development.…”

“…For example, the expression of Mediator subunit MED15 with its clinical implications in head and neck squamous cell carcinoma has been identified (Shaikhibrahim et al, ). Recently, we have reported that MED28, another Mediator subunit, is involved in cell growth in human breast cancer cells and colorectal cancer cells (Huang et al, ; Lee, Hsieh, Huang, & Li, ). Therefore, mammalian Mediator subunits display novel cellular roles in addition to their function in transcriptional activation.…”

Long noncoding RNA actin filament‐associated protein 1 antisense RNA 1 promotes malignant phenotype through binding with lysine‐specific demethylase 1 and repressing HMG box‐containing protein 1 in non‐small‐cell lung cancer

“…HMG box‐containing protein 1 is a member of the HMG‐box transcription factor family and functions as a transcriptional repressor. It has two important domains including the HMG box DNA‐binding domain and an AXH domain . HMG box‐containing protein 1 has been found to have tumor‐suppressive functions in multiple cancers.…”

“…G, Relationship between AFAP1-AS1 and HBP1 expression was analyzed in the profile of non-small-cell lung cancer patient tissue from Gene Expression Omnibus domain and an AXH domain. 35 HMG box-containing protein 1 has been found to have tumor-suppressive functions in multiple cancers. For instance, HBP1 overexpression sensitizes prostate cancer cells to radiation and increases apoptosis in prostate cancer cells.…”

MiRNAs are Unlikely to be Involved in Retinoid Receptor Gene Regulation in Pancreatic Cancer Cells

“…The fact that the retinoid receptor genes are not mutated in the majority of human cancer specimens indicates that epigenetic events could be involved. Studies have reported that RARβ can be repressed by hypermethylation and histone deacetylation in some types of cancer, resulting in an associated resistance to the growth inhibitory effects of retinoic acid in some cancer types [35][36][37].…”