<p>HOPX Is an Epigenetically Inactivated Tumor Suppressor and Overexpression of HOPX Induce Apoptosis and Cell Cycle Arrest in Breast Cancer</p>

Abstract

Background: Evidence has been shown that abnormal DNA methylation plays a vital role in the progression of breast cancer via silencing of gene expression. The results of bisulfite sequencing showed that the methylation status of HOPX in breast cancer tissues was higher than that in normal breast cancer tissues, but little known about the biological functions of HOPX in breast cancer. Methods: A total of 13 paired breast cancer and adjacent noncancerous tissues were subjected to bisulfite sequencing. Meanwhile, the methylation levels of cg218995965 and cg24862548 in breast cancer cells were detected by methylation-specific PCR (MSP). Flow cytometry, wound healing and transwell invasion assays were used to detect the apoptosis, migration and invasion in breast cancer cells. In addition, the expressions of HOPX, p21, cyclin D1 and CDK4 in cells were detected with Western blot assay. Results: Bisulfite sequencing indicated that the CpG sites (cg218995965 and cg24862548) in the HOPX promoter region showed significantly higher methylation in breast cancer tissues. In addition, methylation-specific PCR revealed that HOPX was significantly hypermethylated in breast cancer cell lines MDA-MB-468 and MCF-7. Furthermore, overexpression of HOPX significantly inhibited the proliferation of MDA-MB-468 and MCF-7 cells via inducing the apoptosis. Moreover, upregulation of HOPX markedly inhibited the migration and invasion abilities of MDA-MB-468 cells. Meanwhile, overexpression of HOPX obviously induced cell cycle arrest in MDA-MB-468 cells via upregulation of p21, and downregulation of cyclin D1 and CDK4. Additionally, overexpression of HOPX suppressed tumor growth of breast cancer in vivo. Conclusion: Our data showed that HOPX, a tumor suppressor, is epigenetically silenced in breast cancer. Overexpression of HOPX could suppress the progression of breast cancer, and thus indicating that it might serve as a potential target for the treatment of patients with breast cancer.

HOPX: A Unique Homeodomain Protein in Development and Tumor Suppression

“…HOPX is epigenetically silenced in breast cancer. HOPX overexpression causes apoptosis and cell cycle arrest in breast cancer cells, suggesting that it could be utilized as a therapeutic target for breast cancer patients [ 72 ].…”

FRL: An Integrative Feature Selection Algorithm Based on the Fisher Score, Recursive Feature Elimination, and Logistic Regression to Identify Potential Genomic Biomarkers

“…CRISP3 induces the abundant changes in the cell adhesion protein subsets Lasp1 and TJP1 , which are included both in in vitro and in vivo environments, and CRISP3 can therefore promote the development of tumors in the prostate [ 49 ]. The overexpression of HOPX , upregulation of p21, and downregulation of cyclin D1 and CDK4 regulate the progress of migration and invasion of MDA-MB-468 cells to modulate tumor growth of the breast [ 50 ]. Colorectal cancer (CRC) is an example where the expression of SPRR3 promotes the binding between PCAT18 and miR-759 and therefore restores a portion of the proliferation and invasion capabilities of CRC cells [ 51 ].…”