The homeobox genes (HOX) have emerged as a new family of master regulators of development and cancer. In the current study, we examined the expression and function of HOXC10 in human non-small cell lung cancer (NSCLC). We observed increased expression of HOXC10 in the more aggressive human NSCLC cell line NCI-H23 over the well differentiated A549 cells. To elucidate the expression and function of HOXC10 in NSCLC cells, we employed RT-PCR, immunoblotting, methylation-specific PCR, apoptosis assays, and xenograft model. Overexpression of HOXC10 in A549 cells conveyed increased proliferation, reduced apoptosis, and accelerated tumor growth when transplanted into nude mice. In contrast, siRNA-mediated knockdown of HOXC10 in NCI-H23 cells reduced proliferation and increased apoptosis. Our results further indicated that hypomethylation of the CpG island in the HOXC10 promoter was critical to elevated expression of HOXC10 in NSCLC cells. Lastly, we identified a G-quadruplex in the HOXC10 promoter and its G-quadruplex formation was required for elevated expression of HOXC10 in NSCLC cells. Moreover our results suggest that disruption of G-quadruplex formation can silence HOXC10 expression in NSCLC cells. In summary, we report HOXC10 as a novel tumor promoting oncogene in NSCLC cells.
Keywords: CpG island; G-quadruplex; HOXC10; cytosine methylation; non-small cell lung cancer.