FOXQ1 Is Overexpressed in Colorectal Cancer and Enhances Tumorigenicity and Tumor Growth

Abstract

Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family, and it has recently been proposed to participate in gastric acid secretion and mucin gene expression in mice. However, the role of FOXQ1 in humans and especially in cancer cells remains unknown. We found that FOXQ1 mRNA is overexpressed in clinical specimens of colorectal cancer (CRC; 28-fold/colonic mucosa). A microarray analysis revealed that the knockdown of FOXQ1 using small interfering RNA resulted in a decrease in p21 CIP1/WAF1 expression, and a reporter assay and a chromatin immunoprecipitation assay showed that p21 was one of the target genes of FOXQ1. knockdown of H1299/FOXQ1 cells increased tumor growth, suggesting that FOXQ1 promotes tumor growth independent of p21. Microarray analysis of H1299/EGFP and H1299/FOXQ1 revealed that FOXQ1 overexpression upregulated several genes that have positive roles for tumor growth, including VEGFA, WNT3A, RSPO2, and BCL11A. CD31 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining of the tumor specimens showed that FOXQ1 overexpression mediated the angiogenic and antiapoptotic effect in vivo. In conclusion, FOXQ1 is overexpressed in CRC and enhances tumorigenicity and tumor growth presumably through its angiogenic and antiapoptotic effects. Our findings show that FOXQ1 is a new member of the cancer-related FOX family.

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas

“…threshold above which the test outcome was deemed to be positive. qPCR published microarray expression studies in which signals from the same probe sets were substantially elevated in CRC, 18 in colorectal adenoma, 19 and even in macroscopically normal-looking colonic mucosa from CRC patients. 20 In those studies, the observations had not been investigated further.…”

FGF3/FGF4 amplification and multiple lung metastases in responders to sorafenib in hepatocellular carcinoma

“…To evaluate growth inhibition in the presence of various concentrations of sorafenib, we used an MTT assay as described. 12 Plasmid Construction, Viral Production, and Stable Transfectants. The methods used in this section have been described.…”

“…The methods used in this section have been described. 12 The complementary DNA fragment encoding human full-length FGF3 or FGF4 was isolated using PCR and Prime STAR HS DNA polymerase (TaKaRa, Otsu, Japan) with following primers: FGF3, 5 0 -GG GAA TTC GCC GCC ATG GGC CTA ATC TGG CTG CTA-3 0 (forward) and 5 0 -CC CTC GAG GCC CAG CTA GTG CGC ACT GGC CTC-3 0 (reverse); FGF4, 5 0 -GG GAA TTC GCC GCC ATG TCG GGG CCC GGG ACG GCC GCG GTA GCG C-3 0 (forward) and 5 0 -CC CTC GAG GGA GGG TCA CAG CCT GGG GAG GAA GTG GGT GAC CTT C-3 0 (reverse). The stable transfectants expressing EGFP or FGF3 or FGF4 for each cell line were designated as A549/EGFP, A549/FGF3, and A549/FGF4.…”

Expression changes in arrestin β 1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients

“…The microarray procedure was performed according to the Affymetrix protocols (Santa Clara, CA), as described previously (13). Briefly, cRNA was synthesized using the GeneChip ® 3'-Amplification Reagents One-Cycle cDNA Synthesis Kit (Affymetrix).…”