DRAGO (KIAA0247), a New DNA Damage–Responsive, p53-Inducible Gene That Cooperates With p53 as Oncosuppressor

Abstract

DRAGO represents a new p53-dependent gene highly regulated in human cells and whose expression cooperates with p53 in tumor suppressor functions.

KIAA0247 inhibits growth, migration, invasion of non‐small‐cell lung cancer through regulating the Notch pathway

“…KIAA0247 expression is suggested to be regulated by the tumor suppressor p53 and thus may be involved in carcinogenesis. Previous studies have shown that low KIAA0247 mRNA levels in feces strongly correlate with colorectal tumor size and poor prognosis and that KIAA0247 expression inversely correlates with tumor stage in ovarian cancer and histological grade in glioma . Therefore, we hypothesized that KIAA0247 may also play an important role in the progression of NSCLC.…”

“…In KIAA0247 knockdown experiments, cells were transfected with KIAA0247 ‐specific siRNA and scrambled control siRNA (GenePharma, Shanghai, China) for 48 hours. For KIAA0247 overexpression, cells were transfected with a KIAA0247 expression plasmid and the corresponding empty pCNA3.0 vector, which were kindly donated by Massimo Broggini (Istituto di Ricerche Farmacologiche, Ranica, Italy) …”

“…KIAA0247 is a novel gene encoding a 303‐amino acid single‐pass type I membrane protein, which is highly conserved among species. Although KIAA0247 is not mutated in cancers, it has been suggested to play a role in oncogenesis because of a p53‐responsive element found in its promoter region, indicating that KIAA0247 is a prospective target for the tumor suppressor p53 . KIAA0247 has also been named DRAGO (drug‐activated gene overexpressed) because treatment with certain drugs (cisplatin, alkylating agents, antimetabolites, topoisomerase II inhibitors, taxanes, and nutlin‐3) induces its expression in HCT116 p53 +/+ cells but not in HCT116 p53 −/− cells .…”

“…Although KIAA0247 is not mutated in cancers, it has been suggested to play a role in oncogenesis because of a p53‐responsive element found in its promoter region, indicating that KIAA0247 is a prospective target for the tumor suppressor p53 . KIAA0247 has also been named DRAGO (drug‐activated gene overexpressed) because treatment with certain drugs (cisplatin, alkylating agents, antimetabolites, topoisomerase II inhibitors, taxanes, and nutlin‐3) induces its expression in HCT116 p53 +/+ cells but not in HCT116 p53 −/− cells . KIAA0247 overexpression is associated with the therapeutic benefits of 5‐fluorouracil, and the presence of KIAA0247 mRNA in fecal samples of colon cancer patients correlates with a more favorable prognosis .…”

“…KIAA0247 overexpression is associated with the therapeutic benefits of 5‐fluorouracil, and the presence of KIAA0247 mRNA in fecal samples of colon cancer patients correlates with a more favorable prognosis . In ovarian cancer, advanced‐stage tumors express approximately 30% less KIAA0247 mRNA compared to levels in early‐stage tumors . Another study showed that KIAA0247 mRNA was downregulated in glioma compared to normal brain tissue, whereas KIAA0247 overexpression suppressed the proliferation and angiogenesis of glioma cell lines and promoted apoptosis through inactivation of the AKT and Stat3 signaling pathways .…”