Association of AlkB homolog 3 expression with tumor recurrence and unfavorable prognosis in hepatocellular carcinoma.

Abstract

The mammalian AlkB homolog protein family has been reported to promote tumor cell invasion and metastasis of human cancer. However, the expression status and clinical significance of AlkB homolog 3 (ALKBH3) in hepatocellular carcinoma (HCC) have not been reported yet. In the present study, we investigated the protein expression of ALKBH3 by immunohistochemistry assay and evaluated its association with tumor progression, recurrence, and prognosis in 272 patients with HCC. In addition, we explored ALKBH3 function via gene overexpression and knockdown of ALKBH3. AlkB homolog 3 was overexpressed in HCC compared with adjacent non-tumorous specimens. Moreover, ALKBH3 expression was closely related to tumor differentiation and tumor-node-metastasis stage. Interestingly, the ALKBH3 high expression in tumor tissues of HCC patients had more poor disease-free survival and overall survival than low-expression patients. Consistently, we found that knockdown of ALKBH3 inhibits HCC cell proliferation in vitro and xenograft tumor formation in vivo and overexpressing ALKBH3 showed the opposite results. ALKBH3 knockdown may inhibit cell proliferation, presumably through p21/p27-mediated cell-cycle arrest at G1 phase in human HCC. ALKBH3 may also play some role on chemosensitivity to certain genotoxic reagents, such as cisplatin (CDDP) and epirubicin. These findings reveal an important role of ALKBH3 in HCC, indicating that ALKBH3 could be used as a new therapeutic target in future.