Novel mechanism underlying anticancer effect of methyltransferase inhibitor 5-aza-2′-deoxycytidine / 肿瘤

ABSTRACT

Objective: To reveal a novel mechanism by which 5-aza-2′- deoxycytidine (AZA) plays its anticancer role, and whether AZA can inhibit the expressions of cancer-associated genes by activating their antisense RNAs. Methods: Six genes were chosen from those having antisense RNAs, which were previously obtained by sequencing a double-stranded RNA library. The selected genes included phosphatase and tensin homolog deleted on chromosome ten (PTEN ), signal transducers and activators of transcription 1 (STAT 1), Ras-like proto-oncogene B (RALB ), MET, CD 44 and heat-shock protein A4 (HSPA 4). The human hepatocellular carcinoma HepG2 cells were treated with AZA (dissolved in DMSO) or DMSO (as the control). The expressions of sense and antisense RNAs for the selected genes were detected by strand-specific RT-PCR and real-time fluorescent quantitative PCR, respectively. Results: The antisense RNAs of all 6 genes were activated by AZA treatment (all P < 0.01). On the other hand, AZA also induced the expressions of tumor suppressor gene PTEN and innate immunity-related gene HSPA 4 (P < 0.01, P < 0.001). In contrast, the expressions of cancer-related genes, CD 44 and HSPA 4, were obviously inhibited by AZA treatment (both P < 0.01). Conclusion: AZA can activate the antisense RNAs, so as to promote the expressions of tumor suppressor genes and innate immunityrelated genes, but to inhibit the expressions of cancer-associated genes; which may be the novel mechanism underlying anticancer effect of AZA.