Zhao Hongyan, Zhao Dali, Tan Gang, Liu Yong, Zhuang Liwei, Liu Tiefu
Department of Gastroenterology, The Fourth Affiliated Hospital of Harbin Medical University Harbin, China ; Department of Gastroenterology, The Fourth Hospital of Harbin Harbin, China.
Department of General Surgery, The First Affiliated Hospital of Harbin Medical University Harbin, China.
Int J Clin Exp Med. 2015 Mar 15;8(3):3420-8. eCollection 2015.
Bufalin is used to treat many patients with solid malignant tumors clinically. Bufalin could induce gastric cancer cell apoptosis via BAX. microRNA (miRNA) plays important roles in gene regulation. However, miRNA involving in bufalin inducing apoptosis of gastric cancer cells remains to futher research. To study the regulatory role of miRNA in bufalin induced cancer cell apoptosis. Firstly, we verifed that bufalin could induce gastric cancer cell apoptosis by inducing BAX expression. miR-298 was predicted as a regulator of BAX and further study verified Bax was a target gene of miR-298 by luciferase reporter assay. miR-298 could down-regulate BAX on mRNA and protein level in gastric cancer cells. miR-298 promoted cell proliferation and inhibited apoptosis of gastric cancer cells. It was also found that bufalin inhibited cell proliferation and promoted cell apoptosis by down-regualtion of miR-298. In summary, bufalin-associated miR-298 may indirectly be involved in cell proliferation and apoptosis by targeting BAX, pointing to use as a potential molecular target in gastric cancer therapy.
蟾毒灵在临床上用于治疗许多实体恶性肿瘤患者。蟾毒灵可通过BAX诱导胃癌细胞凋亡。微小RNA（miRNA）在基因调控中发挥重要作用。然而，miRNA参与蟾毒灵诱导胃癌细胞凋亡仍有待进一步研究。为了研究miRNA在蟾毒灵诱导癌细胞凋亡中的调控作用。首先，我们证实蟾毒灵可通过诱导BAX表达诱导胃癌细胞凋亡。miR-298被预测为BAX的调节因子，进一步研究通过荧光素酶报告基因检测证实Bax是miR-298的靶基因。miR-298可在mRNA和蛋白质水平下调胃癌细胞中的BAX。miR-298促进胃癌细胞增殖并抑制其凋亡。还发现蟾毒灵通过下调miR-298抑制细胞增殖并促进细胞凋亡。总之，与蟾毒灵相关的miR-298可能通过靶向BAX间接参与细胞增殖和凋亡，提示其可作为胃癌治疗的潜在分子靶点。
